How Do We Prevent the Vulnerable Atherosclerotic Plaque From Rupturing? Insights From In Vivo Assessments of Plaque, Vascular Remodeling, and Local Endothelial Shear Stress

Coronary atherosclerosis progresses both as slow, gradual enlargement of focal plaque and also as a more dynamic process with periodic abrupt changes in plaque geometry, size, and morphology. Systemic vasculoprotective therapies such as statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents are the cornerstone of prevention of plaque rupture and new adverse clinical outcomes, but such systemic therapies are insufficient to prevent the majority of new cardiac events. Invasive imaging methods have been able to identify both the anatomic features of high-risk plaque and the ongoing pathobiological stimuli responsible for progressive plaque inflammation and instability and may provide sufficient information to formulate preventive local mechanical strategies (eg, preemptive percutaneous coronary interventions) to avert cardiac events. Local endothelial shear stress (ESS) triggers vascular phenomena that synergistically exacerbate atherosclerosis toward an unstable phenotype. Specifically, low ESS augments lipid uptake and catabolism, induces plaque inflammation and oxidation, downregulates the production, upregulates the degradation of extracellular matrix, and increases cellular apoptosis ultimately leading to thin-cap fibroatheromas and/or endothelial erosions. Increases in blood thrombogenicity that result from either high or low ESS also contribute to plaque destabilization. An understanding of the actively evolving vascular phenomena, as well as the devel...
Source: Journal of Cardiovascular Pharmacology and Therapeutics - Category: Cardiology Authors: Tags: Review Article Source Type: research