Arya Atherosclerosis
Volume:3 Issue: 2, Summer 2007

Increased serum level of vascular endothelial growth factor (VEGF) iswell-documented in hypercholesterolemia and atherosclerosis. It is associated withatherosclerotic lesions and is considered as a marker for endothelial dysfunction andinjury. In the present study, experiments were designed to examine the combined effectsof dietary lipid withdrawal and L-arginine supplementation on serum VEGF concentration. After 4 weeks on a high-cholesterol diet, white male rabbits (n=22) wererandomly assigned to 2 groups. The diet withdrawal (DW) group (n=11) was fed normaldiet and the L-arginine group was fed normal diet and 3% L-arginine in drinking waterfor another 4 weeks. The serum levels of lipids, VEGF and L-arginine were measuredbefore and after 4 and 8 weeks of experiment. The cholesterol-rich diet induced a significant increase in total cholesteroland LDL-cholesterol in all animals. There was no significant difference between thegroups (P>0.05). After 4 weeks of cholesterol-rich diet withdrawal, animals of the DWand the L-arginine group had similar levels of total cholesterol and LDL-cholesterol. Larginine supplementation resulted in a significantly higher serum level of L arginine inthe L-arginine group than in the DW group (P<0.05). After 4 weeks, no significantdifference was found between the serum level of VEGF of the two groups. By the end ofstudy, hypercholesterolemic diet withdrawal had apparently led to decreases in VEGF inboth groups, but the serum level of VEGF was significantly lower in the group treatedwith L-arginine (P<0.05). This study showed the synergistic effect of two endothelial protectivefactors, lipid lowering by diet withdrawal and L-arginine supplementation, on VEGFproduction.

The objective of this study was to evaluate the effect of L-arginine (L Arg) and L-NAME on coronary vascular and aortic endothelial permeability in normocholesterolemic (NC) and hypercholesterolemic (HC) rats. Forty-eight male rats were divided into NC and HC groups and each group was divided into L-Arginine-treated, L-NAME-treated and control subgroups. L-Arg (2.25%) and LNAME (0.75 mg/ml) were dissolved in drinking water and control groups received tap water.After 8 weeks, endothelial permeability was assessed by using the Evans Blue (EB) dye method. Aortic endothelial permeability was significantly higher in HC group compared toNC group (15.1±0.7 vs. 7.7±0.8 μgEB/g tissue, respectively; P<0.05). L-Arg and L-NAME treatment decreased aortic endothelial permeability in HC animals (L-Arg: 8.4±0.4 & L-NAME: 10.8±0.6 vs. 15.1±0.7 μgEB/g tissue, respectively; P<0.05). There was no significant difference in endothelial permeability in coronary circulation between HC and NC groups and L-Arg and L-NAME did not alter endothelial permeability. It seems that L-Arg and L-NAME have different effects on endothelial permeability based on physiological and pathological conditions and type of vessel.

The incidence of atherosclerosis increases with age, as do variousindices of free-radical-mediated damage, e.g. lipid peroxidation. Because Antioxidantenzymes are the major defense system of cells in normal aerobic reactions, we aimed toassess the age-related alterations in the activity of erythrocyte cytoprotective enzymesamong women. One hundred sixty 20-45-year-old women were randomly selected amongwomen receiving the services of rural health centers of Kerman Province, Iran. Data weregathered by using questionnaires and face-to-face interviews. We assessed lipidperoxidation by measuring the concentrations of plasma malondialdehyde (MDA), totalantioxidant capacity (TAC), and the activities of erythrocyte copper-zinc superoxidedismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT). Those individuals in the highest quartiles of age and number of pregnanciespresented the highest levels of plasma MDA (P<0.001). We also observed an inverserelationship between age and erythrocyte CuZn-SOD and GPX activities. Although wefound no significant difference between age groups in respect of erythrocyte CAT activityand/or plasma TAC levels, erythrocyte GPX activity was negatively correlated with thenumber of pregnancies (P<0.001). No significant difference was found between agegroups and/or between quartiles of number of pregnancies for either energy or nutrientintake. Plasma MDA levels were positively related to age (r=0.307; P<0.0001), number ofpregnancies (r=0.250; P<0.001), fat intake (r=0.281; P<0.05) and Vitamin E intake(r=0.356; P<0.01). Furthermore, there were negative correlations both between age and GPX activity (r= -0.280; P<0.0001) as well as with CuZn-SOD(r= -0.228; P<0.005). Lipid peroxidation and antioxidants were affected by age. Erythrocyte cytoprotective enzymes have an important role in detoxification of free radicals in the body; the age-related decrease in the activities of these enzymes might contribute to atherogenesis, along with classic risk factors.

