bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diminished vascular response to inhibition of endothelium-derived nitric oxide and enhanced vasoconstriction to exogenously administered endothelin-1 in clinically healthy smokers.
Authors: Kiowski W , Linder L , Stoschitzky K , Pfisterer M , Burckhardt D , Burkart F , Bühler F R 
Published: June 2012

BACKGROUND
Smoking is a major risk factor for the development of atherosclerosis. Because endothelial dysfunction may be a marker for future atherosclerosis, we investigated the effects of smoking on endothelium-dependent control of vascular tone.

METHODS AND RESULTS
The effects of brachial arterial infusions of NG-monomethyl-L-arginine (L-NMMA), a nitric oxide synthesis inhibitor; sodium nitroprusside; endothelin-1; and norepinephrine on forearm blood flow (strain-gauge plethysmography) were compared in 29 long-term smokers and 16 nonsmokers. The acute effects of smoking on systemic hemodynamics, plasma catecholamines, and forearm vascular responses to these compounds were investigated in smokers only. Smokers did not differ from nonsmokers (n = 16) regarding the vascular effects of sodium nitroprusside (n = 13) or vasoconstriction due to norepinephrine and endothelin-1 (n = 16). Low-dose endothelin-1-induced vasodilation, believed to reflect endothelial prostacyclin or nitric oxide release, was absent in smokers (n = 16), and their increase of forearm vascular resistance (FVR) after L-NMMA (n = 13) was impaired (35.6 +/- 27.9% versus 118.8 +/- 43.2%, P < .001). Short-term smoking (n = 11) increased blood pressure, heart rate, and plasma epinephrine concentrations (P < .05 or less); enhanced endothelin-1-induced vasoconstriction (delta FVR, 457 +/- 192% versus 254 +/- 143%, P < .01); and decreased norepinephrine-induced vasoconstriction (P < .05), but had no effect on the other interventions.

CONCLUSIONS
Long-term smoking is associated with a diminished nitric oxide-dependent component of basal vascular tone and an impaired endothelium-dependent vasodilator response to low-dose endothelin-1 and short-term smoking enhances endothelin-1-induced vasoconstriction. Impaired endothelial control of vascular tone might reflect impairment of normal antiatherosclerotic endothelial functions in smokers, but the relevance of smoking-induced enhancement of endothelin-1 vasoconstriction remains to be determined.
Mechanism of efficacy of 2-amino oleic acid for inhibition of calcification of glutaraldehyde-pretreated porcine bioprosthetic heart valves.
Authors: Chen W , Schoen F J , Levy R J 
Published: June 2012

BACKGROUND
Calcification is a frequent cause of the clinical failures of glutaraldehyde-pretreated bioprosthetic heart valves (BPHV) fabricated from glutaraldehyde-cross-linked porcine aortic valves. 2-Amino oleic acid (AOA) has been shown in previous in vivo studies to be a promising anticalcification agent. Our objective was to investigate the mechanism of calcification inhibition mediated by AOA pretreatment of porcine aortic valve bioprostheses.

METHODS AND RESULTS
BPHV tissues were treated with an AOA solution for 72 hours before experimentation. The diffusion of AOA across both cusp and aortic wall was evaluated. The lag time for AOA to diffuse across the aortic wall was prolonged compared with that of the cusp. An extraction study was performed to determine the stability of AOA binding; the results indicated that the binding was relatively stable regardless of solvent extraction conditions. The interaction between ionic calcium and AOA on treated tissue also was investigated by evaluating the patterns of calcium diffusion across both treated and untreated tissues. The results showed that AOA significantly reduced the diffusion of calcium. AOA inhibition of aortic valve calcification (calcium level, 5.5 +/- 3.0 mg/g of tissue compared with control; calcium level, 91.2 +/- 19.5 mg/g of tissue) but not aortic wall (calcium level, 158.7 +/- 10.3 mg/g of tissue compared with control; calcium level, 157.5 +/- 7.9 mg/g of tissue) was demonstrated on representative specimens from valves implanted in left ventricular apicoaortic shunts explanted after 150 days.

