Biomarkers for Atherosclerotic Diseases: Significance of Intimal Smooth Muscle Cell-Derived Circulating Marker

Vascular cells with the active molecules they release are involved in the progression of atherosclerosis. These cell-related circulating markers are expected to reflect the pathological conditions of atherosclerotic lesions. In response to stimuli from other cells or active molecules, smooth muscle cells (SMCs) in the medial layer change their phenotype from contractile to synthetic, migrate from the media into the intima, and there they proliferate and release various kinds of cytokines, proteinases, and extra-cellular matrices. Thus, the functions of intimal SMCs are believed to play key roles in plaque formation. The incomplete or sustained activation of intimal SMCs may cause the fragility of plaques under pathological conditions, i.e., diabetes and dyslipidemia. LR11 is one of the genes specifically expressed in intimal SMCs, but not in me- dial SMCs, and it increases the sensitivity of intimal SMCs to migration in response to cytokines including angiotensin II. The soluble form of LR11 is in circulation, and the levels increase transiently after coronary intervention in the period corresponding to the migration of SMCs. The increase in initial sLR11 levels is negatively correlated with event-free survival for CVD endpoints. These results suggest that biomarkers reflecting the pathological conditions of intimal SMCs may be useful as surrogate and/or companion markers for the treatment of atherosclerotic diseases. [Review].