Cardiovascular Diseases (CVD) are the currently the leading cause of death globally for both men and women accounting for 21.9 per cent of total deaths and is projected to increase to 26.3 per cent by 2030 . Statins are the treatment of choice for the primary and secondary prevention of cardiovascular disease and in the management of hypercholesterolaemia because of their proven efficacy and safety profile. Evidences are showing their effectiveness in reduction of cholesterol synthesis and number of pleiotropic effects, which may be cholesterol dependent and cholesterol independent. The present review focus on the origin, properties and effects of statins on endothelial function ( non lipid action of statins) through the increase of endogenous production of NO in different pathways.
Key words: Coronary artery Disease (CAD), Statins, Endothelium, Caveolin.
Coronary artery disease (CAD) is the most common type of multifactorial chronic heart disease. It is a consequence of plaque buildup in coronary arteries. The arterial blood vessels, which begin out smooth and elastic become narrow and rigid, curtailing blood flow resulting in deprived of oxygen and nutrients to the heart .
CAD is a leading cause of morbidity and mortality throughout the worldwide. The prevalence of biological and metabolic risk factors were also found to be high in development of coronary artery disease. Patients with hypercholesterolemia are at increased risk to experience cardiovascular events and to die from vascular disease . .Statins, among the most commonly prescribed drugs worldwide, are cholesterol let downing agents used to manage cardiovascular and coronary heart diseases and to treat hypercholesterolemia. Statin’s therapy markedly reduces the relative incidence of acute coronary events in patients with coronary artery disease [3,4].
Although statins are approved only for the treatment of lipid disorders, there is increasing evidence that they may be useful in the treatment of other conditions, such as Alzheimer’s disease, osteoporosis, cancer etc.,However statins not only lower cholesterol, but also have been reported to exhibit pleiotropic effects .
History & Properties of Statins
Dr. Akira Endo and Masao Kuroda of Tokyo, Japan were the pioneers in the discovery of statins. The isolated prototype agent was “compactin” (Mevastatin ML-23613) from the fungus “penicillin citrinum” ( in japan 1976) and the first commercially marketed statins was lovastatin (Mevinolin MK 803) extracted from “Aspergillus terreus ” by Merck in 1978 . Clinical relevance to Endo’s discovery was accomplished by the studies of Joseph Goldstein and Michael Brown, who discovered a cellular receptor for LDL (LDL-R), received the noble prize in 1985 .
Statins can be classified as First, Second and Third generation based on their clinical efficacy. First generation statin drugs includes Lovastatin (Fungal derivative ),...