bluuebunny/crossref_metadata_2025 huggingface dataset:
Vessel, plaque, and lumen morphology after transluminal balloon angioplasty. Quantitative study in distended human arteries.
Authors: Lyon R T , Zarins C K , Lu C T , Yang C F , Glagov S
Published: June 2011

We performed transluminal balloon angioplasty in 24 cadaver and nine amputated limb superficial femoral arteries under controlled experimental conditions. The cadaver arteries were excised, restored to in situ length, redistended, and maintained at 100 mm Hg intraluminal pressure at 37 degrees C throughout the angiographic and dilation procedure and during fixation. The amputated limb arteries were dilated and pressure perfusion-fixed after dilation. Quantitative analysis of cadaver vessels revealed that arteries with prominent atherosclerotic lesions had the same internal elastic lamina (IEL) circumference (15.6 +/- 1.0 mm) as those with little or no stenosis (16.8 +/- 0.5 mm) but lumen area (8.8 +/- 1.7 mm2) was markedly reduced compared to nonstenotic sites (20.0 +/- 1.9 mm2, p less than 0.01). Lesions occupied 49 +/- 6% of the area circumscribed by the IEL in cadaver arteries with prominent plaques. After dilatation, lumen areas at stenotic sites were enlarged 43% on histologic sections (12.6 +/- 1.8 mm2 vs 8.8 +/- 1.7 mm2, p less than 0.01) and 31% as determined by angiography (p less than 0.05) when compared to immediately adjacent nondilated regions. The increased lumen area was associated with splitting of the intima near the edges of the plaque, separation of the edges of the plaque from the media, and stretching of the media and adventitia, often with accompanying rupture of the media. There was no evidence of plaque compression, fragmentation, deformation, modeling, or herniation into the media. The detached wedge-shaped edges of the lesions formed flaps projecting into the lumen, resulting in a marked increase in lumen irregularity on cross-section.(ABSTRACT TRUNCATED AT 250 WORDS)
Downregulation of high density lipoprotein receptor activity of cultured fibroblasts by platelet-derived growth factor.
Authors: Oppenheimer M J , Oram J F , Bierman E L
Published: June 2011

High density lipoprotein (HDL) receptor activity was decreased by the addition of platelet-derived growth factor (PDGF) to cholesterol-loaded cultured human skin fibroblasts. Effects were observed within 12 hours, coinciding with increases in tritiated thymidine incorporation into DNA. The PDGF-mediated decrease in HDL binding was associated with a decrease in cholesterol efflux promoted by HDL3. PDGF exerted reciprocal effects on HDL and low density lipoprotein (LDL) receptor activity. With fibroblasts not loaded with cholesterol, PDGF increased LDL binding without changing HDL receptor activity. With cholesterol-loaded cells, PDGF decreased HDL receptor activity without changing LDL receptor activity. These results show that a reduction in HDL receptor activity is an additional cellular response to PDGF. Decreased HDL-mediated cholesterol efflux may result in retention of cholesterol needed for membrane synthesis in cells stimulated to proliferate.
Glycosaminoglycans and apolipoproteins B and A-I in human aortas. Chemical and immunological analysis of lesion-free aortas from children and adults.
Authors: Ylä-Herttuala S , Solakivi T , Hirvonen J , Laaksonen H , Möttönen M , Pesonen E , Raekallio J , Akerblom H K , Nikkari T
Published: June 2011

To study changes in the contents of plasma lipoproteins in human arteries with age and the relationship of lipoproteins with other arterial constituents, we analyzed the contents of apolipoproteins B (apo B) and A-I (apo A-I), free and esterified cholesterol, and glycosaminoglycans (GAG) in lesion-free aortic intimas of 30 children and adults. The content of apo B increased significantly with age, whereas that of apo A-I remained relatively constant. Apo B and apo A-I had significant positive correlations with the content of chondroitin sulphates A + C (CS A + C), which comprised 35% to 47% of the aortic GAG. The correlations remained significant after correction for the effect of age. Aortic apo B, but not apo A-I, also showed significant positive correlations with the contents of intimal free and esterified cholesterol. The results indicate that: considerable amounts of apo B and apo A-I can be found in lesion-free aortic intimas; there is an age-related rise in the content of apo B and a fall in the ratio of apo A-I to apo B, which are unfavorable developments in the light of current views on atherogenesis; the contents of the apolipoproteins are proportional to that of CS A + C, which might have a role in the retention of lipoproteins in the arteries.
Production of plasminogen activators and inhibitor by serially propagated endothelial cells from adult human blood vessels.
Authors: van Hinsbergh V W , Binnema D , Scheffer M A , Sprengers E D , Kooistra T , Rijken D C
Published: June 2011

