Remnant-like lipoprotein particles impair endothelial function: direct and indirect effects on nitric oxide synthase

Abstract

Remnant-like lipoprotein particles (RLPs) have been implicated as potentially atherogenic lipoproteins. Endothelial dysfunction is known to be an early event in atherosclerosis and an important contributor to the pathogenesis of coronary artery disease. Moreover, there is considerable evidence linking increased RLP cholesterol levels with endothelial dysfunction, reflected by impaired endothelial vasodilatation and abnormal endothelial secretion Remnant-like lipoprotein particles (RLPs), also known as remnant lipoproteins or remnant-like particles, are derived from VLDLs and chylomicrons, which are the major carriers of plasma triglycerides. The actions of lipoprotein lipase and cholesteryl ester transfer protein on VLDL and chylomicrons produce RLPs with decreased triglyceride and increased cholesteryl ester and apolipoprotein E (apoE). Compared with the nascent triglyceride-rich lipoproteins, RLPs are smaller particles, with a higher density and more cholesteryl ester, which seems to give them more potential atherogenic properties.RLPs have been separated on the basis of their size, density, charge, specific lipid components, or apolipoprotein composition. The analytical "gold standard" for measuring triglyceride-rich lipoproteins and remnants is density gradient ultracentrifugation; however, this technique is laborintensive and involves a 24 h analysis to fractionate the plasma lipoproteins. Moreover, only a few samples can be processed at the same time in each ultracentrifuge. Tsai et al.(1) used NMR spectroscopy to perform numerous postprandial analyses of triglyceride-rich lipoproteins in a large interventional study, and observed that chylomicrons and chylomicron remnants/VLDL fraction measurements obtained by NMR had a high degree of correlation with results produced by ultracentrifugation. NMR is a more rapid procedure and uses substantially less sample volume than traditional ultracentrifugation. And NMR is a physical procedure, so that plasma samples can be preserved for biochemical assays of stable analytes. However, NMR is a relatively expensive method, with a special analyzer, and is not widely available in clinical laboratories at present.Recently, a novel immunoseparation method for RLPs has been developed (2). This method uses two monoclonal antibodies, to human apoB-100 and apoA-I, respectively, to remove most of the apoB-100-containing lipoproteins

Lipoprotein lipase: From gene to atherosclerosis

“…It is well established that oxidized low-density lipoproteins (ox-LDL) plays a role in atherogenesis by inducing EC apoptosis and increasing endothelial permeability [138]. Recently, it has also been revealed that remnant lipoprotein particles impair endothelial function via direct and indirect effects on endothelial nitric oxide synthase (eNOS) and by stimulating secretion of inflammatory factors, such as CRP, IL-6, and TNF-a, from multiple origins [139]. Remnant lipoproteins may accelerate senescence of endothelial progenitor cells through inhibiting telomerase activity via the reactive oxygen species-dependent pathway or altering microRNA levels eventually resulting in endothelial dysfunction and promoting the entry and retention of remnant lipoprotein particles in the vessel wall [140,141].…”

Vascular endothelium in atherosclerosis

“…The RLp may affect the autophosphorylation of focal adhesion kinase and its downstream phosphatidylinositol kinase/Akt signalling pathway, resulting in direct eNOS inactivation through the induction of intracellular ROS. In addition, RLp might indirectly affect the expression or activation of eNOS by stimulating secretion of various inflammatory factors (for a review, see Zheng and Liu 2007).…”

Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: A review of the literature

“…These elevated levels of TG-rich lipoproteins and their remnants have been shown to be linked to plaque formation and progression [16]. TG-rich lipoprotein remnants are also thought to contribute to the progression of atherosclerosis by indirect mechanisms such as impaired vasodilation and increased inflammation [5,[17][18][19][20].Therefore, the management of hypertriglyceridemia is important not only in the prevention of pancreatitis, but also in reducing the risk of CVD in patients with mild to moderate hypertriglyceridemia.The addition of niacin, fibrates, or long-chain omega-3-fatty acids to statin therapy has been advocated for those hypertriglyceridemic patients who have not attained normal TG levels [4][5][6][7][8][9]. However, these agents often differ substantially in their TG-lowering effects and associated adverse effects.…”

“…These elevated levels of TG-rich lipoproteins and their remnants have been shown to be linked to plaque formation and progression [16]. TG-rich lipoprotein remnants are also thought to contribute to the progression of atherosclerosis by indirect mechanisms such as impaired vasodilation and increased inflammation [5,[17][18][19][20].…”