The plaque stabilising effects of Apolipoprotein A-IV

Abstract

Apolipoprotein A-IV (apoA-IV) has antioxidant, anti-apoptotic, and anti-inflammatory properties. It also facilitates cholesterol efflux and promotes plaque regression. There is limited information regarding its effects on plaque stability and human vascular smooth muscle cell (VSMC) phenotype. After twice-weekly injections of human lipid-free apoA-IV (1mg/kg, n=31) or PBS (n=32) during the 9th–10th week of high-fat diet, plaques within brachiocephalic arteries of 16-week old apoE-KO C57BL/6 mice demonstrated fewer plaque ruptures, thicker fibrous caps, smaller lipid cores, lower macrophage:SMC ratio, less MMP-9, more collagen, less proliferating cells, less apoptosis and lower MCP-1, VCAM-1 and iNOS levels. In cultured human monocyte-derived macrophages, MMP-9 and TIMP-1 expression were decreased after treatment with apoA-IV (0.2 mg/ml) overnight. These favoured a more stable plaque. Vascular smooth muscle cells, grown in serum-deficient medium (0.2% FBS) for three days prior to stimulation using PDGF-BB (30 ng/ml) for 24 hours received human lipid-free apoA-IV (0.2 mg/ml) or PBS for 48 hours. ApoA-IV was associated with several significant process: increase in myocardin mRNA expression, decrease in VCAM-1 and S100A4 mRNA expression, reduction in width-to-length ratio, decrease in MMP-9 activity, reduction in migratory activity and more viable cells. Taken together, apoA-IV favoured the differentiated phenotype in VSMCs.