bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased Paraoxonase-2 Expression in Human Carotids During the Progression of Atherosclerosis
Authors: Fortunato Giuliana , Di Taranto Maria Donata , Bracale Umberto Marcello , Del Guercio Luca , Carbone Francesca , Mazzaccara Cristina , Morgante Alberto , D’Armiento Francesco Paolo , D’Armiento Maria , Porcellini Massimo , Sacchetti Lucia , Bracale Giancarlo , Salvatore Francesco
Published: February 2008

Objective—

Many gene products involved in oxidation and inflammation are implicated in the pathogenesis of atherosclerosis. We investigated paraoxonase 2 (PON2), 5-lipoxygenase (5-LO), and 5-LO activating protein (FLAP) expression and malondialdehyde (MDA) levels in carotid lesions to assess their involvement in plaque formation.

Methods and Results—

We measured gene expression and MDA levels in atherosclerotic plaques from 59 patients undergoing carotid endarterectomy, and in plaque-adjacent tissue from 41/59 patients. Twenty-three fetal carotids and 6 mammary arteries were also investigated. Real-time polymerase chain reaction and immunohistochemistry revealed decreased PON2 expression in plaques versus adjacent regions (
P
<0.005,
P
<0.001, respectively), mammary arteries (
P
<0.031,
P
<0.001, respectively), and fetal carotids (both
P
<0.001). mRNA levels of 5-LO and FLAP were higher (
P
<0.038,
P
<0.005, respectively) in lesions versus fetal carotids. MDA was higher in plaques versus plaque-adjacent tissue and fetal carotids. PON2 mRNA was downregulated by oxidative stress in 5 ex vivo experiments, thereby indicating its possible atheroprotection role.

Conclusions—

We demonstrate that PON2 mRNA and protein are decreased in plaques versus plaque-adjacent tissue, mammary arteries, and fetal carotids. Our data indicate that the protective effect of PON2 could fail during atherosclerosis exacerbation; this was confirmed by the increase of MDA levels. The increase of 5-LO and FLAP mRNA expression confirms their role as inflammatory markers associated to atherosclerosis.
Prothrombotic Gene Expression Profile in Vascular Smooth Muscle Cells of Human Saphenous Vein, but Not Internal Mammary Artery
Authors: Payeli S.K. , Latini R. , Gebhard C. , Patrignani A. , Wagner U. , Lüscher T.F. , Tanner F.C.
Published: February 2008

Background—

The resistance of internal mammary artery (IMA) toward thrombotic occlusion and accelerated atherosclerosis is not well understood. This study analyzed gene expression profiles of vascular smooth muscle cells (VSMCs) from IMA versus saphenous vein (SV).

Methods and Results—

54′675 probe sets were examined by Affymetrix microarrays. Thirty-one genes belonged to the coagulation system; 2 were differentially expressed, namely tissue factor (TF) and tissue-type plasminogen activator (tPA). TF was 3.1-fold lower in IMA than SV (
P
=0.006), whereas tPA was 9.0-fold higher (
P
<0.001). TF mRNA expression was lower in IMA than SV (
P
<0.05); tPA was higher (
P
<0.001). TF protein expression was 4.2±0.5-fold lower in IMA than SV (
P
<0.001); tPA was 2.6±0.4-fold higher (
P
<0.01). In IMA VSMC supernatant, TF protein and activity was lower (
P
<0.05), TFPI and tPA protein higher (
P
<0.05 and
P
<0.005), and clotting time of human plasma prolonged (
P
<0.05) as compared to SV. Migration to TF/FVIIa (10
−9
mol/L) was 3-fold lower in IMA than SV (
P
=0.01); PAR-2 protein expression was similar (
P
=NS), PAR-2 blockade without effect (
P
=NS).

Conclusions—

Among the genes of the coagulation system, TF and tPA are differentially expressed in VSMCs from IMA versus SV. This is consistent with protection of IMA from thrombus formation and vascular remodeling.
PICOT Attenuates Cardiac Hypertrophy by Disrupting Calcineurin–NFAT Signaling
Authors: Jeong Dongtak , Kim Ji Myoung , Cha Hyeseon , Oh Jae Gyun , Park Jaeho , Yun Soo-Hyeon , Ju Eun-Seon , Jeon Eun-Seok , Hajjar Roger J. , Park Woo Jin
Published: February 2008

PICOT (protein kinase C–interacting cousin of thioredoxin) was previously shown to inhibit pressure overload-induced cardiac hypertrophy, concomitant with an increase in ventricular function and cardiomyocyte contractility. The combined analyses of glutathione
S
-transferase pull-down experiments and mass spectrometry enabled us to determine that PICOT directly interacts with muscle LIM protein (MLP) via its carboxyl-terminal half (PICOT-C). It was also shown that PICOT colocalizes with MLP in the Z-disc. MLP is known to play a role in anchoring calcineurin to the Z-disc in the sarcomere, which is critical for calcineurin–NFAT (nuclear factor of activated T cells) signaling. We, therefore, suggested that PICOT may affect calcineurin–NFAT signaling through its interaction with MLP. Consistent with this hypothesis, PICOT, or more specifically PICOT-C, abrogated phenylephrine-induced increases in calcineurin phosphatase activity, NFAT dephosphorylation/nuclear translocation, and NFAT-dependent transcriptional activation in neonatal cardiomyocytes. In addition, pressure overload–induced upregulation of NFAT target genes was significantly diminished in the hearts of PICOT-overexpressing transgenic mice. PICOT interfered with MLP–calcineurin interactions in a dose-dependent manner. Moreover, calcineurin was displaced from the Z-disc, concomitant with an abrogated interaction between calcineurin and MLP, in the hearts of PICOT transgenic mice. Replenishment of MLP restored the hypertrophic responses and the increase in calcineurin phosphatase activity that was inhibited by PICOT in phenylephrine-treated cardiomyocytes. Finally, PICOT-C inhibited cardiac hypertrophy to an extent that was comparable to that of full-length PICOT. Taken together, these data suggest that PICOT inhibits cardiac hypertrophy largely by negatively regulating calcineurin–NFAT signaling via disruption of the MLP–calcineurin interaction.
Angiotensin II–Inducible Platelet-Derived Growth Factor-D Transcription Requires Specific Ser/Thr Residues in the Second Zinc Finger Region of Sp1
Authors: Tan Nicole Y. , Midgley Valerie C. , Kavurma Mary M. , Santiago Fernando S. , Luo Xiao , Peden Ryan , Fahmy Roger G. , Berndt Michael C. , Molloy Mark P. , Khachigian Levon M.
Published: February 2008

