Adipophilin Expression Is Increased in Symptomatic Carotid Atherosclerosis

Abstract

Adipophilin is an adipose differentiation-related protein expressed in lipid-containing cells. Using DNA microarray analysis, we previously found the adipophilin gene (ADFP) to be overexpressed in symptomatic carotid plaques (CP). This led us to further examine the role of adipophilin in carotid atherosclerosis relative to symptom status. Ninety-eight high-grade (>70%) CPs were obtained in carotid endarterectomy. The relative expression of ADFP mRNA was measured by quantitative real-time RT-PCR, and the relative amount of adipophilin protein was quantified with Western blotting. Detailed topographical correlations with extravasated red blood cells and extracellular cholesterol crystals were obtained by means of immunohistochemistry. The relative expression of ADFP mRNA was increased in symptomatic compared with asymptomatic CPs at both the mRNA level (1.82+/-0.19[SE] versus 1.25+/-0.15, P=0.012) and the protein level (1.04+/-0.23 versus 0.46+/-0.14, P=0.043). Adipophilin colocalized with macrophage foam cells, extravasated red blood cells (P<0.0001), and cholesterol crystals (P<0.0001), and its expression associated with macroscopic ulceration of CP (P<0.0001). Intraplaque hemorrhages may contribute to intracellular lipid accumulation and consequent adipophilin expression. Because adipophilin blocks cholesterol efflux from lipid-laden cells, they may die and develop a necrotic lipid core, thereby destabilizing the plaque.