Arteriosclerosis Pathogenesis

THE ARTERY AND THE PROCESS OF ARTERIOSCLEROSIS Pathogenesis Edited by Stewart Wolf 1971... 

In the vasculature, ANG H not only increases contraction of smooth muscle cells, but is also able to induce vascular injury. This can be prevented by blocking NFkB activation [3] suggesting a link between ANG II and inflammation processes involved in the pathogenesis of arteriosclerosis (see below). Thus, ACE inhibitors not only decrease vascular tone but probably also exert vasoprotective effects. 

One main line of future research could be in the inhibitory/activating effect on key enzymes involved in the pathogenesis of arteriosclerosis. In particular, enzymes regulating signal transduction involved in phosphorylation of proteins, such as PKC and tyrosine protein kinase, seems to be somehow modulated by different polyphenols and may represent a possible target for polyphenol activity. 

The effects of chronic hypertension on the human organism are, with one exception, of little interest to the investigator studying pathogenesis, although of great import to the sufferer and his physician. That exception is failure of the kidneys. Disease and failure of the heart are probably caused by chronic overstrain, often associated with another metabolic disease, arteriosclerosis of the coronary arteries. They account for about two thirds of the deaths primarily due to hypertension. Strokes of apoplexy, or cerebral vascular accidents, from rupture or thrombosis of a cerebral artery weakened by disease cause another sixth, uremia about one twelfth, and other conditions the remainder (28). Except for uremia, these events are usually the result of overwork and increased arterial tension. Only rarely does the heart escape hypertrophy. 

McCully KS Vascular pathology of homocysteine-mia implications for the pathogenesis of arteriosclerosis.Am J Pathol 56 111-128,1969. 

Since Johann Lobstein first coined the term arteriosclerosis, or hardening of the arteries in 1833, to the Framingham Study which began in 1948 (42), to the isolation of mevastatin by Akira Endo in 1976 (43), and on to the publication of the Scandinavian Simvastatin Survival Study (4S) in 1994 (44), cholesterol levels have emerged as perhaps the most potent modifiable risk factor in the treatment of chronic ischemic heart disease. Genetic disorders such as homozygous familial hypercholesterolemia where severe atherosclerosis is present by early adolescence have helped clarify the importance of LDL cholesterol in the pathogenesis of atherosclerosis. 

Small, D.M. 1988. Progression and regression of atherosclerotic lesions. Arteriosclerosis 8 103-129. Aikawa, M., Libby, P. 2004. The vulnerable atherosclerotic plaque pathogenesis and therapeutic approach. 

Hopeee SM, Sundeeman FW JR, McCully KS, Reid MC, Libee C, Speaes JR and Serur J (1984b) Studies of the pathogenesis of arteriosclerosis induced in rats by intrarenal injection of a carcinogen, nickel subsulfide. Ann Clin Lab Sd.l4 355-365. 

Maity of the food-derived extracts found to prevent cancer also typically have benefits in reducing morbidity from other diseases. For example, grape juice extract, which is a promising lead cancer preventive agent, has also been documented to reduce markers of coronary heart disease. Snch extracts inhibited the oxidation of LDL in vitro and conld have profound effects in reducing the risk of coronary heart disease, since the oxidation of LDL has been implicated in the pathogenesis of arteriosclerosis. ... 

Cardiovascular disease (CVD) continues to take a heavy toll on people in the productive period of life, especially in industrialized countries. Although its incidence has fallen in the last decade, CVD is still the main cause of death in industrialized countries. In the United States and many other countries, it is the number one chronic condition requiring hospitalization, and is also the most prevalent disease condition in the elderly. Despite intensive research, the etiology and the pathogenesis of arteriosclerosis and its consequences are not completely understood. An important causative factor is hypercholesterolemia, and cUnical intervention studies have demonstrated the therapeutic value of correcting it. However, at any given level of hypercholesterolemia, even in combination with all other classical risk factors such as hypertension or smoking, there is considerable variation in the expression of the disease. 

Acute rejection usually occurs within the first year after transplantation and is characterized by an intense cellular immune response within the graft. Acute rejection can usually be treated effectively with anti-inflammatory and anti-T-cell therapies. However, recurrent episodes of acute rejection may result in graft destruction or may lead to the development of chronic rejection. Chronic rejection usually occurs years after transplantation and is manifested by progressive loss of graft function, arteriosclerosis, and fibrosis. Whereas the pathogenesis of chronic rejection is not clear, both immunological and nonimmunological mechanisms seem to be involved (7). Based on the available data, chemokines are most likely to play a role in acute and chronic rejection as indicated schematically in Fig. 1. 

A substance with similar immunological properties has been found in the kidney, where it is more abundant in the cortex than in the medulla. According to Boyce and King [90, 91], the mucoprotein is consistently found in the kidneys of patients with recently formed stones, but is rarely present in patients with other kidney diseases in which stones are not formed (e.g., renal carcinoma and severe renal arteriosclerosis). The mucoprotein has not been detected in normal kidneys or in patients with pyelonephritis, and the compound cannot be immunologically detected in blood serum, human saliva, or bone matrix. The only other tissue where this matrix substance has been detected is the intestine. (Boyce and King think that this is not a coincidence and that the reason for its presence in kidney and intestine is that both these organs are involved in calcium absorption.) But most important to the pathogenesis of lithiasis are the mucopolysaccharides found in urine. 

McCully K.S., 1969. Vascular pathology of homocysteinemia implications for the pathogenesis of arteriosclerosis. Am J Pathol. 56 111-128. 

The purpose of this course was to gather information and to draw attention to the role of diet in the pathogenesis of experimental and human arteriosclerosis, as well as its prevention and therapy. 

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