Our data suggest that (i) apoC-III inhibition increases the stability of vulnerable plaques as shown by a reduction in necrotic core area and increase in SMC content and fibrous cap thickness, (ii) this effect is dependent on triglyceride lowering via improved TRL clearance, (iii) increased insulin sensitivity is associated with reduced necrotic core area and increased SMC content, and (iv) apoC-III deficiency in conjunction with diet intervention prevents the progression of atherosclerosis. This evidence concerns the gene APOC3 and atherosclerosis.