Abstract
Lipoprotein lipase (LPL) plays a major role in the lipid homeostasis mainly by mediating the intravascular lipolysis of triglyceride rich lipoproteins. Impaired LPL activity leads to the accumulation of chylomicrons and very low-density lipoproteins (VLDL) in plasma, resulting in hypertriglyceridemia. While low-density lipoprotein cholesterol (LDL-C) is recognized as a primary risk factor for atherosclerosis, hypertriglyceridemia has been shown to be an independent risk factor for cardiovascular disease (CVD) and a residual risk factor in atherosclerosis development. In this review, we focus on the lipolysis machinery and discuss the potential role of triglycerides, remnant particles, and lipolysis mediators in the onset and progression of atherosclerotic cardiovascular disease (ASCVD). This review details a number of important factors involved in the maturation and transportation of LPL to the capillaries, where the triglycerides are hydrolyzed, generating remnant lipoproteins. Moreover, LPL and other factors involved in intravascular lipolysis are also reported to impact the clearance of remnant lipoproteins from plasma and promote lipoprotein retention in capillaries. Apolipoproteins (Apo) and angiopoietin-like proteins (ANGPTLs) play a crucial role in regulating LPL activity and recent insights into LPL regulation may elucidate new pharmacological means to address the challenge of hypertriglyceridemia in atherosclerosis development.
Highlights
There are three main lipids in the blood: cholesterol, phospholipids, and triglycerides.Cholesterol is important for the synthesis of bile acids and steroids and for maintaining the integrity of cell membranes, while phospholipids are a major component of all cell membranes
Adipocytes and myocytes are the prime sources of Lipoprotein lipase (LPL) production and because these cells are located distantly from the capillary lumen, where LPL acts on marginated lipoproteins, it needs to be trafficked across the subendothelial space and trancytosed across the endothelial cells [14,26]
As a supplement to dietary restrictions, it has proven highly beneficial in patients with familial chylomicronemia syndrome (FCS) lowering TGs levels by 70–80% [140,141] and this represents a promising start for future drugs targeting ApoC-III
Summary
There are three main lipids in the blood: cholesterol, phospholipids, and triglycerides. Each class of lipoprotein serves distinct roles in the lipid metabolism (Figure 1); (i) the large chylomicrons and VLDLs are responsible for the transport and delivery of energy rich TGs, (ii) LDL deposits cholesterol in tissues, and (iii) HDL absorbs cholesterol and transports it back to the liver for degradation and redistribution (Figure 1). Data have shown that when LPL is expressed by macrophages in the vessel wall it displays pro-atherogenic effects [12] With this in mind, there is a great need to understand the underlining molecular mechanism(s) causing increased triglyceride levels in hypertriglyceridemia and atherosclerosis and map the complex regulation of LPL.
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