Remnant Lipoproteins As Strong Key Particles to Atherogenesis

Abstract

Recent epidemiologic studies have revealed that hypertriglyceridemia is associated with atherosclerosis independent of other coronary risk factors. However, it is difficult to select patients at high risk for coronary artery disease using only serum triglyceride levels compared with low-density lipoprotein cholesterol levels since multiple factors are associated with elevating triglycerides. Atherosclerotic diseases with high triglyceride levels can be found in patients with familial combined hyperlipidemia, diabetes mellitus, and metabolic syndrome, in which remnant lipoproteins accumulate in the circulating blood. Recent researches have paid attention to remnant lipoproteins as atherogenic particles with the development of methods for measuring remnant cholesterol levels and apolipoprotein B-48 levels directly from human serum. Measurement of these parameters in addition to serum triglycerides may help to distinguish high-risk patients and enable us to prevent or suppress the progression of atherosclerotic diseases in those patients. However, questions remain to be answerd to evaluate the significance of remnant lipoproteins. Here, we focus on three issues: the underlying problems in measuring remnant lipoprotein cholesterol, the assessment of postprandial hyperlipidemia as an atherogenic condition, and finally a review of our experimental and clinical findings about the mechanisms by which remnant lipoproteins induce atherosclerosis.

Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies

“…The atherogenic effects of RLPs on the endothelium include upregulation of proinflammatory cytokines, monocyte recruitment and activation, and increased production of prothrombotic factors 4. Changes in RLPs in the postprandial state may lead to endothelial dysfunction as measured by flow‐mediated dilation 40.…”

“…Though not as well recognized as LDL particles for their role in atherogenesis, RLPs have several proatherogenic properties, including proinflammatory and prothrombotic effects; in addition, resident macrophages scavenge and retain RLPs in the subendothelial space 4, 5, 6, 7…”

Upregulation of hepatic LRP1 by rosiglitazone: a possible novel mechanism of the beneficial effect of thiazolidinediones on atherogenic dyslipidemia

“…Increased triglyceride-rich lipoproteins, such as chylomicron and VLDL, are hydrolyzed to remnant particles (Merkel 2009). Recent studies have focused on these remnant lipoproteins as atherogenic particles, showing that remnant lipoproteins can penetrate the endothelial wall and remain in the subendothelial space (Fujioka & Ishikawa 2009). Remnant lipoproteins have also been reported to be associated with inflammation, endothelial dysfunction, foam cell formation, and vascular smooth muscle cell proliferation (Fujioka & Ishikawa 2009).…”

“…Recent studies have focused on these remnant lipoproteins as atherogenic particles, showing that remnant lipoproteins can penetrate the endothelial wall and remain in the subendothelial space (Fujioka & Ishikawa 2009). Remnant lipoproteins have also been reported to be associated with inflammation, endothelial dysfunction, foam cell formation, and vascular smooth muscle cell proliferation (Fujioka & Ishikawa 2009). Several studies have reported that the level of remnant-like particle cholesterol (RLP-C) is increased in diabetic patients (Taniguchi et al 2000, Schaefer et al 2002 and is associated with an increased risk of cardiovascular disease (Fukushima et al 2001(Fukushima et al , 2004.…”

Thyroid Function Influences Serum Apolipoprotein B-48 Levels in Patients with Thyroid Disease

“…Many basic studies have suggested that accumulated CMR particles may promote atherogenicity in the arterial wall. Indeed, elevated intestinally derived remnant lipoproteins have been associated with an increased risk for cardiovascular diseases 25,26) . CM and CMR have a characteristic apolipoprotein B-48 (apoB-48), each having one apoB-48 molecule per particle.…”