Search

Introduction Cardiovascular disease--more specifically ischemic heart disease and stroke--accounts for a third of all deaths worldwide (GBD 2013 Mortality and Causes of Death Collaborators 2015); it follows that atherosclerosis is [...], Prediction of coronary events remains elusive. Carotid atherosclerosis may be a surrogate for coronary risk, as carotid and coronary diseases occur simultaneously--albeit at times with a weak association--depending on clinical presentation. We investigated carotid and coronary atherosclerosis in men with new-onset unstable coronary artery disease (CAD) presenting with acute ST-segment elevation myocardial infarction (STEMI) vs. long-standing severe chronic stable angina (CSA). Bilateral carotid artery and 3-vessel coronary artery atherosclerosis burdens were measured within 1 month, respectively, by 3D-volumetric carotid magnetic resonance imaging and coronary angiography-derived modified CASS-50 score. Men with STEMI (n = 50) and long-standing CSA (n = 50), matched for age, were enrolled (58.6 [+ or -] 8.8 years). All of them had carotid atherosclerosis. Atherosclerosis burden was greater in the carotid arteries of STEMI vs. CSA (wall volume: 196.2 [+ or -] 44.4 vs. 169.2 [+ or -] 38.0 [mm.sup.3]/4 mm, p = 0.002), but greater in the coronary arteries of CSA vs. STEMI (modified CASS-50 score: 3 vs. 1, p < 0.0001). Normalized wall index (NWI) of internal carotid was associated with modified CASS-50 score in STEMI ([rho] = 0.40, p = 0.022) and in CSA ([rho] = -0.39, p = 0.031). Carotid atherosclerosis was observed in all CAD patients, and atherosclerosis burden in carotid and in coronary arteries varied according to clinical presentation. Key words: atherosclerosis, carotid and coronary artery disease, magnetic resonance imaging, myocardial infarction, angina. La prediction des evenements coronariens est un objectif qui demeure difficile a atteindre. L&apos;atherosclerose de l&apos;artere carotide pourrait constituer un substitut pour le risque coronarien, car les maladies carotidiennes et les coronaropathies surviennent simultanement--bien que l&apos;association soit parfois tenue--selon la presentation clinique. Nous avons etudie l&apos;atherosclerose carotidienne et coronarienne chez des hommes atteints d&apos;une nouvelle coronaropathie avec presentation d&apos;un infarctus du myocarde aigu avec elevation du segment ST (STEMI pour <>) comparativement a une angine stable chronique (ASC) grave de longue date. Nous avons mesure le fardeau atherosclerotique sur les deux arteres carotides et les trois vaisseaux coronariens a l&apos;interieur d&apos;un mois a l&apos;aide de l&apos;imagerie par resonance magnetique volumetrique tridimensionnelle de la carotide et du score CASS-50 fonde sur la coronarographie, respectivement. Nous avons inscrit a l&apos;etude des hommes atteints de STEMI (n = 50) et d&apos;ASC de longue duree (n = 50) apparies selon l&apos;age (58,6 [+ or -] 8,8 ans). Ils presentaient tous de l&apos;atherosclerose carotidienne. Le fardeau atherosclerotique etait plus eleve dans les arteres carotides du groupe STEMI que dans le groupe ASC (volume de la paroi: 196,2 [+ or -] 44,4 vs 169,2 [+ or -] 38,0 [mm.sup.3]/4 mm, p = 0,002), mais il etait plus eleve dans les arteres coronaires du groupe ASC que dans le groupe STEMI (score CASS-50 modifie : 3 vs 1, p < 0,0001). L&apos;indice normalise de la paroi de la carotide interne etait associe a un score CASS-50 modifie dans le groupe STEMI ([rho] = 0,40, p = 0,022) et dans le groupe ASC ([rho] = -0,39, p = 0,031). Nous avons observe de l&apos;atherosclerose carotidienne chez tous les patients atteints de coronaropathie, et le fardeau de l&apos;atherosclerose dans les arteres carotides et coronaires variait en fonction de la presentation clinique. [Traduit par la Redaction] Mots-cles: atherosclerose, maladie carotidienne et coronaropathie, imagerie par resonance magnetique, infarctus du myocarde, angine.

