Enhanced Intestinal Absorption of Cholesterol along with Increased Chylomicron Remnants for De novo Progression of Coronary Stenosis

Serum concentrations of low-density lipoprotein (LDL) cholesterol and total cholesterol (TC) are influenced by cholesterol production from the liver and cholesterol absorption in the intestine. As shown in an epidemiological study, both decreased cholesterol synthesis and increased cholesterol absorption in the intestine are significant and independent predictors of prevalent coronary heart disease (CHD) relative to established coronary risk factors 1). Patients with hyper-LDL cholesterolemia are usually treated using statins for the prevention of CHD, and the long-term use of statins enhances the cholesterol absorption in the intestine by the feedback inhibition of cholesterol production by the liver. An increased cholesterol content in intestinal epithelial cells may cause increased production of chylomicron (CM), resulting in hypertri-glyceridemia and the accumulation of CM remnants in the postprandial sera (Fig. 1). Similar to small, dense LDL or very-low-density lipoprotein remnants, CM remnants are related to atherogenicity by enhancing systemic inflammation, platelet activation, coagula-tion, thrombus formation, and macrophage foam cell formation 2). Concentration of the fasting apolipopro-tein (apo)B-48, which is a quantitative marker for CM remnants 3) , correlates with carotid intima-media thickening 4) and the prevalence of chronic 5) and new-onset coronary artery disease (CAD) 6). Therefore, both the increased intestinal cholesterol absorption and the accumulation of CM remnants are considered to be high-risk status for CHD events in the statin treatment ; however, it is unclear whether these markers were also useful for the prognosis of coronary events for secondary prevention. Recently, percutaneous coronary intervention (PCI), including stenting, has been established as a standardized treatment for improving angina and activity of daily life in Japanese patients with CHD. The importance of cholesterol-lowering therapy, including high-dose statin therapy, in patients with CHD has been long emphasized. It was shown that aggressive lipid-lowering therapy is at least as effective as PCI in reducing CHD events in patients with hyper-LDL cholesterolemia and mild coronary steno-sis (asymptomatic or mild-to-moderate angina) 7). On the other hand, the correlation between the accumulation of remnant lipoproteins and the development of coronary stenosis is not known. Moreover, coronary stenosis after PCI involves de novo stenosis and in-stent restenosis after the stenting of drug-eluting stents or bare-metal stents, and there is no data on which kind of coronary stenosis is correlated with the accumulation of CM remnants. If we can truly understand these correlations, we can develop useful strategies for the prevention of coronary stenosis in relation to the atherogenic characteristics of …