Sp1, the first identified and cloned transcription factor, regulates gene expression via multiple mechanisms including direct protein–DNA interactions, protein–protein interactions, chromatin remodeling, and maintenance of methylation-free CpG islands. Sp1 is itself regulated at different levels, for example, by glycosylation, acetylation, and phosphorylation by kinases such as the atypical protein kinase C-ζ. Although Sp1 controls the basal and inducible regulation of many genes, the posttranslational processes regulating its function and their relevance to pathology are not well understood. Here we have used a variety of approaches to identify 3 amino acids (Thr668, Ser670, and Thr681) in the zinc finger domain of Sp1 that are modified by PKC-ζ and have generated novel anti-peptide antibodies recognizing the PKC-ζ–phosphorylated form of Sp1. Angiotensin II, which activates PKC-ζ phosphorylation (at Thr410) via the angiotensin II type 1 receptor, stimulates Sp1 phosphorylation and increases Sp1 binding to the platelet-derived growth factor-D promoter. All 3 residues in Sp1 (Thr668, Ser670, and Thr681) are required for Sp1-dependent platelet-derived growth factor-D activation in response to angiotensin II. Immunohistochemical analysis revealed that phosphorylated Sp1 is expressed in smooth muscle cells of human atherosclerotic plaques and is dynamically expressed together with platelet-derived growth factor-D in smooth muscle cells of the injured rat carotid artery wall. This study provides new insights into the regulatory mechanisms controlling the PKC-ζ–phospho-Sp1 axis and angiotensin II–inducible gene expression.
Lipoprotein-Associated Phospholipase A
2
, Hormone Use, and the Risk of Ischemic Stroke in Postmenopausal Women
Authors: Wassertheil-Smoller Sylvia , Kooperberg Charles , McGinn Aileen P. , Kaplan Robert C. , Hsia Judith , Hendrix Susan L. , Manson JoAnn E. , Berger Jeffrey S. , Kuller Lewis H. , Allison Matthew A. , Baird Alison E.
Published: February 2008

Few studies have investigated the role of elevated lipoprotein-associated phospholipase A2 (Lp-PLA
2
) with stroke risk, and those that have are based on small numbers of strokes. No study has evaluated the effect of hormone therapy use on the association of Lp-PLA
2
and stroke. We assessed the relationship between Lp-PLA
2
and the risk of incident ischemic stroke in 929 stroke patients and 935 control subjects in the Hormones and Biomarkers Predicting Stroke Study, a nested case-control study from the Women’s Health Initiative Observational Study. Mean (SD) levels of Lp-PLA
2
were significantly higher among case subjects (309.0 [97.1]) than control subjects (296.3 [87.3];
P
<0.01). Odds ratio for ischemic stroke for the highest quartile of Lp-PLA
2
, compared with lowest, controlling for multiple covariates, was 1.08 (95% CI: 0.75 to 1.55). However, among 1137 nonusers of hormone therapy at baseline, the corresponding odds ratio was 1.55 (95% CI: 1.05 to 2.28),whereas there was no significant association among 737 hormone users (odds ratio: 0.70; 95% CI: 0.42 to 1.17;
P
for interaction=0.055). Moreover, among nonhormone users, women with high C-reactive protein and high Lp-PLA2 had more than twice the risk of stroke (odds ratio: 2.26; 95% CI: 1.55 to 3.35) compared with women low levels in both biomarkers. Furthermore, different stroke cases were identified as high risk by Lp-PLA
2
rather than by C-reactive protein. Lp-PLA
2
was associated with incident ischemic stroke independently of C-reactive protein and traditional cardiovascular risk factors among nonusers of hormone therapy with highest risk in those who had both high C-reactive protein and high Lp-PLA
2
.
Alcohol Consumption and the Risk of Hypertension in Women and Men
Authors: Sesso Howard D. , Cook Nancy R. , Buring Julie E. , Manson JoAnn E. , Gaziano J. Michael
Published: February 2008

