Biochemical mechanisms underlying atherogenesis

Abstract

Atherosclerosis remains one of the major causes of death and premature disability in developed countries. Though atherosclerosis was formerly considered a bland lipid storage disease, substantial advances in basic and experimental sciences have illuminated the role of endothelium, inflammation and immune mechanisms in its pathogenesis. Current concept of atherosclerosis is that of a dynamic and progressive disease arising from injury to endothelium, also known as endothelial dysfunction and an inflammatory response to that injury. The lesions of atherosclerosis occur principally in large and medium sized arteries. Atherosclerosis affects various regions of the circulation preferentially and can lead to ischemia of heart, brain or extremities resulting in infarction. This produces distinct clinical manifestations depending on the vessel involved. Several predisposing factors to cardiovascular diseases such as diabetes mellitus, hypertension, obesity, infections act as triggers to the development of atherosclerosis by causing endothelial dysfunction and/or promoting inflammatory response. The evolution of pathogenetic mechanisms has passed through various directions such as oxidative stress, inflammation and immune responses. It is now known that all these are not acting independently but are interrelated and getting unified in the current concept of atherogenesis. The following discussion aims at providing an insight into these developments which can help in a better comprehension of the disease and management of its clinical complications.