Abstract
Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.
Highlights
Acute coronary syndromes (ACS) are the main cause of morbidity and mortality in western societies
Apoe-/- mice were subjected to alteration of blood flow in the left common carotid artery (LCCA) by partial ligation (Fig 1A) or implantation of a shear stress modifier as described in [9]
Post-mortem analyses of human specimens have defined the characteristics of the archetypical vulnerable plaques responsible for most of the thrombotic events associated with ACS
Summary
Acute coronary syndromes (ACS) are the main cause of morbidity and mortality in western societies. Thrombotic events associated to plaque rupture are responsible of the majority of ACS events [1, 2]. Rupture-prone plaques are archetypically characterized by exacerbated infiltration of inflammatory leukocytes in combination with a large necrotic core (NC) covered by a thin fibrous cap (FC) [3]. During plaque destabilization, enhanced macrophage and vascular smooth muscle cell (VSMC) apoptosis fuel the NC enlargement. Extracellular matrix degradation and VSMC apoptosis induction by lesional proteases results in the loss of the FC stability [4]. Structural damage in the FC results in the exposure of the highly thrombogenic material of the NC to the blood, leading to thrombus formation, occlusion of the coronary artery, and associated ACS [5]. Albeit the clinical relevance of this process, the PLOS ONE | DOI:10.1371/journal.pone.0141019 October 22, 2015
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