Heavy alcohol intake increases the risk of hypertension, but the relationship between light-to-moderate alcohol consumption and incident hypertension remains controversial. We prospectively followed 28 848 women from the Women’s Health Study and 13 455 men from the Physicians’ Health Study free of baseline hypertension, cardiovascular disease, and cancer. Self-reported lifestyle and clinical risk factors were collected. In women, total alcohol intake was summed from liquor, red wine, white wine, and beer; men reported total alcohol intake from a single combined question. During 10.9 and 21.8 years of follow-up, 8680 women and 6012 men developed hypertension (defined as new physician diagnosis, antihypertensive treatment, reported systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg). In women, we found a J-shaped association between alcohol intake and hypertension in age- and lifestyle-adjusted models. Adding potential intermediates (body mass index, diabetes, and high cholesterol) attenuated the benefits of alcohol in the light-to-moderate range and strengthened the adverse effects of heavy alcohol intake. Beverage-specific relative risks paralleled those for total alcohol intake. In men, alcohol intake was positively and significantly associated with the risk of hypertension and persisted after multivariate adjustment. Models stratified by baseline systolic blood pressure (<120 versus ≥120 mm Hg) or diastolic blood pressure (<75 versus ≥75 mm Hg) did not alter the relative risks in women and men. In conclusion, light-to-moderate alcohol consumption decreased hypertension risk in women and increased risk in men. The threshold above which alcohol became deleterious for hypertension risk emerged at ≥4 drinks per day in women versus a moderate level of ≥1 drink per day in men.
Gender Difference in Blood Pressure Control and Cardiovascular Risk Factors in Americans With Diagnosed Hypertension
Authors: Ong Kwok Leung , Tso Annette W.K. , Lam Karen S.L. , Cheung Bernard M.Y.
Published: February 2008

Hypertension is an important risk factor for cardiovascular disease, which is the leading cause of death in women. We, therefore, analyzed gender-specific trends in the control of blood pressure and prevalence of 5 other cardiovascular risk factors (central obesity, elevated total cholesterol, low high-density lipoprotein cholesterol, hyperglycemia, and smoking) among adults with diagnosed hypertension in the United States. We included 3475 participants aged ≥18 years with diagnosed hypertension in the National Health and Nutrition Examination Survey 1999–2004. The age-adjusted prevalence of uncontrolled blood pressure was 50.8±2.1% in men and 55.9±1.5% in women, which were not significantly different and had not changed significantly with time. Central obesity, elevated total cholesterol level, and low high-density lipoprotein cholesterol were significantly more prevalent in women than in men (79.0±1.0%, 61.3±1.6%, and 39.7±1.6% versus 63.9±1.6%, 48.1±1.8%, and 35.6±1.7%, respectively;
P
<0.05). The age-adjusted proportion with ≥3 of the 6 risk factors studied was higher in women than in men (52.5±1.4% versus 40.9±1.8%;
P
<0.001), and this proportion decreased significantly by 7.7% in women from 1999–2000 to 2003–2004 (
P
<0.05) but not in men. Our study shows that blood pressure control in women with diagnosed hypertension was not significantly inferior compared with men and had not changed significantly in 1999–2004. However, women had higher prevalence of other concomitant cardiovascular risk factors. Although there is room for improvement in blood pressure control, our study has highlighted the importance of addressing concomitant cardiovascular risk factors in women with hypertension.
Proteasome Activity as a Target of Hormone Replacement Therapy–Dependent Plaque Stabilization in Postmenopausal Women
Authors: Marfella Raffaele , Di Filippo Clara , Portoghese Michele , Ferraraccio Franca , Crescenzi Basilio , Siniscalchi Mario , Barbieri Michelangela , Bologna Carolina , Rizzo Maria Rosaria , Rossi Francesco , D’Amico Michele , Paolisso Giuseppe
Published: February 2008

The molecular mechanisms of the atheroprotective effect evoked by hormone replacement therapy in postmenopausal women is not well known. Recently, we have demonstrated enhanced activity of the ubiquitin-proteasome system in human atherosclerotic plaques and evidenced that it is associated with inflammatory-induced plaque rupture. Therefore, we hypothesized that hormone replacement therapy may exert the cardioprotective effects modulating the ubiquitin-proteasome activity. To investigate this possibility, this study examined the differences in inflammatory infiltration, as well as ubiquitin-proteasome activity, between asymptomatic carotid plaques of postmenopausal women with and without concomitant hormone replacement therapy. Plaques were obtained from 20 postmenopausal women treated with hormone replacement therapy (current users) and 32 nontreated women (never-users) enlisted to undergo carotid endarterectomy for extracranial high-grade (>70%) internal carotid artery stenosis. Plaques were analyzed for macrophages, T lymphocytes, human leukocyte antigen-DR+ cells, ubiquitin-proteasome system, nuclear factor κB, inhibitor of nuclear factor κBβ, tumor necrosis factor-α, nitrotyrosine, matrix metalloproteinase-9, and collagen content (immunohistochemistry and ELISA). Compared with plaques from current users, plaques from never-users had more macrophages, T lymphocytes, and human leukocyte antigen-DR+ cells (
P
<0.001); more ubiquitin-proteasome activity, tumor necrosis factor-α, and nuclear factor κB (
P
<0.001); and more nitrotyrosine and matrix metalloproteinase-9 (
P
<0.001), along with a lesser collagen content and inhibitor of nuclear factor κBβ levels (
P
<0.001). This study supports the hypothesis that hormone replacement therapy inhibits plaque ubiquitin-proteasome activity by decreasing oxidative stress generation in postmenopausal women. This effect, in turn, might contribute to plaque stabilization by inhibiting the activation of nuclear factor κB–dependent inflammation, responsible for plaque rupture.
Total Vascular Resistance and Left Ventricular Morphology as Screening Tools for Complications in Pregnancy
Authors: Vasapollo Barbara , Novelli Gian Paolo , Valensise Herbert
Published: February 2008