CONCLUSIONS
AOA covalently binds to glutaraldehyde-pretreated bioprosthetic heart valve tissue, presumably as the result of an aldehyde-amino reaction. Covalently bound AOA diminishes Ca2+ diffusion compared with non-AOA-pretreated bioprosthetic tissues. This may explain in part the anticalcification mechanism of AOA. Furthermore, AOA inhibits calcification of porcine BPHV cusps in the circulation.
Acute and follow-up intravascular ultrasound findings after balloon dilation of coarctation of the aorta.
Authors: Sohn S , Rothman A , Shiota T , Luk G , Tong A , Swensson R E , Sahn D J 
Published: June 2012

BACKGROUND
The study objective was to examine the vascular wall changes caused by balloon dilation of coarctation of the aorta (CoA) acutely and at short-term follow-up using intravascular ultrasound imaging. Intravascular ultrasound has been valuable in assessing the vessel wall changes in coronary and peripheral arteries after balloon dilation, often with more detail than angiography.

METHODS AND RESULTS
Intravascular ultrasound imaging, using 4.8F, 20-MHz or 6.2F, 12.5-MHz catheters on either Diasonics or HP scanners, was performed in 17 patients during balloon angioplasty for native (n = 12) and recurrent (n = 5) CoAs. Nine patients were also studied at the time of follow-up cardiac catheterization 28.1 +/- 18.0 months after angioplasty. Immediately after dilation, the mean pressure gradient across the CoA decreased from 42.9 +/- 16.4 to 9.0 +/- 5.4 mm Hg (P < .001) and the mean diameter of the coarcted segment increased from 4.4 +/- 1.9 to 7.9 +/- 2.4 mm (P < .001). An intimal tear or flap was noted by ultrasound in 12 of the 12 native CoAs and 4 of the 5 recoarctations. In contrast, only 6 of the native CoAs and 2 of the recoarctations had an intimal flap or dissection detected by angiography. At follow-up, the residual pressure gradient did not significantly change from that measured immediately after dilation, but the CoA diameter increased from 7.8 +/- 1.5 to 9.9 +/- 2.3 mm (P < .01). No aneurysms were detected. Four of the 9 patients showed ultrasonic and angiographic evidence of healing and remodeling with diminution in size or disappearance of the intimal tears.

CONCLUSIONS
There is a high incidence of intimal tears and dissections immediately after balloon angioplasty for native and recurrent CoAs. Intravascular ultrasound is more sensitive than angiography in detecting the vascular wall changes. Even significant intimal tears are not necessarily associated with aneurysm formation, and many decrease in size or disappear at short-term follow-up.
Selective loss of microvascular endothelial function in human hypercholesterolemia.
Authors: Gilligan D M , Guetta V , Panza J A , García C E , Quyyumi A A , Cannon R O 
Published: June 2012

BACKGROUND
Endothelial dysfunction is increasingly recognized as an early and important feature of vascular disease. Endothelium-dependent vasodilation is impaired in humans with hypercholesterolemia, although it is unknown whether this defect is selective for some pathways of nitric oxide production or indicates a more generalized abnormality of endothelial function. The aim of this study was to further elucidate the nature of endothelial dysfunction in human hypercholesterolemia by comparing vascular responses of agonists that use different signal transduction pathways to activate production of nitric oxide.

METHODS AND RESULTS
Forearm flow was measured in 12 hypercholesterolemic patients (total cholesterol, 286 +/- 35 mg/dL [mean +/- SD]) aged 50 +/- 11 years and in 12 healthy subjects (total cholesterol, 173 +/- 27 mg/dL) aged 48 +/- 7 years using strain-gauge plethysmography and brachial artery drug infusions. The endothelium-dependent vasodilators used were acetylcholine (7.5, 15, and 30 micrograms/min), which uses a pertussis toxin-sensitive signal transduction pathway, and bradykinin (100, 200, and 400 ng/min), which uses a pertussis toxin-insensitive signal transduction pathway to activate nitric oxide production. Sodium nitroprusside (0.8, 1.6, and 3.2 micrograms/min) was used to test endothelium-independent vasodilation. The maximum flow in response to acetylcholine was markedly impaired in patients compared with healthy subjects (8.0 +/- 5.1 versus 17.5 +/- 7.7 mL.min-1. 100 mL-1, P = .002). However, the maximum forearm flow in response to bradykinin was similar in the two groups (13.0 +/- 4.5 versus 16.2 +/- 5.5 mL.min-1 x 100 mL-, P = .14), as was the maximum flow in response to sodium nitroprusside (7.0 +/- 2.8 versus 8.4 +/- 2.2 mL.min-1 x 100 mL-1, P = .13). NG-Monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, reduced the maximum forearm vasodilation induced by bradykinin to the same extent in patients and in healthy subjects (-29 +/- 8% versus -32 +/- 6% reduction in peak flow, P = .80), with similar maximum flows in response to bradykinin (9.2 +/- 4.0 versus 10.4 +/- 2.6 mL.min-1 x 100 mL-1, P = .35).