Introduction Hyperhomocysteinemia is associated with cardiovascular disease (Hoogeveen et al. 2000; Kumakura et al. 2015; McCully 1969; Refsum et al. 1998; Riksen et al. 2003) and a predictor for death [...], The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration (APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7). Seventy-eight patients (mean age ± SD: 66.3 [+ or -] 11.3; mean SYNTAX score: 19.9 ± 12.3) and 30 healthy subjects (mean age: 61 ± 13) were included. We incubated HuH7 cells with increasing concentrations of adenosine and addressed the effect on HCys level in cell culture supernatant. Patients vs. controls had higher APC (0.82 [+ or -] 0.5 µmol/L vs 0.53 ± 0.14 µmol/L; p < 0.01), HCys (15 ± 7.6 µmol/L vs 6.8 ± 3 µmol/L, p < 0.0001), and uric acid (242.6 ± 97 vs 202 ± 59, p < 0.05) levels. APC was correlated with HCys and uric acid concentrations in patients (Pearson's R = 0.65 and 0.52; p < 0.0001, respectively). The SYNTAX score was correlated with HCys concentration. Adenosine induced a time- and dose-dependent increase in HCys in cell culture. Our data suggest that high APC is associated with HCys and uric acid concentrations in CAD patients. Whether the increased APC participates in atherosclerosis or, conversely, is part of a protective regulation process needs further investigations. Key words: adenosine, homocysteine, coronary artery disease. Le role de l'hyperhomocysteinemie dans la coronaropathie n'a toujours pas ete precise. La presente etude vise a evaluer le lien entre les concentrations plasmatiques d'homocysteine (HCys), d'adenosine (CPA), d'acide urique et la gravite de la coronaropathie a l'aide du score SYNTAX. Nous avons aussi evalue in vitro l'influence de l'adenosine sur la production d'HCys par les cellules d'hepatome en culture (HuH7). Nous avons inscrit a l'etude 78 patients (moyenne d'age ± E-T : 66,3 ± 11,3; score SYNTAX moyen: 19,9 ± 12,3) et 30 sujets en bonne sante (moyenne d'age : 61 ± 13). Par ailleurs, nous avons fait incuber des cellules HuH7 en presence d'adenosine a des concentrations croissantes et evalue son effet sur la concentration d'HCys dans le surnageant de culture cellulaire. Les concentrations plasmatiques des elements suivants etaient plus elevees chez les patients que chez les temoins: adenosine (0,82 ± 0,5 µmol/L p/r a 0,53 ± 0,14 µmol/L, p < 0,01), HCys (15 ± 7,6 µmol/L p/r a 6,8 [+ or -] 3 µmol/L, p < 0,0001) et acide urique (242,6 ± 97 p/r a 202 ± 59, p < 0,05). L'augmentation de la CPA etait proportionnelle a celles des concentrations d'HCys et d'acide urique chez les patients (R de Pearson : 0,65 et 0,52, respectivement; p < 0,0001) et l'augmentation du score SYNTAX etait proportionnelle a celle des concentrations d'HCys. En culture cellulaire, nous avons observe une augmentation, dependante du temps et de la dose, des concentrations d'HCys en presence d'adenosine. Nos donnees laissent entendre que la CPA est associee aux concentrations d'HCys et d'acide urique chez les patients presentant une coronaropathie. Par ailleurs, d'autres etudes seraient necessaries pour savoir si la CPA participe a l'atherosclerose ou si, inversement, elle contribue a un processus de protection regulateur. [Traduit par la Redaction] Mots-cles: adenosine, homocysteine, coronaropathie.

