Atherosclerosis pathophysiology

Singh, U., and I. Jialal. 2006. Oxidative stress and atherosclerosis. Pathophysiology 13 129-142. 

Atherogenesis is the process that leads to changes in the arterial blood vessels, including deposition of cholesterol (atherosclerosis). It is the pathophysiological process behind the vast majority of heart attacks. 

Chemokines have been shown to be associated with a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, atherosclerosis, dermatitis, and organ transplant rejection. Evidence, reviewed below, is mounting that chemokines may play a major role in the pathophysiology of these diseases and thus chemokine receptor antagonists could prove to be useful therapeutics in treating these and other proinflammatory diseases. 

Because lipoprotein metabolism and the pathophysiology of atherosclerosis are closely linked, treatment of dyslipidemias is critical for both primary and secondary prevention of IHD-related cardiac events. In 2001, the Adult Treatment Panel III of the National Cholesterol Education Program... 

Atherosclerosis (AS) is a progressive disease characterized by the accumulation of lipids and the development of fibrosis in arterial walls. It is the pathophysiologic process behind cardiovascular disease whose clinical... 

Thus, inflammatory factors play a role at all stages of atherosclerosis in its initiation, progression, and final clinical manifestations. This new understanding of the pathophysiology of atherosclerosis has partly resulted from the study of chemokines and their receptors (4). 

It should also be mentioned that superoxide and not nitric oxide production by eNOS may have implications for atherosclerosis and septic shock due to imbalance between NO and superoxide formation, for example due to an increase in TNF-a production [164]. These pathophysiological functions of NO synthases will be considered in detail in Chapter 31. 

The expression of 15-LOX in atherosclerotic lesions is one of the major causes of LDL oxidative modification during atherosclerosis. To obtain the experimental evidence of a principal role of 15-LOX in atherosclerosis under in vivo conditions, Kuhn et al. [67] studied the structure of oxidized LDL isolated from the aorta of rabbits fed with a cholesterol-rich diet. It was found that specific LOX products were present in early atherosclerotic lesions. On the later stages of atherosclerosis the content of these products diminished while the amount of products originating from nonenzymatic lipid peroxidation increased. It was concluded that arachidonate 15-LOX is of pathophysiological importance at the early stages of atherosclerosis. Folcik et al. [68] demonstrated that 15-LOX contributed to the oxidation of LDL in human atherosclerotic plaques because they observed an increase in the stereospecificity of oxidation in oxidized products. Arachidonate 15-LOX is apparently more active in young human lesions and therefore, may be of pathophysiological importance for earlier atherosclerosis. In advanced human plaques nonenzymatic lipid peroxidation products prevailed [69],... 

Patients with both type 1 and type 2 diabetes are prone to complications. The specific chronic diabetic complications are due to microangiopathy and include neuropathy, retinopathy and nephropathy. Recent data stress the vital role of hyperglycaemia and oxidative stress in their pathophysiology. Premature atherosclerosis (which can be considered... 

We have attempted to find evidence for gender differences that could alter the information we have provided in this chapter but we could not find reliable human studies in this regard, This does not include differences that may exist in the endothelium or in the coronary artery anatomy or in the pathophysiology of atherosclerosis, but refers to effectiveness of antiplatelet and anticoagulation drugs as compared to the opposite sex. 

Inoue M, Itoh H, Ueda M, etal, Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions possible pathophysiological significance ofVEGF in progression of atherosclerosis. Circulation 1998 98(20) 2108-21 16. 

Barger AC, Beeuwkes R, Lainey LL, Silverman KJ. Hypothesis vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. N Engl J Med 1984 3 10(3) 175-177. 

---