Endothelial cells were isolated from arteries and veins obtained from elderly people at autopsy and propagated for 37 to 69 population doublings. The cells secreted tissue-type plasminogen activator (t-PA) and PA inhibitor-1, and, after subculturing, urokinase-type PA (u-PA) antigen. The following differences between endothelial cells from adult arteries and veins were observed: 1) The cells had the potential to be propagated as a healthy monolayer. The diameter of aortic endothelial cells increased after 8 to 19 population doublings, while a homogeneous population of small diameter vena cava cells was retained for 35 population doublings. 2) The amount of secreted t-PA varied. Vena cava cells produced four times more t-PA than aorta cells, and 20-fold more than umbilical artery or vein endothelial cells. The t-PA mRNA content of vena cava cells did not exceed that of aorta cells, but was fourfold greater than that of umbilical cord endothelial cells. 3) The release of u-PA antigen varied. No u-PA antigen was detectable in conditioned medium of primary cultures of human aorta and vena cava endothelial cells or of early passage vena cava cells. After prolonged subculturing, vena cava cells started to secrete u-PA. Endothelial cells from aorta and other adult arteries, however, started secreting u-PA after one to four passages, parallel to the occurrence of enlarged endothelial cells. u-PA was present as a u-PA/inhibitor complex and as a single-chain u-PA. These differences may be developmentally related to their artery or vein origin or may reflect differences acquired during the "life history" of these blood vessels in vivo. Our data suggest that the release of u-PA antigen by human macrovascular endothelial cells can be used as an indicator of cell senescence.
Interleukin-1 inhibits the synthesis of von Willebrand factor in endothelial cells, which results in a decreased reactivity of their matrix toward platelets.
Authors: de Groot P G , Verweij C L , Nawroth P P , de Boer H C , Stern D M , Sixma J J
Published: June 2011

We have studied the influence of recombinant human and murine interleukin-1 (IL-1) on the synthesis and secretion of von Willebrand factor by human endothelial cells. Treatment of endothelial cells with IL-1 caused a decline in the steady-state level of von Willebrand factor mRNA in endothelial cells. This decline resulted in a decreased secretion to the culture medium, a decreased storage of von Willebrand factor in the Weibel-Palade bodies, and a decreased incorporation into the extracellular matrix. As a consequence of the decreased amount of von Willebrand factor in the extracellular matrix we have found a strongly impaired platelet adhesion to these matrices. When the matrices of IL-1-treated cells were incubated with purified von Willebrand factor, their ability to support platelet adhesion was restored. These results suggest that perturbation of endothelial cells by inflammatory mediators like IL-1 results in a decreased adhesion of platelets to the subendothelium owing to a diminished synthesis of von Willebrand factor.
Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. I. Characterization of cellular lipid metabolism.
Authors: Schmitz G , Robenek H , Beuck M , Krause R , Schurek A , Niemann R
Published: June 2011

The effects of the slow Ca++ channel blocker, nifedipine, and ACAT inhibitor, octimibate, on the cholesterol metabolism of cholesterol-loaded macrophages were compared. We demonstrated that apolipoprotein A-I containing high density lipoproteins (HDL) bind to specific receptor sites on macrophages, are internalized, take up cholesterol, and are then released from the cells as native lipoproteins. The ACAT inhibitor enhances HDL receptor activity and promotes HDL-mediated cholesterol efflux from cultured mouse peritoneal macrophages. In contrast, the Ca++ antagonist increases acetyl LDL-mediated cholesterol influx, abolishes the increase in HDL binding induced by cholesterol accumulation, enhances apo E synthesis, and promotes cholesterol efflux by a mechanism independent of the presence of HDL in the surrounding medium. Concomitantly, a decrease in nucleoside transporter activity, an increase in intracellular ATP hydrolysis, adenosine and cyclic AMP concentration, and a stimulation of the activities of acid and neutral cholesteryl ester hydrolase and ACAT indicated that protein kinase A-catalyzed phosphorylation reactions might be involved in the increase in cholesterol efflux. The Ca++ antagonist-induced efflux occurred only with lysosomal-associated cholesterol, while the ACAT inhibitor acted on the formation of cytoplasmic lipid droplets. The secreted lipoprotein particles contained 68% unesterified cholesterol and 21% phospholipids, 8% esterified cholesterol, and 3% triglycerides. The phospholipid components were: 72% phosphatidylcholine, 22% sphingomyelin, and 6% phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine. We conclude that macrophages release cholesterol in two ways: 1) an HDL-mediated release of unesterified cholesterol increasing upon ACAT inhibition, and 2) an HDL-independent secretion of cholesterol which can be amplified by Ca++ antagonists.
Atherosclerotic vascular disease in middle-aged, insulin-treated, diabetic patients. Association with endogenous insulin secretion capacity.
Authors: Rönnemaa T , Laakso M , Puukka P , Kallio V , Pyörälä K
Published: June 2011

The prevalence of atherosclerotic vascular disease (ASVD) and its risk factors were investigated in 263 insulin-treated diabetic patients, ages 45 to 64 years, who were older than 30 years when their diabetes was diagnosed. The patients were divided into two groups based on the degree of endogenous insulin secretion capacity: Group A: glucagon-stimulated plasma C-peptide less than 0.20 nmol/l and Group B: C-peptide greater than or equal to 0.20 nmol/l. The age-adjusted prevalence of definite myocardial infarction was significantly higher in Group B than in Group A (16.8% vs. 5.2%, p less than 0.01). A similar difference between Groups A and B was found for definite or possible coronary heart disease (54.6% vs. 32.9%, p less than 0.001) and stroke (9.3% vs. 2.0%, p less than 0.05). In multivariate analysis, high glucagon-stimulated plasma C-peptide level (greater than or equal to 0.20 nmol/l) was positively associated with definite or possible coronary heart disease independently of other cardiovascular risk factors. Our results indicate that among insulin-treated patients with a late onset of diabetes, the prevalence of ASVD is markedly higher in those with persistent endogenous insulin secretion (noninsulin-dependent diabetes) than in those with low or no insulin secretion (insulin-dependent diabetes).
Atherosclerosis of cynomolgus monkeys hyper- and hyporesponsive to dietary cholesterol. Lack of effect of vasectomy.
Authors: Clarkson T B , Alexander N J , Morgan T M
Published: June 2011

