Towards understanding acute destabilization of vulnerable atherosclerotic plaques

The current wisdom is that destabilization of human atheromatous fibroinflammatory plaques may result in thrombosis and is responsible for most acute ischemic syndromes. This paradigm has led to vigorous research to understand the pathogenesis of plaque vulnerability and subsequent rupture, to find reliable systemic serological markers and to identify imaging techniques in order to determine vulnerability of individual plaques.

Research examining the pathobiology of the vulnerable plaque and its subsequent destabilization is described. Investigations are based on the current understanding of vascular cell and molecular biology and clinical paradigms of acute coronary syndromes.

It is apparent that there are three steps that need to be considered. These are transformation of a stable plaque into a vulnerable plaque, destabilization of a vulnerable plaque and regulation of the complications following destabilization, the most serious being acute occlusive thrombosis. In vitro cell and molecular vascular biology studies, and animal model studies that alter specific gene(s) expression, have provided new knowledge on putative mechanisms leading to plaque vulnerability and on subsequent destabilization of the plaque. These studies show that several local and systemic factors, including inflammation, matrix disruption, lipid deposition, cell necrosis and apoptosis are likely to play a role in vulnerability, destabilization and clinical syndromes.

Plaque vulnerability and destabilization is of multifactoral etiology with inflammation, cap matrix and necrotic lipid core remodeling being important pathobiological processes associated with vulnerability and destabilization. Identifying gene-environment interactions, improving imaging techniques and improving our understanding of the mechanisms underlining plaque pathogenesis via animal models are essential elements for understanding human plaque vulnerability and destabilization.