We evaluated the predictive value of elevated total vascular resistance on the outcome of pregnancy in normotensive high-risk primigravidas with bilateral notching of the uterine artery Doppler. A total of 526 high-risk primigravidas referred to the obstetrics outpatient clinic of Tor Vergata University with bilateral notching of the uterine artery at 20 to 22 weeks’ gestation were submitted to a maternal echocardiographic examination and uterine artery Doppler evaluation at 24 weeks’ gestation. Blood pressure was recorded at the time of the examination, total vascular resistance was calculated, and the geometric pattern of the left ventricle was assessed. Patients were followed until the end of pregnancy to detect fetal/maternal adverse outcomes (gestational hypertension, preeclampsia, abruptio placentae, fetal growth restriction, perinatal death, etc). A total of 111 of the 526 pregnancies showed a bilateral notch at 24 weeks’ gestation, and 97 had an adverse outcome (18.44%). The best independent predictor for maternal and fetal complications was total vascular resistance (odds ratio: 91.25; 95% CI: 39.64 to 210.05;
P
<0.001). The cutoff value was 1400 dynes · s · cm
−5
, with a sensitivity and a specificity of 89% and 94%, respectively. A high relative wall thickness of the left ventricle (>0.37; odds ratio: 2.47; 95% CI: 1.12 to 5.44) and a hypertrophized ventricle (left ventricular mass >130 g; odds ratio: 2.52; 95% CI: 1.12 to 5.64) were also independent predictors (
P
<0.05). Echocardiography might identify at 24 weeks’ gestation patients who subsequently develop maternal and fetal complications through the assessment of maternal hemodynamics and left ventricular geometry.
Smaller Aortic Dimensions Do Not Fully Account for the Greater Pulse Pressure in Elderly Female Hypertensives
Authors: Dart Anthony M. , Kingwell Bronwyn A. , Gatzka Christoph D. , Willson Kristyn , Liang Yu-Lu , Berry Karen L. , Wing Lindon M.H. , Reid Christopher M. , Ryan Philip , Beilin Lawrence J. , Jennings Garry L.R. , Johnston Colin I. , McNeil John J. , MacDonald Graham J. , Morgan Trefor O. , West Malcolm J. , Cameron James D.
Published: February 2008

This study examined the importance of aortic dimensions in determining pulse pressure in elderly hypertensives participating in the 2nd Australian National Blood Pressure Study, including a substantial number not previously receiving blood pressure lowering medication. Aortic dimensions were determined by ultrasound at the transverse arch and at the insertion of the aortic valve. Unadjusted data showed negative (
P
<0.001) correlations between central (carotid) and (brachial) peripheral pulse pressure and both arch (−0.200, −0.181) and outflow tract (−0.238, −0.238) diameters. Correlations were similar in those previously treated with blood pressure lowering medication and in the treatment naïve. Central pulse pressure (84±26 versus 75±28 mm Hg,
P
<0.001) was higher and aortic dimensions (transverse arch 2.56±0.31 versus 2.88±0.35 mm,
P
<0.001) smaller in women than men. Women had greater aortic stiffness (beta index 29.4±36.1 versus 22.1±21.3,
P
<0.03). Other bivariate correlates of central pulse pressure were age, mean arterial pressure, height, heart rate, augmentation index, aortic stiffness (all
P
<0.001), and weight (
P
=0.027). In multivariate analyses gender remained a predictor of central pulse pressure (
P
<0.001) even with inclusion of aortic dimensions (
P
=0.013) height and weight. Other significant terms were age, heart rate, mean blood pressure, and aortic stiffness (all
P
<0.001). These findings demonstrate an independent inverse relation between aortic size and pulse pressure in older hypertensive subjects. Differences in aortic dimensions and stiffness between genders do not fully account for the observed blood pressure differences, suggesting that a contributory factor to gender differences in pulse pressure is an increased age-related mismatch in ventricular function and aortic stiffness in women compared with men.
Medroxyprogesterone Abrogates the Inhibitory Effects of Estradiol on Vascular Smooth Muscle Cells by Preventing Estradiol Metabolism
Authors: Dubey Raghvendra K. , Jackson Edwin K. , Gillespie Delbert G. , Zacharia Lefteris C. , Wunder Dorothea , Imthurn Bruno , Rosselli Marinella
Published: February 2008

Sequential conversion of estradiol (E) to 2/4-hydroxyestradiols and 2-/4-methoxyestradiols (MEs) by CYP450s and catechol-
O
-methyltransferase, respectively, contributes to the inhibitory effects of E on smooth muscle cells (SMCs) via estrogen receptor–independent mechanisms. Because medroxyprogesterone (MPA) is a substrate for CYP450s, we hypothesized that MPA may abrogate the inhibitory effects of E by competing for CYP450s and inhibiting the formation of 2/4-hydroxyestradiols and MEs. To test this hypothesis, we investigated the effects of E on SMC number, DNA and collagen synthesis, and migration in the presence and absence of MPA. The inhibitory effects of E on cell number, DNA synthesis, collagen synthesis, and SMC migration were significantly abrogated by MPA. For example, E (0.1μmol/L) reduced cell number to 51±3.6% of control, and this inhibitory effect was attenuated to 87.5±2.9% by MPA (10 nmol/L). Treatment with MPA alone did not alter any SMC parameters, and the abrogatory effects of MPA were not blocked by RU486 (progesterone-receptor antagonist), nor did treatment of SMCs with MPA influence the expression of estrogen receptor-α or estrogen receptor-β. In SMCs and microsomal preparations, MPA inhibited the sequential conversion of E to 2–2/4-hydroxyestradiol and 2-ME. Moreover, as compared with microsomes treated with E alone, 2-ME formation was inhibited when SMCs were incubated with microsomal extracts incubated with E plus MPA. Our findings suggest that the inhibitory actions of MPA on the metabolism of E to 2/4-hydroxyestradiols and MEs may negate the cardiovascular protective actions of estradiol in postmenopausal women receiving estradiol therapy combined with administration of MPA.
Prolonged Ovarian Hormone Deprivation Impairs the Protective Vascular Actions of Estrogen Receptor αAgonists
Authors: Pinna Christian , Cignarella Andrea , Sanvito Paola , Pelosi Valeria , Bolego Chiara
Published: February 2008