A moderately atherogenic diet was fed to young adult cynomolgus macaque males that were observed to be either hypo- or hyperresponsive to dietary cholesterol and who were randomized into groups to be either vasectomized or sham-vasectomized. The extent of atherosclerosis was found to be considerably greater at all arterial sites studied for the monkeys that were hyperresponsive to dietary cholesterol. The differences in atherosclerosis development among the hyperresponder monkeys occurred primarily in the proximal portions of the coronary arteries, the proximal and distal portions of the common carotid arteries, and only in the most proximal portions of the femoral arteries. There were no significant effects of vasectomy or sham vasectomy on atherosclerosis extent in either the hyper- or the hyporesponding groups, although there was a suggestion of somewhat larger lesions in the left circumflex coronary artery of hyperresponder monkeys that were vasectomized and somewhat smaller atherosclerotic lesions in the left common carotid arteries of vasectomized monkeys. The data presented here do not support our first report of worsened atherosclerosis among cynomolgus monkeys fed diets high in cholesterol. The findings of the current study are consistent with recent epidemiological studies of vasectomized and nonvasectomized human males.
Characteristics associated with apoprotein and lipoprotein lipid levels in middle-aged women.
Authors: Meilahn E N , Kuller L H , Stein E A , Caggiula A W , Matthews K A
Published: June 2011

Recent evidence indicates that measurement of apoproteins may enhance evaluation of coronary heart disease risk. The purpose of the present study was to identify factors associated with interindividual variation in apoproteins (apo) A-I, A-II, and B and lipoprotein lipid levels in 541 healthy premenopausal women, a random sample ages 42 to 50 taken from driver's license lists. The results of multivariate analyses that included alcohol intake, obesity, smoking, exercise, and age as predictor variables showed alcohol consumption to be strongly, positively related to apo A-I and A-II and smoking and obesity to have modest lowering effects on apo A-I. Concentration of the high density lipoprotein subfraction, HDL2c, however, was highly negatively related to body mass index, with alcohol intake and smoking each contributing about 5% to the variation. HDL3c had a similar relationship to obesity, alcohol, and smoking, but the magnitude of effect was much smaller than that for HDL2c. Thus, the concentration of cholesterol relative to protein found in HDL, particularly HDL2, was lower in overweight women and higher in women who reported alcohol intake. About 10% of variation in low density lipoprotein cholesterol (LDLc) was explained jointly by smoking, obesity, and alcohol intake compared with 15% of variation in apo B associated primarily with obesity (8%) and, to a lesser extent, with age and smoking. Physical activity was not independently associated with any of the lipoprotein lipid or apoprotein measures. In sum, results show that obese women exhibited reduced HDLc per mole of protein and that alcohol intake was linked to increased HDL particle number.(ABSTRACT TRUNCATED AT 250 WORDS)
Apolipoprotein B gene haplotypes. Association between Ag and DNA polymorphisms.
Authors: Ma Y H , Ladias J A , Bütler R , Schumaker V N , Antonarakis S E , Lusis A J , Heinzman C , Kwiterovich P O
Published: June 2011

Berg et al. (Clin Genet 1986;30:515-520) have reported that an Xba I DNA polymorphic site in exon 26 of the apolipoprotein (apo) B gene is associated both with the Ag(x/y) immunochemical polymorphism and with elevated serum lipoprotein levels. Ma et al. (Arteriosclerosis 1987;7:301-305) have reported that the same Xba I polymorphism is associated with a different immunochemical polymorphism, Ag(c/g). To extend and clarify these observations, we have determined the Ag and Xba I polymorphism for 106 individuals. We find that the Xba I restriction fragment length polymorphism is in linkage disequilibrium with both Ag(x/y) and Ag(c/g) loci; thus, all 31 Xba I(X1/X1) genotypes observed in this study are also Ag(y/y). All but one of 22 Xba I(X2/X2) genotypes are also Ag(g/g). For individuals homozygous at either two or three of these loci, it was possible to determine the haplotypes for 128 apo B alleles. Of the eight possible apo B haplotypes, only four were represented in this unambiguous subpopulation, although other minor haplotypes were present in the total population from which it was derived. The identification of major apo B haplotypes in human populations may simplify the search for significant correlations between certain apo B alleles and lipid levels and atherosclerosis.
Enhanced apolipoprotein E production with normal hepatic mRNA levels in the Watanabe heritable hyperlipidemic rabbit.
Authors: Rall C J , Hoeg J M , Gregg R E , Law S W , Monge J C , Meng M S , Zech L A , Brewer H B
Published: June 2011

The Watanabe heritable hyperlipidemic rabbit (WHHL) provides an experimental animal model for the low density lipoprotein (LDL) receptor defect present in patients homozygous for familial hypercholesterolemia (FH). Both WHHL rabbits and FH patients have a four- to sevenfold increase in plasma levels of apolipoprotein E (apo E). To determine the etiology for the elevated apo E concentrations, kinetic studies of radiolabeled apo E were conducted in WHHL and control New Zealand White (NZW) rabbits. The sites of apo E synthesis in the WHHL rabbit were evaluated by quantitating apo E mRNA levels in 12 tissues by dot-blot analysis of total RNA from each tissue with an apo E cDNA probe. Compared to the NZW rabbit, the WHHL rabbit had a twofold increase in the plasma apo E residence time, a fourfold increase in apo E production rate, and normal apo E mRNA levels in the liver and all other major apo E synthetic tissues. However, a fivefold increase in WHHL aortic apo E mRNA levels was observed. The elevated level of aortic apo E mRNA indicated a potential role for apo E in modulating atherogenesis in the WHHL rabbit. These results established that the increased plasma apo E in the WHHL rabbit was due to increased synthesis and delayed catabolism. Moreover, the fourfold increase in apo E synthesis with normal tissue apo E mRNA levels may reflect a translational or posttranslational regulation of apo E synthesis.
Oxidized low density lipoprotein stimulates prostacyclin production by adult human vascular endothelial cells.
Authors: Triau J E , Meydani S N , Schaefer E J
Published: June 2011