Introduction Cardiovascular disease, as reported by The World Health Organization (WHO), is the largest contributor to global mortality and it is supposed to dominate mortality trends in the future (WHO [...], One of many risk factors for cardiovascular disease appears to be oxidative stress. To estimate possible changes in redox balance, membrane fluidity, and cholesterol level in erythrocytes was collected erythrocytes from patients diagnosed with coronary artery disease (CAD). The study included 20 patients with previous myocardial infarction occurring more than 6 months prior to the time of screening with low-density lipoprotein cholesterol (LDL-C) >70 mg/dL and 21 healthy controls. The following parameters were studied: catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD), thiobarbituric acid reactive substrates (TBARS), sulfhydryl (SH) groups in membrane protein, total cholesterol level, and erythrocyte membrane fluidity. Our study showed an increase in the level of lipid peroxidation (13%) and total cholesterol (19%), and a decrease in membrane fluidity (14%) in the subsurface layers and in the deeper layers of erythrocyte membrane (7%) isolated from patients with CAD in comparison to healthy controls. A significant decrease in catalase (10%) and SOD (17%) activities were also observed. No changes in GPx activity or the level of SH groups were observed. Our study indicates that there are disorders in the antioxidant system as well as changes in the membrane structure of erythrocytes obtained from CAD patients. Key words: coronary artery disease, lipid peroxidation, total cholesterol, membranes fluidity, antioxidant system. Le stress oxydant semble constituerun des nombreux facteurs de risque de developper une maladie cardiovasculaire. Nous avons ainsi decide d&apos;evaluer le lien qui existe entre les changements possibles de l&apos;equilibre redox, la fluidite membranaire et le niveau de cholesterol, dans des erythrocytes preleves de patients chez qui l&apos;on a diagnostique une maladie coronarienne (MC). Cette etude impliquait 20 patients ayant presente un infarctus du myocarde au moins 6 mois avant la periode de selection et dont les LDL-C etaient > 70 mg/dl, et 21 sujets sains. Les parametres suivants ont ete etudies: activite des enzymes antioxydantes soit la catalase (CAT), la glutathion peroxydase (GPx), la superoxyde dismutase (SOD), les substrats reactifs a l&apos;acide thiobarbiturique (TBARS), les groupes SH des proteines membranaires, le niveau de cholesterol total et la fluidite membranaire des erythrocytes. Notre etude a revele un accroissement de la peroxydation lipidique (13 %) et du cholesterol total (19 %), et une diminution de la fluidite membranaire (14 %) dans les couches sous la surface et de 7 % dans les couches plus profondes de la membrane des erythrocytes isoles de patients avec MC comparativement au groupe sain. Une diminution significative de l&apos;activite de la CAT (10 %) et de la SOD (17 %) a aussi ete observee. Aucun changement d&apos;activite de la GSH-Px ou de niveau de groupes SH n&apos;a ete note. Notre etude a mis en evidence des perturbations du systeme antioxydant ainsi que des changements de la structure de la membrane des erythrocytes preleves de patients ayant re^u un diagnostic de MC. [Traduit par la Redaction] Mots-cles: maladie coronarienne, peroxydation lipidique, cholesterol total, fluidite membranaire, systeme antioxidant.

