Genes potentially involved in plaque rupture

Rupture of an atherosclerotic plaque is the predominant underlying event in the pathogenesis of acute coronary syndromes and stroke. While ruptured plaques are morphologically well described, the precise molecular mechanisms involved in plaque rupture are still incompletely understood. Over the last few years, techniques like microarray, suppression subtractive hybridization and differential display enabled us to study complex gene expression profiles that occur during the process of atherogenesis. In this review we focus on recent large-scale gene expression profiles performed on whole mount vascular specimens.

The gene expression profiles on whole mount vascular tissue confirmed that at least three mechanisms are involved in plaque rupture: (1) a disturbed balance in extracellular matrix turnover, (2) disturbed regulation of cell turnover and (3) processes involved in lipid metabolism. Animal models exhibiting features of plaque rupture reflect the involvement of these three mechanisms. The most dramatic mouse phenotypes were observed after interventions in at least two of these mechanisms.

The observation of plaque rupture in recent mice models is indicative of the multifactorial process of plaque rupture. This multifactorial character of plaque rupture suggests that interventions may be most effective when they influence more than one mechanisms at a time.