Interactions between vascular endothelium and low density lipoprotein (LDL) have been implicated in the development of atherosclerosis. The effect of normal and oxidized LDL (Ox-LDL) on prostaglandin release by cultured adult human saphenous vein endothelial cells was investigated. Ox-LDL induced a rapid release of prostacyclin (PGI2) to levels which were several-fold higher than those observed with control LDL. PGI2 release was concentration-dependent and was biphasic, with a first peak occurring within 30 minutes (followed by a decrease), and a second peak occurring after several hours of incubation. PGI2 production was inhibited by lipoprotein-depleted serum and by indomethacin, an antagonist of cyclooxygenase activity. These cells produced mainly PGF2 alpha, with some PGE2 and PGI2 when stimulated by the ionophore A23187 at confluency. However, among these prostanoids, mainly PGI2 was produced in response to Ox-LDL. The data indicate that Ox-LDL induces the production of PGI2 by human vascular endothelial cells. Since Ox-LDL is cytotoxic, this phenomenon may be a manifestation of an early response to injury.
Axial dependence of platelet-collagen interactions in flowing blood. Upstream thrombus growth impairs downstream platelet adhesion.
Authors: Sakariassen K S , Baumgartner H R
Published: June 2011

Vascular subendothelium and collagenous surfaces were exposed to flowing citrated blood. Platelet interactions with these surfaces were investigated at various axial distances from the upstream end of the exposed surfaces. A pronounced axial decrease in surface coverage with platelets and in thrombus dimensions was encountered on collagenous surfaces. This phenomenon was observed at shear rates of 200 to 2000 s-1, but was most pronounced at low shear rates (less than 650 s-1). After 5 minutes of perfusion at a shear rate of 650 s-1, 4.6 x 10(6) platelets were deposited on the most upstream 20 mm2 of the collagen surface, in contrast to 2.2 x 10(6) platelets/20 mm2 14 mm farther downstream. Depletion of von Willebrand factor and/or thrombospondin from the boundary layer of the blood flow was not responsible for this. Collagen-bound von Willebrand factor enhanced the surface coverage with platelets without affecting the axial decrement, while pretreatment of the collagen surface with thrombospondin had no effect at all. However, partial inhibition of thrombus growth by aspirin reduced the axial decrements, and less thrombogenic surfaces as human and rabbit subendothelium, which induced only a few small thrombi, produced virtually no axial differences in platelet adhesion. Raising the shear rate to 2600 s-1 also gave no axial differences in platelet-collagen adhesion; it did, however, give an axial increase in thrombus dimensions. This increase was neutralized after the addition of antibody against human platelet thrombospondin to the blood.(ABSTRACT TRUNCATED AT 250 WORDS)
Sulfated polysaccharides modulate effects of acidic and basic fibroblast growth factors on repair of injured confluent human vascular endothelium.
Authors: Klein-Soyer C , Beretz A , Cazenave J P , Wittendorp-Rechenmann E , Vonesch J L , Rechenmann R V , Driot F , Maffrand J P
Published: June 2011

Semi-automatic analysis of the repair process of a circular mechanical lesion of confluent human vascular endothelial cells in vitro was used to evaluate the contributions of cell migration and cell proliferation. Standard heparin added to culture medium that contained 30% human serum induced an inhibition of cell migration at the lesion margin during the first day after injury. Several sulfated polysaccharides were tested in the presence of 5% human serum. Standard heparin, low molecular weight heparin, or pentosan polysulfate markedly reduced the rate of lesion regeneration. Cell proliferation, measured by 3H-thymidine incorporation at the lesion margin, and cell migration were both decreased. In contrast, the combination of acidic fibroblast growth factor with a sulfated polysaccharide accelerated the repair process. Basic fibroblast growth factor combined with a sulfated polysaccharide gave a regeneration rate similar to that of the control; however, at 4 days after injury, the residual lesion was the same when basic fibroblast growth factor was used alone or when it was combined with sulfated polysaccharides. Acidic fibroblast growth factor totally reversed the effects of sulfated polysaccharides on the repair process by enhancing endothelial cell proliferation and allowing endothelial cell migration.
Bsp 12861 restriction fragment length polymorphism detects Ag(c/g) locus of human apolipoprotein B in all 17 persons studied.
Authors: Ma Y H , Wang X B , Bütler R , Schumaker V N
Published: June 2011

Southern blot analysis of the genomic DNA from 17 individuals showed perfect correspondence between a Bsp 12861 restriction fragment length polymorphism (RFLP) and the Ag(c/g) locus on human apolipoprotein (apo) B. The RFLP polymorphism is caused by a C--------T transition at nucleotide 421 on the cDNA, resulting in a threonine-to-isoleucine conversion. Thus, three of the five Ag sites have now been tentatively located on the 4536 residue apo B peptide at amino acyl residues 71: Ag(c/g), 591 (Ag(a1/d), and 4154 Ag(t/z).
Use of 3H-cholesteryl linoleyl ether as a quantitative marker for loss of cholesteryl ester during regression of cholesterol-induced aortic atheromas in rabbits.
Authors: Stein O , Hollander G , Dabach Y , Halperin G , Stein Y
Published: June 2011

