Effects of purpurogallin (PPG), an antioxidant on high cholesterol diet-induced atherosclerosis, and changes in blood lipid profile and lipid peroxidation product malondialdehyde (MDA), aortic tissue MDA, chemiluminescence (M-CL), a marker for antioxidant reserve and antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)] were investigated in rabbits. The rabbits were divided into three groups: Group I, regular rabbit chow; Group II, same as Group I+cholesterol (1%); and Group III, same as Group II+PPG (14 mg/kg, orally, daily). Serum concentrations of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and blood MDA were measured before and after 4 and 10 weeks on the respective diets. The aorta was removed at the end of 10 weeks for assessment of atherosclerotic changes, MDA concentration, M-CL, and antioxidant enzymes. Coronary arteries were also examined for atherosclerotic changes. Serum TC, LDL-C, and LDL-C/HDL-C ratio increased whereas HDL-C decreased in Group II and their values were similar in Groups II and III. Aortic tissue MDA, M-CL, CAT, and GSH-Px activity increased in Group II but these values in Group III were lower than in Group II except for MDA which was greater in Group III than in Group II. Atherosclerotic changes were greater in Group II than in Group III. Histological changes were similar in Groups II and III. Atherosclerotic changes were also observed in the coronary arteries of Groups II and III, however, they were less in Group III than in Group II. Increased levels of aortic MDA and decreased levels of antioxidant reserve, which were associated with the development of atherosclerosis, suggest a role for oxygen radicals in the pathogenesis of hypercholesterolemic atherosclerosis. The protection afforded by PPG, which was associated with reversal of the antioxidant reserve to control level, in spite of hypercholesterolemia, supports the hypothesis that oxygen radicals are involved in the development of hypercholesterolemic atherosclerosis. These results suggest that PPG retard the development of hypercholesterolemic atherosclerosis because of its antioxidant activity without lowering blood cholesterol level.
Abstract Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Ischemic stroke and heart disease, coronary heart disease, and cardiovascular disease are events resulting from long-lasting and silent atherosclerosis. This paper deals with the synthesis of homocysteine (Hcy), causes of HHcy, mechanism of HHcy-induced atherosclerosis, and treatment of HHcy. Synthesis and metabolism of Hcy involves demethylation, transmethylation, and transsulfuration, and these processes require vitamin B6 and vitamin B12 folic acid (vitamin B9). Causes of HHcy include deficiency of vitamins B6, B9, and B12, genetic defects, use of smokeless tobacco, cigarette smoking, alcohol consumption, diabetes, rheumatoid arthritis, low thyroid hormone, consumption of caffeine, folic acid antagonist, cholesterol-lowering drugs (niacin), folic acid antagonist (phenytoin), prolonged use of proton pump inhibitors, metformin, and hypertension. HHcy-induced atherosclerosis may be mediated through oxidative stress, decreased availability of nitric oxide (NO), increased expression of monocyte chemoattractant protein-1, smooth muscle cell proliferation, increased thrombogenicity, and induction of arterial connective tissue. HHcy increases the generation of atherogenic biomolecules such as nuclear factor-kappa B, proinflammatory cytokines (IL-1β, IL-6, and IL-8), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selection), growth factors (IGF-1 and TGF-β), and monocyte colony-stimulating factor which lead to the development of atherosclerosis. NO which is protective against the development of atherosclerosis is reduced by HHcy. Therapy with folic acid, vitamin B6, and vitamin B12 lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B6, vitamin B12, omega-3 fatty acid, and green coffee extract reduce Hcy. Abstaining from drinking coffee and alcohol, and smoking also reduces blood levels of Hcy. In conclusion, HHcy induces atherosclerosis by generating atherogenic biomolecules, and treatment of atherosclerosis-induced diseases may be by reducing the levels of Hcy.
Many of us are still unfamiliar with the man who is behind the successful story of the International Journal of Angiology (IJA), the official journal of the International College of Angiology, and an official publication of the International College of Surgeons, and Asian Society for Vascular Surgery. There is much cause for celebration of this success. This journal was started some 20 years ago by Professor John B. Chang. Under the leadership of Prof. Chang, Founder and Editor-in-Chief, IJA is progressing and flourishing very well. Prof. Chang has been a partner, leader, founder, and funder. There is so much credit due for Prof. Chang's worthwhile endeavor.
