aInstitute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Discovery, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China
bDepartment of Pediatrics and Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
cDepartment of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The Cumming School of Medicine, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada
dDepartment of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
eSchool of Nursing, University of South China, Hengyang, Hunan 421001, China
Received 9 May 2014. Revised 13 October 2014. Accepted 13 October 2014. Available online 18 October 2014.
Highlights
This review provides a comprehensive and systematic introduction of LPL, from gene to AS.
•
This review covered the latest developments of LPL involving GPIHBP1, Angptl4, apoA-V and apoC-I/III.
•
We discussed the pro-atherogenic effect of LPL, which induce lipid accumulation and inflammation in arterial wall.
Abstract
Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and responsible for catalyzing lipolysis of triglycerides in lipoproteins. LPL is produced mainly in adipose tissue, skeletal and heart muscle, as well as in macrophage and other tissues. After synthesized, it is secreted and translocated to the vascular lumen. LPL expression and activity are regulated by a variety of factors, such as transcription factors, interactive proteins and nutritional state through complicated mechanisms. LPL with different distributions may exert distinct functions and have diverse roles in human health and disease with close association with atherosclerosis. It may pose a pro-atherogenic or an anti-atherogenic effect depending on its locations. In this review, we will discuss its gene, protein, synthesis, transportation and biological functions, and then focus on its regulation and relationship with atherosclerosis and potential underlying mechanisms. The goal of this review is to provide basic information and novel insight for further studies and therapeutic targets.
Graphical abstract
With the lipolysis of TRL by LPL, the released FFA and RLP may trigger inflammatory response, increase the arterial permeability and induce EC apoptosis. After entering into the arterial wall, RLPs can bind to proteoglycans and cell HSPG, promoting their retention. In the plaques, LPL produced by macrophages can further hydrolyze RLPs and facilitate their uptake, leading to lipid accumulation and foam cell formation. Taken together, they promote the development of AS.
Keywords
LPL
Lipoprotein
Lipid
Triglyceride
Inflammation
Atherosclerosis
Abbreviations
LPL, lipoprotein lipase
TG, triglyceride
CM, chylomicron
VLDL, very low density lipoprotein
FFA, free fatty acid
FA, fatty acid
ER, endoplasmic reticulum
LMF1, lipase maturation factor 1
SorLA, sortilin-related receptor with A-type repeats
TGN, trans Golgi network
LS, lysosome
HSPG, heparan sulfate proteoglycans
HS, heparan sulfate
EC, endothelial cell
VEC, vascular endothelial cell
VLDLR, very low density lipoprotein receptor
GPIHBP1, glycosylphosphatidylinositol-anchored high density lipoprotein–binding protein 1
PPRE, peroxisome proliferator activated receptor responsive element
No comments:
Post a Comment