In this study, use was made of 3H-cholesteryl linoleyl ether (3H-CLE) to follow regression of aortic atheromatosis induced by feeding cholesterol to rabbits. After a 3-month induction period, the rabbits were divided into two groups with an attempt to match them by plasma cholesterol levels. They were injected with rabbit plasma labeled with 3H-CLE, and the baseline group rabbits were killed 10 to 12 days after injection. The experimental (regression) group rabbits were given rabbit chow containing 3% cholestyramine and were killed up to 330 days thereafter. Aortic 3H-CLE of both the baseline and the regression groups correlated highly with the plasma cholesterol levels at the time of injection of label. The radioactivity recovered in the aortas of the baseline and regression groups was not significantly different, indicating retention of label between day 12 and 330 days after injection. During that time, the mean aortic cholesteryl ester content decreased from 7.6 +/- 1.3 mg to 3.1 +/- 0.7 mg (p less than 0.01). The specific activity of 3H-CLE/cholesteryl ester determined in the aortic arch and the thoracic and abdominal aorta was significantly increased in all three regions examined in the regression group as compared to the baseline group. The present data show that 3H-CLE is retained in the atheromatous aorta for at least 330 days and that its use may add another dimension to the quantitative evaluation of regression of atherosclerotic lesions.
Contraceptive steroid effects on lipids and lipoproteins in cynomolgus monkeys.
Authors: Parks J S , Pelkey S J , Babiak J , Clarkson T B
Published: June 2011

Seventy-three adult female cynomolgus monkeys fed an atherogenic diet were studied to determine the effect of two different combination contraceptive steroid preparations containing equivalent amounts of estrogen but different progestin components on plasma lipids and lipoproteins. Our hypothesis was that any high density lipoprotein (HDL) lowering effect of the contraceptive steroid preparations was proportional to the rise in total serum cholesterol caused by the progestins. For 2 years, one group (Ovral [Wyeth Laboratories], n = 23) received 75 micrograms norgestrel and 7.5 micrograms ethinyl estradiol daily, while another (Demulen [Searle & Co.], n = 25) received 150 micrograms ethynodiol diacetate and 7.5 micrograms ethinyl estradiol daily. The control group (n = 24) received no treatment. On average, the two oral contraceptive groups had higher total serum cholesterol and triglyceride concentrations but lower HDL cholesterol concentrations and smaller low density lipoproteins (LDL) compared with the control group. There was an inverse relationship between total serum cholesterol and HDL cholesterol for all three groups, but at any given total serum cholesterol concentration between 350 and 500 mg/dl, the Ovral group had HDL cholesterol concentrations that averaged 37% and 14% lower than the control and Demulen groups, respectively. The decrease in HDL concentrations with oral contraceptive treatment was associated with a sharp decrease in (HDL2b)gge protein (82% for Ovral and 59% for Demulen) and a corresponding increase in (HDL3b,c)gge protein as determined by gradient gel electrophoresis. Of 23 animals in the Ovral group, six had HDL subfractions greater than 10 nm diameter (HDL2b)gge compared with 22 of 24 animals in the control group. Although LDL size, on average, was smaller and plasma triglycerides were greater with oral contraceptive treatment compared with controls, there was no apparent relationship between LDL size and plasma triglyceride concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
In vivo modulation of endothelial F-actin microfilaments by experimental alterations in shear stress.
Authors: Kim D W , Gotlieb A I , Langille B L
Published: June 2011

F-actin microfilament reorganization in response to alterations in shear stress has not been experimentally tested in vivo. In the current study, we analyzed changes in F-actin distribution in endothelial cells around the site of a coarctation performed in the midabdominal aorta of rabbits. The coarctation caused a 60% decrease in luminal diameter and produced three distinct zones: 1) a high shear region immediately upstream of the coarct (Zone I); 2) a region of low, fluctuating shear immediately downstream of the coarct (Zone II); and 3) an annular vortex characterized by high shear extending 0.5 to 3 mm downstream of the coarct (Zone III). Endothelial cells of control abdominal aortas were ellipsoid in shape and aligned in the direction of blood flow. They displayed a prominent circumferential band of microfilaments and short, thin stress fibers. Near coarctations, cells of Zone I were much more elongate, and stress fibers were markedly thicker and longer than in control abdominal aortas. In Zone II, cells were polygonal in shape and showed a prominent peripheral band of microfilaments and central stress fibers. Zone III cells were similar in shape to control abdominal aortic endothelial cells but showed very striking central stress fibers. These findings indicate that in vivo F-actin microfilament distribution can be modulated by experimentally altering flow conditions. F-actin redistribution in response to elevated shear stresses may increase cell-substrate adhesion and thus maintain endothelial integrity.
Insulin, body mass index, and cardiovascular risk factors in premenopausal women.
Authors: Wing R R , Bunker C H , Kuller L H , Matthews K A
Published: June 2011

