Lipoprotein Lipase(LPL)Gene Deficiency Related Diseases and Treatment Progress
Lipoprotein lipase(LPL)is an important rate-limiting enzyme in the metabolism of triglycerides in human lipoproteins.It is synthesized by parenchymal cells such as myocardium,skeletal muscle,and adipocytes,secreted into intercellular spaces,and binds to heparan sulfate proteoglycans(HSPG),and is dissociated under the action of heparin.It is captured and translocated into the blood by glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1(GPIHBP1)on endothelial cells of capillaries,hydro-lyzing the core triglycerides in lipoproteins in the blood,releasing free fatty acids for oxidation and utilization,or storage.LPL's enzy-matic activity is regulated by various interacting proteins,including ApoCs,ANGPTLs,LMF1,etc.Mutations in LPL-encoding gene,errors in protein synthesis and processing,or abnormalities in its interacting proteins can lead to LPL deficiency or dysfunction,cause clinical symptoms such as elevated blood lipids or pancreatitis,which seriously threatening the health of patients.At present,the routine clinical treatment for LPL deficiency related diseases is lipid-lowering drugs combined with strict dietary control,but the effect is not ideal.In recent years,drugs targeting LPL and its interacting protein genes have successively entered the stage of clinical research and marketing,and achieved good clinical effects.Among them,gene substitution,oligonucleotides,and small RNA drugs have been most concerned.Based on the characteristics of LPL and the pathologic mechanism of LPL deficiency(LPLD),the current therapeutic meth-ods and drug development progress were summarized in this review,so as to provide ideas for drug development and medical intervention of LPLD.
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