The vascular consequences of estrogen treatment may be driven by its initiation timing. We tested the hypothesis that the duration of ovarian hormone deprivation before estrogen reintroduction affects the role of estrogen as mediator of endothelial function and vascular relaxation in nondiseased vessels. Rats were ovariectomized and implanted with 17β-estradiol (E
2
) or oil capsules 1, 4, and 8 months after surgery. After the longest hypoestrogenicity period, acetylcholine-mediated aortic relaxation was attenuated and insensitive to E
2
administration despite endothelial integrity. Whereas no rapid vasorelaxant responses were elicited by an estrogen receptor (ER) β–selective agonist, responses to E
2
and an ERα selective agonist waned postovariectomy at any given time and were restored by E
2
treatment after 1 and 4 months but not 8 months postovariectomy. Accordingly, endothelial ERα mRNA and protein expression declined ≈6-fold after prolonged hypoestrogenicity and was restored by estrogen replacement starting 1 month but not 8 months postovariectomy. Furthermore, the amount of active phosphorylated endothelial NO synthase rose significantly after E
2
replacement after 1 and 4 months but not 8 months postovariectomy. The present findings document that the functional impairment of the ERα/endothelial NO synthase signaling network after an extended period of hypoestrogenicity was not restored by E
2
administration, providing experimental support to early initiation of estrogen replacement with preferential ERα targeting to improve cardiovascular outcomes.
Sex Differences in the Pressor Response to Angiotensin II When the Endogenous Renin-Angiotensin System Is Blocked
Authors: Sartori-Valinotti Julio C. , Iliescu Radu , Yanes Licy L. , Dorsett-Martin Wanda , Reckelhoff Jane F.
Published: February 2008

The present study determined whether there are sex differences in the pressor response to angiotensin II (Ang II) when the endogenous renin-angiotensin system (RAS) is blocked by enalapril (ACEI), and whether this pressor response is changed in the presence of high salt (HS). Telemetry BP was measured in rats treated with ACEI (250 mg/L drinking water) (n=6 to 7/grp), or with ACEI and Ang II (150 ng/kg/min, sc; n=5 to 6/grp), for 3 wk. For the last 2 wk of the study, rats received HS (4% NaCl). MAP was lower in females during baseline (100.8±1.1 versus 105.2±1.3;
P
<0.05), and with ACEI the last 3 days on normal salt diet (78.8±1.2 versus 88.5±0.9;
P
<0.05), but increased to higher levels than in males on day 6 of Ang II (129.0±2.2 versus 117.3±2.9;
P
<0.05). One week of Ang II increased albuminuria in males, but not females, and urinary 8-iso-PGF2α (F2-isoP) was not increased in either males or females. MAP was salt-sensitive in both sexes receiving ACEI, but was only salt-sensitive in males with Ang II (129.3±3.7 versus 145.1±5.7;
P
<0.05). Albuminuria continued to increase with HS and Ang II in males, but not in females. F2-isoP excretion increased with MAP during the last week of HS and Ang II in males but was independent of MAP in females. With ACEI, MAP in females on normal salt is more responsive to Ang II but is independent of oxidative stress or renal injury. MAP in males is salt-sensitive with Ang II, which may be mediated by oxidative stress and renal injury.
Gender Disparities in Blood Pressure Control and Cardiovascular Care in a National Sample of Ambulatory Care Visits
Authors: Keyhani Salomeh , Scobie Janice V. , Hebert Paul L. , McLaughlin Mary Ann
Published: February 2008

The purpose of this study was to provide an analysis of gender-based disparities in hypertension and cardiovascular disease care in ambulatory practices across the United States. Using data from the 2005 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, we conducted a cross-sectional analysis of patient visits with their primary care providers and examined the association between gender and blood pressure control, use of any antihypertensive medication or initiation of new therapy for patients with uncontrolled hypertension, and receipt of recommended therapy for select cardiovascular conditions. Multivariable models were estimated to examine the association between gender and each outcome controlling for other variables. A total of 12 064 patient visits were identified (7786 women and 4278 men). Among patients with hypertension, women were less likely than men to meet blood pressure control targets (54.0% versus 58.7%;
P
<0.02). In multivariate analyses, women aged 65 to 80 years were less likely than men to have controlled hypertension (odds ratio: 0.62; 95% CI: 0.45 to 0.85). There was no association between gender and use of any antihypertensive medication or initiating a new therapy among patients with uncontrolled hypertension. In multivariate analyses, women were less likely than men to receive aspirin (odds ratio: 0.43; 95% CI: 0.27 to 0.67) and β-blockers (odds ratio: 0.60; 95% CI: 0.36 to 0.99) for secondary prevention of cardiovascular disease. Our study highlights the persistent gender disparities in blood pressure control and cardiovascular disease management and also reveals the inadequate delivery of cardiovascular care to all patients.
Dietary Intake of Dairy Products, Calcium, and Vitamin D and the Risk of Hypertension in Middle-Aged and Older Women
Authors: Wang Lu , Manson JoAnn E. , Buring Julie E. , Lee I-Min , Sesso Howard D.
Published: February 2008