This study assessed the relationship between insulin, glucose, body mass index, and cardiovascular risk factors in a sample of 489 white premenopausal women. All women were participants in the Healthy Women Study (University of Pittsburgh) and had normal blood pressure and fasting blood glucose of less than 140 mg/dl and a 2-hour value after a 75-g glucose load of less than 200 mg/dl. Both body mass index and fasting insulin were significantly and independently associated with blood pressure, triglycerides, and high density lipoprotein (HDL) cholesterol and its subfractions. Body mass index and fasting insulin were more strongly associated with coronary heart disease (CHD) risk factors than were 2-hour insulin, or fasting or 2-hour glucose; glucose levels did not contribute independently to multivariate predictions of any of the CHD risk factors. When patients were divided into tertiles according to fasting insulin and body mass index, there were significant main effects of insulin and body mass index on blood pressure, triglycerides, and HDL cholesterol and its subfractions; the interaction of insulin times body mass index was also significant for systolic blood pressure, triglycerides, and apoprotein B. These data confirm the previous findings of a strong association between insulin and CHD risk factors and extend this to healthy premenopausal women.
Relation of cholesterol to apolipoprotein B in low density lipoproteins of children. The Bogalusa Heart Study.
Authors: Srinivasan S R , Wattigney W , Webber L S , Berenson G S
Published: June 2011

Cholesterol and apolipoprotein (apo) B contents and their relationship within serum low density lipoprotein (LDL) were examined in 2018 children, ages 8 to 17 years, from a biracial community. The levels of LDL cholesterol and LDL apo B showed significant race-related differences (blacks greater than whites) in both boys and girls and gender-related differences (girls greater than boys) in white children. These LDL measures associated inversely and significantly with both age and Tanner stage, more so in boys than in girls. The black-white differences in LDL measures persisted after adjusting for the covariates (sexual maturation, age, adiposity, oral contraceptive use, cigarette smoking, and alcohol use). The distribution of LDL cholesterol for a given range of LDL apo B varied considerably, despite a strong correlation (r = 0.91) between these variables, indicating that measuring LDL cholesterol alone does not accurately reflect LDL concentration. The ratio of cholesterol to apo B in LDL ranged from 1.01 (5th percentile) to 1.42 (95th percentile) among the four race-gender groups, suggesting marked interindividual variation in composition. That this ratio was significantly elevated in black children indicates the occurrence of relatively larger, less dense, and cholesterol-enriched LDL particles in blacks. Significant independent associations were noted between LDL cholesterol/apo B ratios and the levels of serum total cholesterol (positive) and triglycerides (negative), suggesting the influence of pool size of different lipoproteins on LDL composition. These observations may help identify a subgroup of children with apo B-enriched LDL particles who are potentially at risk for coronary artery disease.
Effect of heparin on adaptation of vein grafts to arterial circulation.
Authors: Kohler T R , Kirkman T , Clowes A W
Published: June 2011

We studied the effect of heparin on wall thickening in balloon-injured carotid arteries and vein grafts in rabbits. Heparin (0.3 mg/kg of body weight/hour) reduced intimal cross-sectional area in balloon-injured carotid arteries at 2 weeks (0.20 +/- 0.05 mm2 vs. 0.05 +/- 0.02 mm2, p = 0.02). Autoradiography after a single pulse of tritiated thymidine revealed no labeling in the few intimal cells present in heparin-treated animals, whereas control smooth muscle cells (SMC) had a 10% labeling index. Heparin did not affect medial proliferation, suggesting that the decrease in intimal thickening was largely due to inhibition of SMC migration into the intima. Heparin caused a slight reduction in intimal cross-sectional area at 2 weeks in vein grafts (0.17 +/- 0.03 mm2 vs. 0.09 +/- 0.02 mm2, p = 0.03) but no significant reduction in wall thickness at any other time and no reduction in SMC proliferation rate (thymidine labeling index). DNA content per surface area or dry weight was the same in control and heparin-treated vein grafts at 4 weeks, implying that SMC content and the amount of matrix made by individual SMC was not affected. These data suggest that either SMC in veins are less susceptible to heparin than SMC in arteries, or the mechanism of thickening is substantially different. Heparin may not block all forms of SMC proliferation and may only be a weak inhibitor in processes that primarily are in response to changes in pressure.
Serum lipids and lipoproteins as predictors of atherosclerosis. An autopsy study.
Authors: Reed D M , Strong J P , Resch J , Hayashi T
Published: June 2011

A prospective study of autopsy-determined measures of atherosclerosis in aortas and coronary and cerebral arteries was completed for a group of 83 men who were free of clinical cardiovascular disease and cancer when they entered the Cooperative Lipoprotein Phenotyping Study in 1970. Total cholesterol minus high density lipoprotein cholesterol (HDL-C) was significantly associated with measures of atherosclerosis in all three groups of vessels. The patterns of associations for total, low density lipoprotein, and very low density lipoprotein cholesterol were similar but generally weaker and not significant for atherosclerosis in the cerebral arteries. Inverse associations of HDL-C with atherosclerosis in the circle of Willis and aorta were significant, but those for the coronary arteries were not. These associations were independent of other major risk factors for atherosclerosis in multivariate analyses. Similarities between these findings and those for clinical cardiovascular disease in the same cohort indicate that the opposing patterns of increased risk of clinical cardiovascular disease associated with total cholesterol and the decreased risk associated with HDL-C also exists at the level of atherosclerosis in a variety of arteries.
Quantitation and localization of apolipoproteins [a] and B in coronary artery bypass vein grafts resected at re-operation.
Authors: Cushing G L , Gaubatz J W , Nava M L , Burdick B J , Bocan T M , Guyton J R , Weilbaecher D , DeBakey M E , Lawrie G M , Morrisett J D
Published: June 2011