CONCLUSIONS
Hypercholesterolemic patients are capable of normal nitric oxide bioavailability in response to bradykinin. Impairment of microvascular endothelial vasodilator function in human hypercholesterolemia is selective, and the defect occurs at the level of the acetylcholine receptor or its signal transduction pathway.
Utrophin localization in normal and dystrophin-deficient heart.
Authors: Pons F , Robert A , Fabbrizio E , Hugon G , Califano J C , Fehrentz J A , Martinez J , Mornet D 
Published: June 2012

BACKGROUND
The localization of dystrophin at the sarcolemma of cardiac skeletal fibers and cardiac Purkinje fibers has been described. Dystrophin deficiency produces clinical manifestations of disease in skeletal muscles and hearts of patients with Duchenne and Becker muscular dystrophy. Utrophin (or dystrophin-related protein), a dystrophin homologous protein, was found to be expressed in fetal muscles and reexpressed in dystrophin-deficient skeletal muscle fibers. We therefore examined utrophin expression in normal and in dystrophin-deficient hearts.

METHODS AND RESULTS
The expression and subcellular distribution of utrophin was examined in cardiac muscle by immunoblot and immunofluorescence analysis in normal bovine heart compared with dystrophin. Utrophin expression was also examined in normal and dystrophin-deficient hearts of MDX mice. Three monoclonal antibodies reacting with dystrophin and utrophin solely or reacting with both proteins along with two polyclonal antibodies reacting with either utrophin or dystrophin and utrophin were tested. In normal bovine heart, utrophin was not expressed at the periphery of fibers but was strongly expressed in intercalated disks and in the cytoplasm of cardiac Purkinje fibers. In cardiocytes, utrophin was colocalized along transverse T tubules with dystrophin. Dystrophin was present at the periphery of cardiocytes and cardiac Purkinje fibers as well as in transverse T tubules but was absent or faintly expressed in intercalated disks. The results with monoclonal and polyclonal antibodies were identical. Western blot analysis revealed that the detected molecules corresponded only to a 400-kD protein band and not to possible shorter transcripts of utrophin or dystrophin (apo-utrophin or apo-dystrophin). In dystrophin-deficient hearts of MDX mice, utrophin alone was abundant but not organized in the same networklike distribution.

CONCLUSIONS
This first localization of utrophin in normal heart (in Purkinje fibers, transverse tubules, and intercalated disks) showed a distinct subcellular localization of this protein with dystrophin, suggesting an important function of this protein in intercellular communication. In dystrophin-deficient hearts of MDX mice, utrophin alone is overexpressed as in skeletal muscle sarcolemma, an area normally occupied by dystrophin but not organized in the same networklike distribution.
Heart disease, cancer, and stroke mortality trends and their interrelations. An international perspective.
Authors: Thom T J , Epstein F H 
Published: June 2012

BACKGROUND
Changes in mortality from heart disease, cancer, and stroke over recent decades in many countries have received much attention. However, comprehensive and concurrent analyses of these trends and their effect on total mortality have been lacking. Moreover, the extent to which the trends for one disease may relate to those for another disease is unknown. Concordance of trends for major diseases would suggest that they have common causes and thus may be responsive to the same preventive measures.

METHODS AND RESULTS
Age-adjusted death rates for total mortality and mortality from heart disease, stroke, lung cancer, and cancer other than lung cancer were obtained for the years 1950 to 1987 in 27 countries by sex and ages 35 to 74 years from the World Health Organization statistical reports. Concordance of mortality trends was assessed for ages 35 to 74 between 1950 and 1983 through visual inspection and semiquantitative measurements of percentage change over time. The epidemic increase in heart disease mortality ended in the 1960s or 1970s in most industrialized countries; death rates often declined very steeply. Stroke mortality also changed from an increase to a decline or from a modest to a steep decline in the 1960s or 1970s. Lung cancer mortality slopes generally changed from a steep increase to either a modest increase, a flat trend, or a decline; the changes in slope are lagging behind those for heart disease and stroke. These improvements influenced trends for total mortality. Cancer other than lung cancer trends are less distinct than those for the three other causes of mortality. Yet, testing them for concordance with heart disease trends reveals that they are mostly concordant on a time-lag analysis that assumes that heart disease responds more rapidly to a change in lifestyle or environment than cancer. Trends for heart disease and lung cancer in men also tend to be concordant on time-lag analysis. Heart disease and stroke trends have become more concordant with time.