Prospective data on the associations between intake of dairy products and its nutrient components with risk of hypertension remain limited. We therefore investigated the associations of intake of dairy products, calcium, and vitamin D with the incidence of hypertension in a prospective cohort of 28 886 US women aged ≥45 years. Intake of dairy products, calcium, and vitamin D at baseline were assessed from semiquantitative food frequency questionnaires. Incident cases of hypertension (n=8710) were identified from annual follow-up questionnaires during 10 years of follow-up. After adjusting for major hypertension risk factors, the relative risks of incident hypertension across increasing quintiles of low-fat dairy product intake were 1.00 (reference), 0.98, 0.97, 0.95, and 0.89 (
P
for trend: 0.001). The risk of hypertension decreased in the higher quintiles of dietary calcium (multivariate relative risk in the highest quintile: 0.87) and dietary vitamin D (multivariate relative risk in the highest quintile: 0.95), but did not change with calcium or vitamin D supplements. Adjustment for dietary calcium significantly attenuated the inverse association of low-fat dairy intake with risk of hypertension, whereas adjustment for dietary vitamin D did not change the association. The multivariate relative risks across increasing quintiles of high-fat dairy product intake, in contrast, were 1.00, 1.02, 1.01, 1.00, and 0.97 (
P
for trend: 0.17). Our study found that intakes of low-fat dairy products, calcium, and vitamin D were each inversely associated with risk of hypertension in middle-aged and older women, suggesting their potential roles in the primary prevention of hypertension and cardiovascular complications.
Relationship of Ankle Blood Pressures to Cardiovascular Events in Older Adults
Authors: Sutton-Tyrrell Kim , Venkitachalam Lakshmi , Kanaya Alka M. , Boudreau Robert , Harris Tamara , Thompson Trina , Mackey Rachel H. , Visser Marjolein , Vaidean Georgeta D. , Newman Anne B.
Published: February 2008

Background and Purpose—

Low values of ankle–arm systolic blood pressure ratio predict mortality and cardiovascular events. High values, associated with arterial calcification, also carry risk for mortality. We focus on the extent to which low and high ankle–arm index values as well as noncompressible arteries are associated with mortality and cardiovascular events, including stroke in older adults.

Methods—

We followed 2886 adults aged 70 to 79 for a mean of 6.7 years for vital status and cardiovascular events (coronary heart disease, stroke, and congestive heart failure).

Results—

Normal ankle–arm index values of 0.91 to 1.3 were found in 80%, low values of ≤0.9 were found in 13%, high values of >1.3 were obtained in 5%, and noncompressible arteries were found in 2% of the group. Increased mortality was associated with both low and high ankle–arm index values beginning at levels of <1.0 or ≥1.4. Subjects with low ankle–arm index values or noncompressible arteries had significantly higher event rates than those with normal ankle blood pressures for all end points. For coronary heart disease, hazard ratios associated with a low ankle–arm index, high ankle–arm index, and noncompressible arteries were 1.4, 1.5, and 1.7 (
P
<0.05 for all) after controlling for age, gender, race, prevalent cardiovascular disease, diabetes, and major cardiovascular risk factors. Noncompressible arteries carried a particularly high risk of stroke and congestive heart failure (hazard ratio=2.1 and 2.4, respectively).

Conclusions—

Among older adults, low and high ankle–arm index values carry elevated risk for cardiovascular events. Noncompressible leg arteries carry elevated risk for stroke and congestive heart failure specifically.
Linking MRI Hyperintensities With Patterns of Neuropsychological Impairment
Authors: Libon David J. , Price Catherine C. , Giovannetti Tania , Swenson Rodney , Bettcher Brianne Magouirk , Heilman Kenneth M. , Pennisi Alfio
Published: February 2008

Background and Purpose—

Leukoaraiosis (LA) might interrupt intra- and interhemispheric communication and thus induce cognitive impairments and dementia. It remains unclear, however, if there is a volume threshold of LA that is needed before either the signs of dementia and/or a specific pattern of neuropsychological impairment become manifest. Roman et al has suggested that 25% of white matter may need to be involved before white matter alterations influence the clinical signs associated with dementia. The purpose of this study is to ascertain the threshold of MRI-LA as measured with a visual rating scale needed to induce specific patterns of neuropsychological impairment associated with dementia.

Methods—

One hundred fifteen patients with dementia received a comprehensive neuropsychological examination and the severity of MRI-LA was measured using a 40-point LA scale.

Results—

Patients were categorized into low (mean LA=4.21±2.92; 3.22%–17.82%), moderate (mean LA=12.58±2.54; 25.01%–37.80%), and severe (mean LA=22.36±4.04; 45.80%–66.00%) LA groups. Patients in the mild LA group obtained markedly lower scores on tests of episodic memory compared with working memory, a neuropsychological profile often associated with Alzheimer disease. Patients with moderate LA displayed equal impairment on neuropsychological tests. Patients in the severe LA group obtained significantly lower scores on tests of working memory as compared with episodic memory.

Conclusions—

These data provide evidence that a threshold of moderate MRI-LA as measured with a visual rating scale is associated with greater and/or equal impairment on tests of working memory versus episodic memory and provides a benchmark to assess the effect of MRI-LA on the clinical presentation of dementia.
Impact of Restricting Enrollment in Stroke Genetics Research to Adults Able to Provide Informed Consent
Authors: Chen Donna T. , Case L. Douglas , Brott Thomas G. , Brown Robert D. , Silliman Scott L. , Meschia James F. , Worrall Bradford B.
Published: February 2008

Background and Purpose—

The extent of potential consent bias in observational studies elucidating genetic and environmental contributions to ischemic stroke is largely unknown. The purpose of this study was to assess differences in stroke cohort characteristics between those who provided informed consent and those whose enrollment was authorized by surrogate decision makers.

Methods—

The Ischemic Stroke Genetics Study (ISGS) is a prospective, 5-center, case-control study of first-ever ischemic stroke. Demographic, clinical, and stroke characteristics were compared between cases enrolled by self versus by surrogate. Data from one site that limits enrollment only to those able to self-consent were also analyzed to compare those who enrolled with those not able to consent.