Lp[a] is a lipoprotein whose plasma concentration is highly correlated with cardiovascular disease. Its protein moiety, apoLp[a], consists of two large polypeptides, apo[a] and apo B. The possible contribution of Lp[a] to atherosclerosis in saphenous vein aortocoronary bypass grafts was studied in a population of patients undergoing coronary re-bypass surgery. The vein graft tissue levels of apoLp[a] were compared with graft duration, gross and light microscopic pathology, as well as plasma levels of apoLp[a]. The localization pattern of apo[a] and apo B in vein graft tissue was determined. In addition, the plasma levels of cholesterol, triglycerides, apoproteins (apo) A-I, A-II, and E were measured. In a representative subpopulation of 17 patients with a mean age of 63 years from whom grafts with a mean duration of 112 months were resected, the mean total plasma cholesterol level was 221 mg/dl, the mean high density lipoprotein cholesterol level was 31 mg/dl, and the mean plasma triglyceride level was 228 mg/dl. In normal saphenous veins, the level of apoLp[a] was below measurable limits (less than 2 ng/mg), and the level of apo B was very low (3.3 ng/mg). In resected grafts, the mean tissue level of apoLp[a] was 32 ng/mg, and that of apo B was 70 ng/mg, demonstrating the net accumulation of these apoproteins in veins from the time of their grafting into the arterial bed. The apoLp[a]/apo B ratio was determined in 77 tissue segments from 59 grafts (28 patients) and was found to be 0.313. This tissue ratio was significantly higher (p = 0.02) than the plasma apoLp[a]/apo B ratio from these patients, which was 0.132. Immunostaining showed co-localization of apo[a] and apo B in the neointima of grafts. The most abundant pathologic features observed in resected grafts were proliferated intima (43/52), thrombus (28/52), and atherosclerotic core regions (21/52). The level of tissue apo B correlated well with the abundance of core regions (r = 0.501), whereas the level of tissue apoLp[a] did not correlate as well with this feature (r = 0.233). Although apo[a] and apo B are almost absent from normal saphenous vein, these apoproteins (and presumably the lipoproteins Lp[a] and low density lipoprotein) accumulate in bypass vein grafts. The data support the view that these lipoproteins play a significant role in vein graft atherosclerosis.
Beta-VLDL metabolism by pigeon macrophages. Evidence for two binding sites with different potentials promoting cholesterol accumulation.
Authors: Adelman S J , St Clair R W
Published: June 2011

Previous studies from our laboratory (J Lipid Res 1988;29:643-656) have shown that thioglycolate-elicited peritoneal macrophages from White Carneau and Show Racer pigeons, like mammalian macrophages, have on their surfaces specific receptors for acetylated low density lipoprotein (acLDL) and beta-migrating very low density lipoproteins (beta-VLDL). The binding kinetics of beta-VLDL were complex, however, suggesting more than one binding site. The purpose of the present study was to further characterize these beta-VLDL binding sites. Scatchard analysis of 125I-beta-VLDL binding curves indicated at least two classes of binding sites. The first binds pigeon beta-VLDL and LDL with high affinity (Kd approximately 7 micrograms/ml), is down-regulated by cholesterol loading, requires calcium, and is destroyed by the proteolytic enzyme, pronase. This pigeon beta-VLDL receptor is specific for pigeon beta-VLDL and LDL and does not recognize HDL, acLDL, methyl LDL, cynomolgus monkey LDL, or rabbit beta-VLDL. Like the mammalian macrophage beta-VLDL receptor, the "pigeon beta-VLDL receptor" has many of the characteristics of an LDL receptor. The second class of binding sites is relatively nonspecific, recognizing both pigeon and rabbit beta-VLDL, LDL, acLDL, methyl LDL, and HDL. Binding to this site is not altered by incubation of macrophages with pronase or by cholesterol loading. This binding site has low affinity for beta-VLDL (Kd approximately 100 micrograms/ml), but high capacity. We have called this the "lipoprotein binding site," a term used by others to describe similar lipoprotein binding characteristics on a variety of cells. Not only does binding to this site promote the internalization and degradation of lipoproteins, but it may also facilitate the independent uptake of cholesterol. This conclusion is based on the observation that more cholesterol accumulates in cells incubated with rabbit beta-VLDL, which binds only to the lipoprotein binding site, than can be accounted for by beta-VLDL uptake and degradation. Since the lipoprotein binding site recognizes a variety of normal, as well as abnormal, lipoproteins, it would not require the generation of abnormal lipoprotein products, as must occur with the scavenger receptor, to promote the accumulation of cholesteryl esters in macrophages of atherosclerotic lesions. This, coupled with the fact that the lipoprotein binding site is not down-regulated by cholesterol loading, suggests that it could provide an alternative mechanism to the scavenger receptor pathway for the formation of foam cells.
Effect of naloxone, a specific opioid inhibitor, on blood pressure fall during sleep.
Authors: Rubin P , Blaschke T F , Guilleminault C
Published: June 2011

The study was designed to investigate the possible role of endogenous opioids in the fall in blood pressure (BP) seen during initial sleep. Seven normal men, ages 20-30 years, were studied for three consecutive nights. Each night, electroencephalogram, chin electromyogram, electrooculogram, heart rate (all continuously), and blood pressure (every 15 minutes) were recorded. Night 1 was used for orientation. On nights 2 and 3, subjects received, in randomized order, an infusion of naloxone 0.2 mg/kg over 1 minute or volume-matched saline. Blood pressure data from the first 4 hours of non-rapid eye movement sleep were combined. On the placebo night, systolic BP fell from 114.6 +/- 6 mm Hg to 103.7 +/- 8 mm Hg (+/- SD) (p < 0.05, Wilcoxon rank-sum test). On the naloxone night, systolic BP did not change. Neither diastolic BP nor heart rate were influenced by naloxone. these data suggest that endogenous opioids could be involved in the fall in systolic BP seen during initial sleep.
Echocardiographic assessment of right bundle branch injury after repair of tetralogy of Fallot.
Authors: Pickoff A S , Mehta A V , Casta A , Ferrer P L , Wolff G S , Tamer D F , Garcia O L , Gelband H
Published: June 2011