CONCLUSIONS
Trends for mortality from heart disease, stroke, lung cancer, and, less distinctly, cancer other than lung cancer, tend to be similar in different countries, leading to a corresponding similarity in total mortality trends. An analysis of trends for pairs of diseases within countries indicates a tendency toward concordance of trends, suggesting the existence of common causes amenable to the same preventive measures. This analysis of international mortality trends is intended to stimulate further research along these lines, as a guide to preventive and therapeutic action.
Localized arterial wall drug delivery from a polymer-coated removable metallic stent. Kinetics, distribution, and bioactivity of forskolin.
Authors: Lambert T L , Dev V , Rechavia E , Forrester J S , Litvack F , Eigler N L 
Published: June 2012

BACKGROUND
Coronary stenting is associated with two major complications: subacute thrombosis and neointimal proliferation resulting in restenosis. Our hypothesis is that the biocompatibility of metallic stents can be improved by coating with a polymer membrane that delivers agents that favorably modify the local arterial microenvironment. This study evaluates the kinetics, distribution, and bioactivity of the model drug forskolin delivered to the local arterial wall by a polyurethane-coated removable metallic stent.

METHODS AND RESULTS
Stents were used in rabbit carotid arteries (n = 20) for as long as 24 hours. The quantity of forskolin bound to the stent decreased exponentially with a half-life of 5.8 hours. Blood concentrations peaked at 140 +/- 39 pg/microL at 4 hours. The adjacent arterial media contained 60 +/- 39 ng/mg, which was 380- and 460-fold greater than the contralateral carotid media and the systemic blood, respectively (P < .0001). Media forskolin concentrations declined exponentially over time with a tissue half-life of 5.0 hours. Drug distributed throughout the vessel wall with decreasing gradients in the radial and axial dimensions consistent with a diffusion process. Removal of the stent was associated with a 100-fold decline in media forskolin concentration within 2 hours. Forskolin release was associated with a sustained 92% increase in carotid blood flow and a 60% decrease in local arterial resistance compared with coated control stents (P < .005). In another set of rabbits (n = 14) using a carotid crush injury, flow-reduction model, forskolin prolonged the time to flow variation and occlusion by 12-fold compared with the use of bare metal stents and 5-fold compared with the use of polyurethane-coated stents (P < .0001).

CONCLUSIONS
A polymer-coated metallic stent can deliver forskolin to the local arterial wall in high concentrations relative to the blood or other tissues. High local drug concentrations are dependent on maintaining stent-to-tissue gradients. The delivered drug is biologically active, demonstrating vasodilating and antiplatelet properties.
Ca(2+)-transporting ATPase, phospholamban, and calsequestrin levels in nonfailing and failing human myocardium.
Authors: Movsesian M A , Karimi M , Green K , Jones L R 
Published: June 2012

BACKGROUND
Observations of abnormalities in the diastolic components of intracellular Ca2+ transients in failing human left ventricular myocardium have raised the possibility that reductions in the level or function of sarcoplasmic reticulum proteins involved in Ca2+ transport contribute to the pathophysiology of dilated cardiomyopathy in humans. Functional assays, however, have revealed no differences in ATP-dependent Ca2+ transport or its modulation by phospholamban in sarcoplasmic reticulum-enriched microsomes prepared from nonfailing and failing human left ventricular myocardium. The purpose of the present study was to quantify protein levels of Ca(2+)-transporting ATPase, phospholamban, and calsequestrin directly in nonfailing and failing human left ventricular myocardium.

