Molecular phenotypes of atherosclerosis: fingering the perpetrators.

Abstract

The initiation and progression of atherosclerosis appears driven by a combination of genetic and environmental factors. Access to circulating lipoproteins or to molecules shed into the blood from arterial wall cells permits genetic diversity to be evaluated in relation to disease risk; environmental factors are commonly understood to relate to macro-risk such as diet, smoking, etc. However, a more precise and detailed understanding of the genetic and in vivo environment in the immediate vicinity of the predictive, developing, or advanced lesion is desirable. The presence at autopsy of atherosclerotic lesions of varying severity and classifications1 within the same individual reflects the complexity of this chronic inflammatory process. Furthermore, certain arterial locations are predictive for lesion formation before any detectable pathological change is apparent, whereas other sites appear to be protected.2,3 Systematic and serendipitous studies of genetic variants associated with atherogenesis have largely been conducted in lipoproteins and blood cells, yet genetic variation in the arterial wall components is an important contributor to disease susceptibility and progression. The most prevalent gene expression changes may identify the inheritance of multiple gene variants as a collection of single nucleotide polymorphisms (SNPs) that may predict both the susceptibility to environmental risk factors and the characteristics of lesion progression. However, the development …