The relationship between ω -3 fatty acids and surrogate circulatingmarkers of cardiovascular disease (CVD) risk, especially in healthy individuals remains tobe determined. We investigated the effects of Eicosapentaenoic acid (EPA)supplementation, with or without vitamin E, on serum lipid profile, C-reactive protein(CRP), blood pressure (BP) and total antioxidant capacity in a sample of male athletes. This randomized double blind placebo-controlled clinical trial wasconducted in 2006 on 34 apparently healthy, well-trained male basketball players, aged17-35 years,. Venous blood samples were obtained between 5:00 and 6:00 p.m., afterexercising for 2 hours, at the baseline and after intervention. Participants received 2 gEPA and/or 400 IU vitamin E and/or placebo depending on their groups. For 6 weeks,eight subjects received an EPA supplement with vitamin E (group 1), nine subjectsreceived an EPA supplement with vitamin E placebo (group 2), nine subjects received anEPA supplement placebo and vitamin E (group 3), and eight subjects received an EPAsupplement placebo and vitamin E placebo (group 4). Significant decreases were documented in the serum levels of totalcholesterol (TC), triglycerides (TG), LDL-C and CRP in group1 (p<0.01), in TC, TG, LDLC,CRP, and BP in group 2 (p<0.01), and significant increase in total antioxidant capacityin group 3 (P<0.05). No significant difference was found in LDL between groups 1 and 4(P<0.05), and in total antioxidant capacity between groups 2 and 3 (p<0.001) and groups 3 and 4 (p<0.001), and in CRP level between groups 2 and 3 (P<0.05). There were no significant differences in TC, TG, HDL-C and BP between the groups after 6 weeks of intervention. Six weeks of EPA+ vitamin E supplementation improved the lipidprofile and reduced the CRP level, whereas six weeks of EPA supplementation withoutvitamin E improved the lipid profile, but increased CRP and BP. Six weeks of vitamin Esupplementation alone increased total plasma antioxidant capacity.

Recent studies indicate that endothelin-1 (ET-1) and abnormality inthe transfer of calcium ions have a role in the atherosclerosis process. Amlodipine caninfluence the risk factors associated with atherosclerosis, but the possible protectivemechanisms of ET-1 are not known. We evaluated the effects of amlodipine and/or highcholesterol diet on blood and renal tissue concentration of endothelin, as well as the role of ET-1 in the pathophysiology of atherosclerosis in male New Zealand white rabbits. Thirty-six male New Zealand white rabbits were divided into four groups:The normal control group, normal group receiving amlodipine, high-cholesterol dietgroup and high-cholesterol diet plus amlodipine group. After 8 weeks, all animals wereanesthetized and blood or tissues samples were colleted. Amlodipine led to significant increase in plasma high-density lipoproteincholesterol (HDL-C) and decrease in serum triglyceride (TG) in the control group. Theplasma level of ET-1 in the atherosclerotic model group increased significantly comparedwith the control group (p<0.01). After 8 weeks of treatment with amlodipine, ET-1 levelsdecreased significantly in the control group (p<0.01) and high-cholesterol diet rabbits(p<0.01). Amlodipine administration significantly reduced the tissue levels of endothelinonly in high-cholesterol diet rabbits (p<0.01). Eight weeks of high-cholesterol diet (2%)did not induce any atherosclerotic lesion in this artery, and amlodipine had no significanteffect. The increase of lipids and ET-1 in the renal artery and plasma with ahigh-cholesterol diet is not linked to the early stages of atherosclerotic plaque formation.Amlodipine can reduce levels of ET-1 and lipids, but the mechanisms remain to bedetermined.