Nineteen patients, ages 3 1/2-18 years, with electrocardiographic evidence of right bundle branch injury after intracardiac repair of tetralogy of Fallot, underwent invasive intracardiac electrophysiologic evaluation 1-13 years (mean 4.4 years) postoperatively. Categorization of the site of right bundle branch injury as proximal or distal was made by determining the V-RVA interval. In 11 of the patients, the V RVA interval was prolonged (> 35 msec), indicating proximal right bundle branch injury and in the other eight it was normal (< 35 msec), indicating distal bundle branch injury. Within 24 hours of the study, all patients were studied by M-mode echocardiography. Measurements were made of the tricuspid valve closure, mitral valve closure and the difference between the two, or the delta value. All but one patient with distal bundle branch injury had delta values of less than 40 msec (range 8-38 msec), while 10 or 11 patients with proximal bundle branch injury had delta values greater than 40 msec (range 41-116 msec). there was a significant positive correlation (r = 0.74, p < 0.001) between V-RVA and the delta value. We conclude that the delta value is an indicator of relative activation delay of the right ventricle, and therefore, in most cases, proximal vs distal bundle branch injury can be diagnosed noninvasively.
Systolic time intervals in adolescents. Normal standards for clinical use and comparison with children and adults.
Authors: Wanderman K L , Hayek Z , Ovsyshcher I , Loutaty G , Cantor A , Gussarsky Y , Gueron M
Published: June 2011

Systolic time intervals were measured in 147 healthy 13-19-year-old adolescents to derive regression equations for clinical use in this age group and to determine to what extent they differ from those of children and adults. Stepwise regression analysis showed that heart rate was the only variable consistently and significantly related to electromechanical systole (QS2), left ventricular ejection time (LVET) and preejection period (PEP). None of the other variables tested (age, height, weight, body surface area, blood pressure, hemoglobin, hematocrit and serum electrolytes), when used alone, were relevant variables in relation to QS2, LVET or PEP. The PEP/LVET ratio in adolescents was essentially independent of heart rate, as in children and adults. The regression lines for QS2, LVET and PEP in adolescents fall between those for children and adults, indicating that there is a distinct tendency toward lengthening of all the systolic time intervals with age, independent of changes in heart rate. The PEP lengthens proportionately more than the LVET, resulting in a progressive increase in the mean PEP/LVET ratio from childhood (0.30) to adolescence (0.32) and to adulthood (0.345). The precise hemodynamic factors underlying these changes with increasing age remain to be determined.
ST-segment elevation with elective DC cardioversion.
Authors: Chun P K , Davia J E , Donohue D J
Published: June 2011

Elective direct-current cardioversion was performed in three patients with atrial fibrillation. Transient ST-segment elevation on monitored leads, lasting seconds, was recorded after cardioversion in all three patients. LDH, CPK isoenzymes, and myocardial scintigraphy did not reveal myocardial damage. Elective cardioversion should be performed with caution, for the potential for cardiac damage cannot be ignored.
Electrophysiologic delineation of the intraventricular His bundle in two patients with endocardial cushion type of ventricular septal defect.
Authors: Dick M , Behrendt D M , Jochim K E , Castaneda A R
Published: June 2011

Two patients who had an endocardial cushion type of ventricular septal defect underwent electrophysiologic studies for detection of specialized conduction tissue during operative repair. In one patient, with an inferior leftward frontal plane QRS axis on the ECG, we recorded an intraventricular His bundle electrograms from both the anterosuperior and posteroinferior margins of the defect, suggesting dual atrioventricular conduction tracts (branching intraventricular His bundle). These anatomic and electrophysiologic findings may account for the more normally oriented QRS frontal plane axis on the surface ECG of both of these patients and support the hypothesis that the changes observed on the ECGs of patients with the various forms of endocardial cushion defect can be explained by alterations in the anatomic configuration of the specialized atrioventricular conduction tissue.
Significance of exercise-induced ST-segment elevation in patients without myocardial infarction.
Authors: Specchia G , de Servi S , Falcone C , Angoli L , Mussini A , Bramucci E , Marioni G P , Ardissino D , Salerno J , Bobba P
Published: June 2011

Sixteen patients with exercise-induced ST-segment elevation and without a history of myocardial infarction or left ventricular aneurysm were studied. Fourteen complained of angina at rest, which was associated with ST-segment elevation in the same leads where it was recorded during exercise, and two patients had only exertional angina. Exercise-induced ST-segment elevation was generally reproducible in subsequent exercise tests performed in different hours of the day, but exercise tests repeated a mean of 15 months later did not induce this electrocardiographic abnormality. All patients had a marked susceptibility to coronary spasm, as shown by the response to the ergonovine test (12 positive tests in 12 patients) and by the occurrence of spontaneous spasm during coronary arteriography in two patients. In addition, coronary arteriography, performed in seven patients at the time of exercise-induced ST-segment elevation, revealed spasm of a major coronary vessel in all. In two patients we documented that exercise-induced ST-segment elevation was accompanied by a decreased coronary blood flow and increased coronary vascular resistance. We conclude that exercise-induced ST-segment elevation in patients without a history of myocardial infarction or left ventricular aneurysm is caused by coronary spasm of a major coronary vessel.