METHOD AND RESULTS
Total protein extracts were prepared from nonfailing left ventricular myocardium from the hearts of unmatched organ donors with normal left ventricular contractility (n = 6) and from failing left ventricular myocardium from the excised hearts of transplant recipients with class IV heart failure resulting from idiopathic dilated cardiomyopathy (n = 6). Ca(2+)-transporting ATPase, phospholamban, and calsequestrin contents were determined by quantitative immunoblotting with monoclonal and affinity-purified polyclonal antibodies. The levels of the three proteins were identical in nonfailing and failing human left ventricular myocardium.

CONCLUSIONS
These results indicate that protein levels of Ca(2+)-transporting ATPase, phospholamban, and calsequestrin are not diminished in failing human left ventricular myocardium and that downregulation of the Ca(2+)-transporting ATPase and phospholamban is not part of the molecular pathophysiology of dilated cardiomyopathy in humans.
Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction.
Authors: Cambien F , Costerousse O , Tiret L , Poirier O , Lecerf L , Gonzales M F , Evans A , Arveiler D , Cambou J P , Luc G 
Published: June 2012

BACKGROUND
The angiotensin-converting enzyme (ACE) plays an important role in the production of angiotensin II and the degradation of bradykinin, two peptides involved in cardiovascular homeostasy. Presence of a polymorphism in the ACE gene (ACE Ss) has been postulated from segregation analysis of plasma ACE in families. This putative polymorphism, which strongly affects the plasma and cellular levels of ACE, probably by modulating ACE gene transcription, has not yet been identified at the molecular level; however, an insertion/deletion polymorphism is present in the 16th intron of the ACE gene (ACE I/D) and appears to be a very good marker for ACE Ss. The biological role of ACE suggests that the ACE gene polymorphism could affect the predisposition to myocardial infarction (MI).

METHODS AND RESULTS
We have recently shown, in a large case-control study (ECTIM), that the marker allele D of the ACE gene, which is associated with higher levels of ACE in plasma and cells, was more frequent in male patients with MI than in control subjects, especially in patients considered at low risk. ACE activity has now been measured from frozen aliquots of plasma in a large subsample of the ECTIM study (n = 1086). Plasma ACE level did not differ between patients and control subjects in the older age group (> or = 55 years) but was higher in patients than in control subjects in the younger age group (< 55 years); P < .005 after adjustment on ACE I/D and other risk factors. In patients, plasma ACE levels decreased with age (R = -.225, P < 10(-4)), but in control subjects no such trend was observed. In the low-risk group (ApoB < 1.25 mg/dL, body mass index < 26 kg/m2, and not treated with hypolipidemic drugs), plasma ACE level was increased in patients when compared with control subjects among homozygotes and heterozygotes for the ACE I allele (P < .015). Analysis of the distribution of plasma ACE by using commingling analysis conditional on the marker genotype ACE I/D enabled us to infer the frequencies and effects of the postulated ACE Ss genotypes. The results suggest that the higher plasma ACE levels in patients than in control subjects in the younger age group were due to a difference in frequency of the postulated S allele (.47 versus .36).

CONCLUSIONS
These results extend our previous findings and indicate that plasma ACE level may be a risk factor for MI, independent of the ACE I/D polymorphism.
Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen Study.
Authors: Dekker J M , Schouten E G , Klootwijk P , Pool J , Kromhout D 
Published: June 2012

BACKGROUND
Heart-rate-adjusted QT-interval (QTc) is prognostic of sudden death in myocardial infarction patients. So far, population studies have yielded conflicting results on the predictive value of QTc for coronary heart disease morbidity and mortality. Therefore, we investigated this in a longitudinal study of middle-aged and elderly men.

METHODS AND RESULTS
From 1960 to 1985, 877 middle-aged men were followed and repeatedly examined in the Zutphen Study. In 1985 the remaining cohort was extended to 835 elderly men from the same birth cohort and followed until 1990. Men with prolonged QTc (420 ms1/2 or more) had a higher risk of myocardial infarction and coronary heart disease death relative to men with QTc less than 385 ms1/2. Age-adjusted coronary heart disease mortality rate ratios were 4.3 (95% confidence interval, 1.3 to 13.8) in middle-aged men and 3.3 (95% confidence interval, 1.0 to 11.6) in elderly men. These associations could not be attributed to prevalent heart disease and were independent of other cardiovascular risk factors.

CONCLUSIONS
These results indicate that within the normal range of QTc in the general population, men with long QTc are at higher risk for coronary heart disease. Because QTc is easily determined, it may provide a valuable contribution to risk stratification.