Deviation from normal body size, particularly extreme obesity isassociated with increased postoperative morbidity and mortality. Obesity is oftenperceived to be a risk factor for adverse outcomes following coronary artery surgerybypass graft. The aim of this study was to evaluate the effect of body mass index on theearly outcomes in patients undergoing coronary artery bypass graft (CABG). In a retrospective study, 772 patients undergoing CABG between 2005 and2006 were evaluated in shiraz university affiliated medical centers. The patients’ bodymass index (BMI) was measured and classified as underweight, normal-weight, obeseand severely obese. The clinical data were evaluated with respect to early postoperativeoutcomes and mortality. The main early outcomes were postoperative myocardialinfarction, sternal wound infection, respiratory and renal problems, atrial arrhythmia,bleeding, longer duration of mechanical ventilation, prolonged hospital stay, andincreased operative mortality. The data were gathered using a demographic informationform and a checklist to determine the number of main early outcomes. The forms werecompleted with data from the patients and their records. The effect of BMI on the earlyoutcomes in patients undergoing coronary artery bypass graft (CABG) was assessed usingodds ratio and the logistic regression model. The results showed that of 772 patients, 13.6%, 2.6%, 75.4%, and 8.4% were obese, severely obese, normal-weight, and underweight, respectively.. Obesity and severe obesity increased the risk of sternal wound infection (odds ratio=9.761, P<0.001 and odds ratio=34.441, P<0.001, respectively). Obesity increased the risk of atrial arrhythmia (odds ratio=5.173, P<0.001). Obesity and severe obesity were significantly associated with respiratory problems and postoperative stay longer than 14 days. Severe obesity increased the risk of operative mortality (odds ratio=15.390, P<0.001). There was no difference between obese and severely obese patients in respect of the incidence of myocardial infarction, renal failure, and bleeding following operation. Obesity and severe obesity are associated with increased earlycomplications and operative mortality after CABG, and the degree of obesity plays a keyrole in adverse outcomes of this procedure.. Hence, weight loss can contribute toreduction of postoperative CABG complications and mortality.

Recent studies indicate that endothelin-1 (ET-1) and abnormality inthe transfer of calcium ions have a role in the atherosclerosis process. Amlodipine caninfluence the risk factors associated with atherosclerosis, but the possible protectivemechanisms of ET-1 are not known. We evaluated the effects of amlodipine and/or highcholesterol diet on blood and renal tissue concentration of endothelin, as well as the role of ET-1 in the pathophysiology of atherosclerosis in male New Zealand white rabbits. Thirty-six male New Zealand white rabbits were divided into four groups:The normal control group, normal group receiving amlodipine, high-cholesterol dietgroup and high-cholesterol diet plus amlodipine group. After 8 weeks, all animals wereanesthetized and blood or tissues samples were colleted. Amlodipine led to significant increase in plasma high-density lipoproteincholesterol (HDL-C) and decrease in serum triglyceride (TG) in the control group. Theplasma level of ET-1 in the atherosclerotic model group increased significantly comparedwith the control group (p<0.01). After 8 weeks of treatment with amlodipine, ET-1 levelsdecreased significantly in the control group (p<0.01) and high-cholesterol diet rabbits(p<0.01). Amlodipine administration significantly reduced the tissue levels of endothelinonly in high-cholesterol diet rabbits (p<0.01). Eight weeks of high-cholesterol diet (2%)did not induce any atherosclerotic lesion in this artery, and amlodipine had no significanteffect. The increase of lipids and ET-1 in the renal artery and plasma with ahigh-cholesterol diet is not linked to the early stages of atherosclerotic plaque formation.Amlodipine can reduce levels of ET-1 and lipids, but the mechanisms remain to bedetermined.

A 70-year-old woman with hypertension presented to our clinic for evaluation of chestpain. A very rare anomaly, in which the right coronary artery originated from the leftanterior descending artery, was incidentally found on coronary angiography. The acuteangle made by the anomalous right coronary artery may have reduced the flow velocityand led to signs of myocardial ischemia.