Cardiovascular disease (CVD) is currently the leading cause of death globally for both men and women, accounting for 21.9% of total deaths and is expected to increase at 26.3% by 2030. Statins represent the treatment of choice for the primary and secondary prevention of cardiovascular diseases and in the management of hypercholesterolemia thanks to their proven efficacy and safety profile. Evidence is demonstrating their effectiveness in reducing cholesterol synthesis and the number of pleiotropic effects, which can be cholesterol-dependent and cholesterol-independent. The present review focuses on the origin, properties and effects of statins on endothelial function (non-lipid action of statins) through increasing endogenous NO production in different pathways. Keywords: 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 the accumulation of plaque in the coronary arteries. Arterial blood vessels, which initially are smooth and elastic, become narrow and stiff, reducing blood flow resulting in deprivation of oxygen and nutrients to the heart [1]. CAD is a major cause of morbidity and mortality worldwide. The prevalence of biological and metabolic risk factors was also high in the development of coronary heart disease. Patients with hypercholesterolemia are at increased risk of experiencing cardiovascular events and dying from vascular diseases [2]. Statins, among the most commonly prescribed drugs worldwide, are cholesterol-lowering agents used to manage cardiovascular and coronary heart disease and to treat hypercholesterolemia. Statin therapy ...... half of the document ...... and forms an inhibitory complex with caveolin-1 leads to a decrease in the activity of the enzyme in cells. Transcription of the Cav-1 gene is regulated by cholesterol-sensitive elements. Exposure of fibroblasts and endothelial cells to free cholesterol and LDL cholesterol was found to regulate Cav-1 expression. Ca+2 mobilizing agents cause disinhibition of and NOS by promoting Ca+2/calmodulin-triggered Cav-1 dissociation. Statin downregulates Cav-1 in endothelial cells by blocking cholesterol synthesis, a favorable effect on vascular function may in part mediated by disruption of the eNOS/Cav-1 complex [24]. ConclusionIn summary, evidence accumulated from various research and Clinical studies indicate that statins have pleiotropic effects and improve endothelial function through increasing endogenous NO production in several pathways.