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The discovery of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, called statins, was a breakthrough in the prevention of hypercholesterolemia and related diseases. Hypercholesterolemia is considered to be one of the major risk factors for atherosclerosis which often leads to cardiovascular, cerebrovascular and peripheral vascular diseases. The statins inhibit cholesterol synthesis in the body and that leads to reduction in blood cholesterol levels, which is thought to reduce the risk of atherosclerosis and diseases caused by it. == History == More than 100 years ago a German pathologist named Rudolf Virchow discovered that cholesterol was to be found in the artery walls of people that died from occlusive vascular diseases, like myocardial infarction. The cholesterol was found to be responsible for the thickening of the arterial walls and thus decreasing the radius in the arteries which leads in most cases to hypertension and increased risk of occlusive vascular diseases.〔 In the 1950s the Framingham heart study led by Dawber revealed the correlation between high blood cholesterol levels and coronary heart diseases. Following up from that study the researchers explored a novel way to lower blood cholesterol levels without modifying the diet and lifestyle of subjects suffering with elevated blood cholesterol levels. The primary goal was to inhibit the cholesterol biosynthesis in the body. Hence HMG-CoA reductase (HMGR) became a natural target. HMGR was found to be the rate-limiting enzyme in the cholesterol biosynthetic pathway. There is no build-up of potentially toxic precursors when HMGR is inhibited, because hydroxymethylglutarate is water-soluble and there are alternative metabolic pathways for its breakdown.〔 In the 1970s the Japanese microbiologist Akira Endo first discovered natural products with a powerful inhibitory effect on HMGR in a fermentation broth of ''Penicillium citrinum'', during his search for antimicrobial agents. The first product was named compactin (ML236B or mevastatin). Animal trials showed very good inhibitory effect as in clinical trials, however in a long term toxicity study in dogs it resulted in toxic effects at higher doses and as a result was believed to be too toxic to be given to humans. In 1978, Alfred Alberts and colleagues at Merck Research Laboratories discovered a new natural product in a fermentation broth af ''Aspergillus terreus'', their product showed good HMGR inhibition and they named the product mevinolin, which later became known as lovastatin.〔〔 The cholesterol controversy began in the early promotion of statins (history ) 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Discovery and development of statins」の詳細全文を読む スポンサード リンク
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