Atherosclerosis is an inflammatory process leading to enhanced cellular proliferation, apoptosis, and vasa vasorum (VV) neovascularization. While both diabetes mellitus (DM) and hypercholesterolemia (HC) predispose to atherosclerosis, the precise interaction of these risk factors is unclear. Akt is a central node in signaling pathways important for inflammation, and we hypothesized that DM/HC would lead to aberrant Akt signaling and advanced, complex atherosclerosis. DM was induced in pigs by streptozotocin and HC by a high-fat diet. Animals were randomized to control (non-DM, non-HC), DM only, HC only, and DM/HC groups. Coronary artery homogenates were analyzed by immunoblotting for proteins involved in the Akt pathway, including phosphorylated (p)-Akt (Ser473), p-GSK-3[beta] (Set9), activated NF-[kappa]B p65, and VEGF. Immunohistochemical staining for Ki67 (cell proliferation), terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) (apoptosis), and von Willebrand factor (vWF) (neovascularization) was performed. Neovascularization was visualized with micro-computerized tomography (CT). Only DM/HC animals developed advanced atherosclerosis and showed decreased p-Akt (Ser4731 and p-GSK-3[beta] (Ser9) levels (P < 0.01 and P < 0.05, respectively). DM/HC arteries demonstrated increased cellular proliferation (P < 0.001), apoptosis (P < 0.01), and activation of NF-[kappa]B p65 (P < 0.05). Induction of DM/HC also resulted in significant VV neovascularization by enhanced VEGF expression (P < 0.05), increased vWF staining (P < 0.011, and increased density by micro-CT. In conclusion, DM and HC synergistically resulted in complex atherosclerosis associated with attenuated p-Akt (Ser473) levels. Aberrant Akt signaling correlated with increased inflammation, cellular proliferation, apoptosis, and VV neovascularization. Our results revealed a synergistic effect of DM and HC in triggering abnormal Akt signaling, resulting in advanced atherosclerosis. atherosclerosis; vasa vasorum neovascularization; vascular endothelial growth factor; glycogen synthetase kinase-3[beta]; nuclear factor-[kappa]B; Akt doi: 10.1152/ajpheart.00071.2010.

Several experimental studies are conducted to explain the genetic determinants that are associated with the Lp(a) lipoprotein level and the coronary disease in patients. The Lp(a) lipoprotein is shown to exhibit a significant role in the onset of the coronary disease.

A newly devised, high-sensitive assay is employed to determine the distribution, as well as the association of the cardiac troponin T levels with the various cardiovascular events. The analysis proves that the troponin T levels are highly associated with the coronary artery disease and often leads to cardiovascular death and heart failure.

Erectile dysfunction frequently coexists with coronary artery disease and has been proposed as a potential marker for silent coronary artery disease in type 2 diabetes. In the present study, we comparatively assessed the structural and functional changes of both penile arteries (PAs) and coronary arteries (CAs) from a prediabetic animal model. PAs and CAs from 17- to 18-wk-old obese Zucker rats (OZRs) and from their control counterparts [lean Zucker rats (LZRs)] were mounted in microvascular myographs to evaluate vascular function, and stained arteries were subjected to morphometric analysis. Endothelial nitric oxide (NO) synthase (eNOS) protein expression was also assessed. The internal diameter was reduced and the wall-to-lumen ratio was increased in PAs from OZRs, but structure was preserved in CAs. ACh-elicited relaxations were severely impaired in PAs but not in CAs from OZRs, although eNOS expression was unaltered. Contractions to norepinephrine and 5-HT were significantly enhanced in both PAs and CAs, respectively, from OZRs. Blockade of NOS abolished endothelium-dependent relaxations in PAs and CAs and potentiated norepinephrine and 5-HT contractions in arteries from LZRs but not from OZRs. The vasodilator response to the phosphodiesterase 5 inhibitor sildenafil was reduced in both PAs and CAs from OZRs. Pretreatment with SOD reduced the enhanced vasoconstriction in both PAs and CAs from OZRs but did not restore ACh-induced relaxations in PAs. In conclusion, the present results demonstrate vascular inward remodeling in PAs and a differential impairment of endothelial relaxant responses in PAs and CAs from insulin-resistant OZRs. Enhanced superoxide production and reduced basal NO activity seem to underlie the augmented vasoconstriction in both PAs and CAs. The severity of the structural and functional abnormalities in PAs might anticipate the vascular dysfunction of the more preserved coronary vascular bed. vascular remodeling; endothelial dysfunction; coronary artery; penile artery; erectile dysfunction