The effects of glucagon (5, 10, and 40 mug/ml) on the amplitude and dueation of action potential, effective refractory period, dv/dt of phase 0 of action potential, membrane responsiveness, and contraction in human papillary muscles obtained from patients undergoing corrective open heart surgery were investigated. Glucagon, in none of the concentrations, produced any significant change in the amplitude and dueation of action potential, or in force of contraction. Shortening of the effective refractory period was not significant. Glucagon enhanced the conduction and the membrane responsiveness by increasing the dv/dt of phase 0 of action potential and a shift of curve to the left. It is suggested that the latter properties of glucagon would abolish the "re-entrant" type of cardiac arrhythmias produced by cardiac glycosides or other drugs that initiate and perpetuate arrhythmias dur to altered conduction.
Secoisolariciresinol diglucoside (SDG), a lignan isolated from flaxseed, is a phytoestrogen. Estrogens and phytoestrogen from soy have been reported to have mild hypotensive effects. Effects of SDG on arterial pressures are not known. The objective of this study was to determine whether (a) SDG has a hypotensive effect, and (b) the hypotensive effect is mediated through the L-arginine-nitric oxide pathway. The studies were conducted in anesthetized Sprague Dawley normotensive rats weighing between 450 and 500 grams Carotid arterial pressures were recorded to investigate the changes in the arterial pressures and heart rate with various doses of SDG. Maximum drops in the mean arterial pressure, which occurred at 15 minutes after intravenous SDG, were 40%, 41%, and 47%, respectively, with 10 mg, 15 mg, and 20 mg/kg of SDG. The pressures tended to recover, but even at the end of four hours, the percent drops in the mean arterial pressures were 33, 22, and 29, respectively, with 10 mg, 15 mg, and 20 mg/kg of SDG. The drops in the diastolic and mean arterial pressures were slightly higher than systolic pressures. Smaller doses of SDG (3 and 5 mg/kg) produced dose-dependent decreases in the systolic, diastolic, and mean arterial pressures. Heart rate remained unchanged. Pretreatment with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, did not prevent the SDG-induced reduction in arterial pressures. However, pretreatment with methylene blue (MB), a nonspecific, and oxadiazolo quinoxalin (ODQ), a specific inhibitor of guanylate cyclase, completely prevented the SDG-induced reduction in the arterial pressures. These results suggest that SDG is a long-acting hypotensive agent, and that the hypotensive effect is mediated through the guanylate cyclase enzyme.
The interaction of advanced glycation end products (AGEs) with its cell-bound receptor RAGE increases gene expression and release of proinflammatory cytokines and increase generation of reactive oxygen species (ROS). Circulating receptors, soluble RAGE (sRAGE), and endosecretory RAGE (esRAGE) by binding with RAGE ligands have protective effects against AGE–RAGE interaction. Cigarette smoking is a risk factor for coronary artery disease, stroke, and peripheral vascular disease. This article reviews; if the AGE–RAGE axis is involved in the cigarette smoke-induced cardiovascular diseases. There are various sources of AGEs in smokers including, gas/tar of cigarette, activation of macrophages and polymorphonuclear leukocytes, uncoupling of endothelial isoform of nitric oxide synthase (eNOS) and xanthine oxidase. The levels of AGEs are elevated in smokers. Serum levels of sRAGE have been reported to be reduced, elevated, or unchanged in smokers. Mostly the levels are reduced. There is one article which shows an elevation of levels of sRAGE in smokers. Serum levels of esRAGE are unaltered in smokers. Mechanism of AGE–RAGE-induced atherosclerosis has been discussed. Atherosclerosis leads to the cardiovascular diseases. It has been suggested that ratio of AGE/sRAGE or AGE/esRAGE is useful in determining the deleterious effects of AGE–RAGE interaction in smokers. sRAGE alone is not a good marker for smoke-induced cardiovascular disease. In conclusion cigarette smoke induces formation of AGEs and reduces sRAGE resulting in the development of atherosclerosis and related coronary heart disease, stroke, and peripheral vascular disease. Ratio of AGEs/sRAGE is a better marker for cardiovascular disease than AGEs or sRAGE alone in smokers.
We investigated the effects of superoxide anions (O2−) generated by xanthine (X) plus xanthine oxidase (XO) on isolated rabbit aorta suspended in Krebs-Ringer solution. Xanthine plus xanthine oxidase produced concentration-dependent contractions of rabbit aorta. Superoxide dismutase completely reversed the contractile response observed. Superoxide anion-induced contraction of rabbit aorta was totally abolished in preparations denuded of endothelium. The contractile effect was reduced by 56% by the cyclooxygenase inhibitor, indomethacin. The contractile effect was not affected by the angiotensin converting enzyme inhibitor, captopril. These results indicate that O2 − produces a contraction of the isolated rabbit aorta that is endothelium-dependent and is partly mediated by an arachidonic acid metabolite.