Results—

Overall, 10% (54 of 517) were enrolled using surrogate authorization. Self-consented and surrogate-authorized cases did not differ significantly in age, sex, or conventional risk factors. Surrogate-authorized cases had significantly more severe stroke deficits, larger infarcts, and infarcts localizing to left supratentorial regions. Similarly, at the site restricting enrollment, stroke severity and characteristics differed between self-consented individuals and those otherwise eligible but unable to provide consent.

Conclusions—

Failure to permit surrogate authorization in genetic studies of ischemic stroke may skew enrollment toward less severe strokes caused by smaller infarcts. This potential consent bias may undermine the ability to identify genetic determinants of risk and severity and suggests that surrogate enrollment in these studies can be ethically justifiable.
Delayed Treatment With Minocycline Ameliorates Neurologic Impairment Through Activated Microglia Expressing a High-Mobility Group Box1–Inhibiting Mechanism
Authors: Hayakawa Kazuhide , Mishima Kenichi , Nozako Masanori , Hazekawa Mai , Mishima Shohei , Fujioka Masayuki , Orito Kensuke , Egashira Nobuaki , Iwasaki Katsunori , Fujiwara Michihiro
Published: February 2008

Background and Purpose—

Minocycline, a semisynthetic tetracycline antibiotic, has been reported to ameliorate brain injury and inhibit microglial activation after focal cerebral ischemia. However, the cerebroprotective mechanism of minocycline remains unclear. In the present study, we investigated that mechanism of minocycline in a murine model of 4-hour middle cerebral artery (MCA) occlusion.

Methods—

One day after 4-hour MCA occlusion, minocycline was administered intraperitoneally for 14 days. Neurologic scores were measured 1, 7, and 14 days after cerebral ischemia. Motor coordination was evaluated at 14 days by the rota-rod test at 10 rpm. Activated microglia and high-mobility group box1 (HMGB1), a cytokine-like mediator, were also evaluated by immunostaining and Western blotting. In addition, terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling immunostaining was carried out 14 days after cerebral ischemia.

Results—

Repeated treatment with minocycline (1, 5, and 10 mg/kg) for 14 days improved neurologic score, motor coordination on the rota-rod test, and survival in a dose-dependent manner. Minocycline decreased the expression of Iba1, a marker of activated microglia, as assessed by both immunostaining and Western blotting. Moreover, minocycline decreased the activation of microglia expressing HMGB1 within the brain and also decreased both brain and plasma HMGB1 levels. Additionally, minocycline significantly decreased the number of terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling–positive cells and prevented ischemic brain atrophy 14 days after cerebral ischemia.

Conclusions—

Our results suggest that minocycline inhibits activated microglia expressing HMGB1 and decreases neurologic impairment induced by cerebral ischemia. Minocycline will have a palliative action and open new therapeutic possibilities for treatment of postischemic injury via an HMGB1-inhibiting mechanism.
Endovascular Treatment of Unruptured Intracranial Aneurysms With Guglielmi Detachable Coils
Authors: Standhardt Harald , Boecher-Schwarz Hans , Gruber Andreas , Benesch Thomas , Knosp Engelbert , Bavinzski Gerhard
Published: February 2008

Background and Purpose—

Purpose of the present study is to evaluate the clinical outcome of endovascular treatment of unruptured intracranial aneurysms and to address the question of long-term stability and protection against future subarachnoid hemorrhage.

Methods—

Retrospective analysis of all patients treated in a 12-year period (173 patients: age 26 to 76 yr, mean 52.2±10.8/202 aneurysms: size 3 to 50 mm, mean 10.0±8.3).

Results—

The mortality was 0.5%; the overall morbidity was 3.5%. The most frequent complications were thromboembolic events (10.9%). Of these, 3.0% of patients suffered a stroke, leading to severe disability in 1 patient (0.5%). In 1 patient, the aneurysm ruptured during treatment, resulting in relevant neurological disability. Another patient suffered a fatal aneurysm rupture hours after treatment. The occlusion rate depended on aneurysm and neck size. Follow-up angiography revealed a decrease of the occlusion rate over time. This trend was obvious in all size categories and was most pronounced in giant aneurysms. In 3 patients (1.5%) with partially thrombosed giant aneurysms of the posterior circulation, embolization could not prevent later aneurysm rupture. There were no ruptures of any other aneurysms in the follow-up period (3.7±3.4 yr).

Conclusion—

Endovascular treatment is a highly safe procedure with low intervention-related morbidity and mortality. Long-term data for nongiant aneurysms showed good protection against rupture in the observation period. In contrast, the risk of rupture for giant aneurysms of the posterior circulation was as high as expected in observational studies.
Nonaspirin Nonsteroidal Anti-inflammatory Drugs and Hemorrhagic Stroke Risk
Authors: Choi Nam-Kyong , Park Byung-Joo , Jeong Sang-Wuk , Yu Kyung-Ho , Yoon Byung-Woo
Published: February 2008

Background and Purpose—

The relationship between nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and hemorrhagic stroke (HS) remains unclear. We examined the risk of HS associated with the use of NANSAIDs in Koreans.

Methods—

We performed a nationwide, multicenter case-control study from 2002 to 2004. This study included 940 nontraumatic acute HS cases in patients aged 30 to 84 years, with an absence of a history of stroke or hemorrhage-prone brain lesions, alongside 940 community controls, matched to each case by age and sex. Pretrained interviewers obtained information on prescription drugs as well as over-the-counter drugs taken within 14 days before the onset of stroke. We adjusted potential confounders, including family histories of stroke, histories of hypertension, smoking, alcohol consumption, high salt intake, and laborious work hours. The adjusted ORs and their 95% CIs were calculated by conditional logistic regression.

