Mechanisms related atherosclerosis

Stroke mechanisms related to large artery atherosclerosis... 

Del Boccio, C., Laprenna, D., Porreca, E., Pennilli, A., Savini, F., Feliciani, P., Ricci, G. and CuccuruUo, F. (1990). Aortic antioxidant defence mechanisms time-related changes in cholesterol fed rabbits. Atherosclerosis 81, 127-135. 

This review reports the more recent evidence for the ability of P-carotene and other carotenoids to modulate cell signaling related to cell growth and implicated in a lot of pathological events, including cancer, inflammation, and atherosclerosis by both redox and non-redox mechanisms. 

The ACE gene encodes two isozymes (somatic ACE isozyme and germinal ACE isozyme). ACE is a membrane-bound enzyme on the surface of vascular endothelial cells that also circulates in plasma and shows great individual variability determined by an I/D polymorphism in intron 16 of the ACE gene (ACE-I/D polymorphism). More than 160 ACE polymorphisms have been reported, 34 of which are located in coding regions, and 18 are missense mutations (606). ACE-related polymorphic variants have been associated with hypertension, atherosclerosis, stroke, left ventricular hypertrophy, chronic renal failure in IgA nephropathy, Henoch-Schonlein purpura nephritis, mechanical efficiency of skeletal muscle, intracranial aneurysms, susceptibility to myocardial infarction, diabetic nephropathy, AD, and longevity (12,606,607). 

Body iron level and iron depletion play an important role in the gender differences seen in death from cardiac disease. There is a better correlation with heart disease mortality in iron levels compared with levels of cholesterol (5). It was found that risk of coronary heart disease (6) and carotid atherosclerosis (7) is associated with increased iron stores. However, impaired endothelium-derived nitric oxide activity may be without overt atherosclerosis in patients with risk factors and may be associated with the presence of atherosclerosis (4). Thus, endothelial dysfunction related to iron activity not only may be an early marker for cardiovascular risk but also may contribute to the pathogenesis of atherosclerosis (2) by the stimulation of low-density lipoproteins (LDL) and membrane lipid peroxidation (I) and may be a key to the understanding of early mechanism in the development of atheroma (7,8). Nakayama et al. (9) showed the role of heme oxygenase induction in the modulation of macrophage activation in atherosclerosis. However, Howes et al. (10) concludes that at the moment, the available evidence on iron hypothesis remains circumstantial. Moreover, Kiechl et al. (7) showed that the adverse effect of iron is hypercholesterolemia, In patients... 

Chest pain in the absence of CAD is a common symptom of patients with HCM. However, it is appropriate to consider typical CAD in any patient with HCM if they have the usual risk factors for atherosclerosis. There are several mechanisms proposed for the myocardial ischemia seen in this patient population. There may be inadequate capillary density in relation to the increased LV muscle mass. The small intramural coronary arteries may be abnormally narrowed... 

In this concluding section we examine the relation between lipid metabolism and atherosclerosis, the most common cause of heart attacks and strokes. Atherosclerosis accounts for 75 percent of deaths due to cardiovascular disease in the United States. Advances in our understanding of the molecular mechanisms underlying lipid metabolism and its regulation are having an enormous effect on the treatment and prevention of this major health problem. 

Other effects. There are many, some probably still unknown. However, effects on the kidneys, bladder, atherosclerosis, hemodynamic and hemostatic mechanisms, the skeletal system, association of malignancies with PG-induced hypercalcemia, other malignancy-related metabolic processes, and even glucose metabolism are being investigated. 

Pre-menopausal women suffer less cardiovascular disease than men do. This protection disappears, however, after the menopause, and hormone replacement therapy in post-menopausal women reduces cardiovascular mortality. Animal work suggests that oestrogens dilate blood vessels by an endothelium-dependent mechanism, but as yet there is no direct evidence to show that NO generation is different between men and women. This is an area of considerable interest, particularly as women have greater longevity than men and suffer less ischaemic heart disease. Abnormal NO production may occur in hypercholesterolaemia and may be related to subsequent development of atherosclerosis. There is now a body of experimental data to suggest that an abnormality in NO production or function may be causal, or at least an amplifying factor, in both hypercholesterolaemia and atherosclerosis. 

Background It is well known that hypercholesterolemia is a major risk factor in the progression of atherosclerosis, the major cause of cardiovascular diseases. Statins are widely used to treat hypercholesterolemia. The mechanism of action of these drugs is to reduce the endogenous production of cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase. Atorvastatin (ATV, Lipitor) is one of the top-selling prescribed oral medications. The only known adverse effect is skeletal muscle toxicity (myopathy) that may be related to the formation of the lactone of the acidic side chain on the molecule. 

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