Vascular Biology of Acute Coronary Syndromes

Thrombus formation in a coronary artery with obstruction of coronary blood flow and reduction in oxygen supply to the myocardium produces the acute coronary syndromes (ACSs). These thrombotic episodes largely occur in response to atherosclerotic lesions that have progressed to a high risk-inflammatory/prothrombotic stage. Although apparently distinct, the atherosclerotic and thrombotic processes appear to be closely interrelated as the causal presentation of ACS through a complex multifactorial process named atherothrombosis. ACS represents a spectrum of ischemic myocardial events that share similar pathophysiology and include unstable angina, nonQ-wave myocardial infarction, Q-wave myocardial infarction, and sudden death. Atherosclerosis is a chronic systemic disease involving the intima of largeand medium-sized arteries including the aorta, carotids, coronaries, and peripheral arteries, which is characterized by intimal thickening due to cellularand lipid-accumulation [1]. Endothelial dysfunction and inflammation are the major facilitators of atherosclerotic disease progression. Lipid accumulation results from an imbalance between mechanisms responsible for lipid influx and efflux. Secondary changes may occur in the underlying media and adventitia, particularly in advanced disease stages. Indeed, fibroblasts from the adventitia have been shown to have an important partnership with the medial smooth muscle cells (SMCs), resulting in neointima formation and compensatory vascular enlargement (remodeling). The early atherosclerotic lesions might progress without compromising the lumen due to this remodeling [2]. When fatty streaks progress to fibroatheroma, they develop a cap of SMCs and collagen, and when this plaque is disrupted, the subsequent thrombus formation is the first step of ACS and strokes. Importantly, the culprit lesions leading to ACS are usually mildly stenotic and therefore are poorly detected by angiography [3]. The composition of the plaque, rather than the stenosis, appears to be the main determinant of risk of plaque rupture and following thrombogenicity. High-risk rupture-prone lesions usually have a large lipid core, a thin fibrous cap, high density of inflammatory cells (particularly at