Results—

The proportion of NANSAIDs exposure within 14 days was 2.9% for HS patients and 2.0% for the controls. The adjusted odds ratios of stroke in NANSAIDs users compared with nonusers was 1.12 (95% CI, 0.77 to 1.65) for all HS, 1.03 (95% CI, 0.49 to 2.18) for subarachnoid hemorrhage, and 1.19 (95% CI, 0.76 to 1.87) for intracerebral hemorrhage.

Conclusions—

No increased risk of HS either subarachnoid hemorrhage or intracerebral hemorrhage was found among NANSAIDs users.
MicroRNA Expression in the Blood and Brain of Rats Subjected to Transient Focal Ischemia by Middle Cerebral Artery Occlusion
Authors: Jeyaseelan Kandiah , Lim Kai Ying , Armugam Arunmozhiarasi
Published: February 2008

Background and Purpose—

Several hundred small RNAs called microRNAs (miRNAs) have been identified and characterized from various organisms, including humans. In humans, some of these miRNAs have been found to regulate (patho)physiologic conditions such as tumor progression/regression, cholesterol and glucose homeostasis, etc. In this report, we present data on the miRNAs expressed under ischemic conditions in both the brain and blood of rats subjected to middle cerebral artery occlusion (MCAo).

Methods—

Sprague-Dawley rats subjected to MCAo were reperfused for either 24 or 48 hours, and both blood and brain samples were harvested. miRNA expression profiling and oligonucleotide microarray were carried out, and the data were validated by quantitative real-time polymerase chain reaction and correlated with published data on protein and gene expression in MCAo rats.

Results—

We report here for the first time the involvement of miRNA regulation in brain pathogenesis associated with MCAo. Comparison with the corresponding DNA microarray data revealed that the target mRNA expression is correlated with the regulation of miRNA. We have also provided evidence that some of the miRNAs that are highly expressed in the ischemic brain can be detected in blood samples.

Conclusions—

Further studies are needed to evaluate the possible use of miRNAs as biomarkers in stroke and related pathologies.
Utilizing the Theory of Planned Behavior to Inform Change Management
Authors: Jimmieson Nerina L. , Peach Megan , White Katherine M.
Published: February 2008

Utilizing the theory of planned behavior (TPB) as a framework for understanding employee intentions to support organizational change, this study examined the extent to which attitude, subjective norm, and perceived behavioral control (PBC) and the interactive effect of group norm and ingroup identification predicted intentions to carry out change-supportive activities. It also was hypothesized that communication and participation would increase intentions, with these relationships mediated by the TPB variables. The sample was 149 employees undergoing the first phase of a building relocation. Attitude, subjective norm, and PBC each predicted intentions. A significant interaction emerged, with group norm predicting intentions only for employees who identified strongly with their reference group. Employees who perceived sufficient information about the relocation reported stronger intentions, an effect that was partially mediated via subjective norm and PBC. Similarly, participation predicted intentions via subjective norm. Implications for fostering employee readiness for change are discussed.
Examining the Cultural Specificity of Approaches To Learning in Universities in Hong Kong and Sydney
Authors: Leung Doris Y.P. , Ginns Paul , Kember David
Published: February 2008

Western research has characterized approaches to learning for specific learning tasks as discrete deep and surface approaches, distinguished by whether the intention is to understand or memorize. A more appropriate classification scheme for Hong Kong research is a continuum between deep and surface poles. In this article, the authors examine whether this characterization applies also to the West. University students in Australia ( n = 1,146) and Hong Kong ( n = 1,266) complete the revised Study Process Questionnaire. There are no effects by either discipline or study level in either country. Multiple-group analyses using structural equation modeling show configural invariance across the two samples, suggesting that the continuum characterization of approaches to learning is likely to be applicable for Western counterparts. Hong Kong students had higher mean scores for both deep and surface approaches, showing their greater use of intermediate approaches.
The Growing Engagement of Emergent Concerned Groups in Political and Economic Life
Authors: Callon Michel , Rabeharisoa Vololona
Published: February 2008

This article discusses the notion of emergent concerned groups and explores how these groups contribute to shaping the relations between technoscience, politics, and economic markets. The first part presents the case of the French Association of patients suffering from muscular dystrophies. This history suggests that under certain conditions, emergent concerned groups are able to impose a new form of articulation between scientific research and political identities by directly linking the issues of research content and results to that of their place in the collective. The second part argues that the evolution of economic markets, combined with that of science and technology, leads to a multiplication of those emergent concerned groups. The study of the conditions under which these emergent groups become legitimate stakeholders as well as the analysis of their impact on market organization and technoscientific institutions are key research topics for the near future.
“Opening Up” and “Closing Down”
Authors: Stirling Andy
Published: February 2008

Discursive deference in the governance of science and technology is rebalancing from expert analysis toward participatory deliberation. Linear, scientistic conceptions of innovation are giving ground to more plural, socially situated understandings. Yet, growing recognition of social agency in technology choice is countered by persistently deterministic notions of technological progress. This article addresses this increasingly stark disjuncture. Distinguishing between “appraisal” and “commitment” in technology choice, it highlights contrasting implications of normative, instrumental, and substantive imperatives in appraisal. Focusing on the role of power, it identifies key commonalities transcending the analysis/participation dichotomy. Each is equally susceptible to instrumental framing for variously weak and strong forms of justification. To address the disjuncture, it is concluded that greater appreciation is required—in both analytic and participatory appraisal—to facilitating the opening up (rather than the closing down) of governance commitments on science and technology.