Natural Polyketides to Prevent Cardiovascular Disease
In nature, statin compounds serve as a potent chemical defense mechanism employed by fungi to inhibit their competitors’ ability to synthesize cholesterol, a key component of normal cellular function. This is achieved through the inhibition of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the cholesterol biosynthesis pathway. In medicine, these polyketides and their derivatives are administered orally to inhibit the body’s endogenous cholesterol production. Since their discovery in the 1970s, statins have become a well-established and highly successful class of lipid-lowering agents. High lipid levels have been causatively associated with a number of health conditions. Statin drugs are widely used as both primary and secondary preventative treatments for cardiovascular diseases such as hypercholesterolemia, hyperlipidemia and atherosclerosis. Their potency and effectiveness have resulted in their success as one of the most profitable and widely used pharmaceuticals in history. The path leading to the discovery and development of statins is a valuable example of the potential of utilizing natural polyketides in the treatment of human diseases.