Inflammation and Thrombosis in Coronary Atherosclerosis: Pathophysiologic Mechanisms and Clinical Correlations

Abstract

Inflammation and thrombosis are interrelated processes that are important in the pathogenesis of atherothrombosis. Inflammation is important in both the early and late stages of atherosclerosis, and it involves elements of immune system activation. Low density lipoprotein (LDL) is an important initiator but is not the only one. LDL enters the cell membrane, is modified, and sets into motion a series of events that stimulate the ingress of specific proinflammatory mononuclear cells through the vessel wall. These cells imbibe lipids and form foam cells. Proinflammatory mediators secreted by these cells can eventually lead to intimal thickening and lipid accumulation, forming atherosclerotic plaques. A complex interplay between inflammation, platelet function, and hypercoagulability is a major contributor to the progression from stable to unstable plaque and an acute coronary event. In the later stages of atherosclerosis, inflammatory cells can destabilise certain lipid-rich lesions contributing to symptomatic coronary thrombosis. Thus, thrombosis is the final common pathway for most atherosclerotic complications. Thrombi may also contribute to the asymptomatic rapid progression of atherosclerotic lesions. While antithrombotic agents are important in the treatment of acute coronary syndromes, as well as preventive therapy in high-risk primary prevention and in secondary prevention, the role of specific anti-inflammatory agents is not currently established. If such therapies are to become routine, these anti-inflammatory drugs must significantly reduce events while not adversely affecting a patient’s natural immunity to an extent that erases any potential benefit. This article reviews these two processes with an emphasis on coronary atherosclerosis and its sequelae.