Statins have been shown to be cardioprotective; however, their interaction with endogenous cardioprotection by ischemic preconditioning and postconditioning is not known. In the present study, we examined if acute and chronic administration of the 3-hydroxy-3-methylglutaryl CoA reductase inhibitor lovastatin affected the infarct size-limiting effect of ischemic preconditioning and postconditioning in rat hearts. Wistar rats were randomly assigned to the following three groups: 1) vehicle (1% methylcellulose per os for 12 days), 2) chronic lovastatin (15 mg.[kg.sup.-1].[day.sup.-1] per os for 12 days), and 3) acute lovastatin (1% methylcellulose per os for 12 days and 50 [micro]mol/1 lovastatin in the perfusate). Hearts isolated from the three groups were either subjected to a nonconditioning (aerobic perfusion followed by 30-min coronary occlusion and 120-min reperfusion, i.e., test ischemia-reperfusion), preconditioning (three intermittent periods of 5-min ischemia-reperfusion cycles before test ischemia-reperfusion), or postconditioning (six cycles of 10-s ischemia-reperfusion after test ischemia) perfusion protocol. Preconditioning and postconditioning significantly decreased infarct size in vehicle-treated hearts. However, preconditioning failed to decrease infarct size in acute lovastatin-treated hearts, but the effect of postconditioning remained unchanged. Chronic lovastatin treatment abolished postconditioning but not preconditioning; however, it decreased infarct size in the nonconditioned group. Myocardial levels of coenzyme Q9 were decreased in both acute and chronic lovastatin-treated rats. Western blot analysis revealed that both acute and chronic lovastatin treatment attenuated the phoshorylation of Akt; however, acute but not chronic lovastatin treatment increased the phosphorylation of p42 MAPK/ERK. We conclude that, although lovastatin may lead to cardioprotection, it interferes with the mechanisms of cardiac adaptation to ischemic stress. coronary occlusion; coenzyme Q9; Akt; p42 mitogen-activated protein kinase/extracellular signal-regulated kinase; statin

Recently, it has been questioned whether elevated levels of circulating plant sterols increase the risk of coronary heart disease (CHD). To date, no definitive conclusions regarding such a relationship have been reached, nor have there been any studies summarizing the factors that contribute to the observed elevations in plant sterol concentrations in plasma. Thus, the purpose of this review is to systematically compare the plant sterol levels of subjects from the general population and to describe factors that contribute to the variations observed. The question of whether elevated plasma concentrations of plant sterols are associated with an increased risk of CHD was also assessed. Results indicate that the key factors accounting for variations in circulating plant sterol concentrations include: apolipoprotein E phenotypes, ATP-binding cassette transporter polymorphisms, use of statin drugs, presence of metabolic syndrome, dietary intake of plant sterols, gender, and analytical techniques used in the measurement of plant sterols in the plasma. An analysis of the studies examining the relationship between circulating levels of plant sterols and CHD risk in non-sitosterolemic populations revealed no clear associations. Furthermore, it was shown that the above-mentioned factors play an important role in determining the levels of plant sterols in plasma. Since these factors may act as potential confounders, they must be controlled for before more solid conclusions can be reached. Key words: blood concentrations, coronary heart disease, cholesterol, plant sterols doi: 10.1301/nr.2006.sept.385-402

Hyperglycemia is associated with generation of reactive oxygen species (ROS), and this action may contribute to accelerated atherogenesis. We tested the hypothesis that hyperglycemia produces alterations in left anterior descendlng coronary artery (LAD) wall shear stress concomitant with endothelial dysfunction and ROS production in dogs (n = 12) instrumented for measurement of LAD blood flow, velocity, and diameter. Dogs were randomly assigned to receive vehicle (0.9% saline) or the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempo]) and were administered intravenous infusions of v-glucose to achieve target blood glucose concentrations of 350 and 600 mg/dl (moderate and severe hyperglycemia, respectively). Endothelial function and ROS generation were assessed by coronary blood flow responses to acetylcholine (10, 30, and 100 ng/kg) and dihydroethidium fluorescence of myocardial biopsies, respectively. Indexes of wall shear stress were calculated with conventional fluid dynamics theory. Hyperglycemia produced dose-related endothelial dysfunction, increases in ROS production, and reductions in oscillatory shear stress that were normalized by tempo]. The results suggest a direct association between hyperglycemia-induced ROS production, endothelial dysfunction, and decreases in oscillatory shear stress in vivo. coronary artery disease; diabetes; oscillatory shear stress; oxidant stress