The Importance of Lipoprotein Lipase Regulation in Atherosclerosis

Aim. The goal of the study was to analyze the differential expression of lipid metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis.Material and Methods. The study was performed on the specimens of atherosclerotic plaques in 45–65-year-old patients with coronary atherosclerosis with stable exertional angina functional class II-IV without acute coronary syndrome. Coronary atherosclerosis was verified by coronary angiography. Atherosclerotic plaque tissue was sampled intraoperatively when indicated. Whole-genome sequencing of ribonucleic acid (RNA) was performed using the TruSeq RNA Sample Preparation Kit (Illumina, USA).Results. We analyzed the differences in the expression of 12 genes including LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, ABCA1, APOA1, APOE, LPL, SCARB1, and SREBF2 depending on the type of atherosclerotic plaques. The expression level of APOE gene was eight times higher in unstable atherosclerotic plaques of dystrophic-necrotic type (p < 0.0001). The expression levels of LDLR and APOB genes were eight times higher in stable atherosclerotic plaques (p < 0.0001). We did not find differences in the expression levels of the ABCG5, ABCG8, APOC3, CETP, CLPS, CYP7A1, and PNPLA5 genes.Conclusion. The study showed the differences in the activity of individual metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis. Obtained data may become the basis for the development of test systems aimed at predicting the development of atherosclerotic process and its complications.

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Section: Discussionunclassified

Analysis of differential expression of lipid metabolism genes in atherosclerotic plaques in patients with coronary atherosclerosis

Shakhtshneider

Ivanoshchuk

Ragino

et al. 2022

SJCEM

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“…LPL maintains TG homeostasis in blood and is the rate-limiting enzyme for the hydrolysis of TGs that are encapsulated in the core of TGRL particles ( Wang and Eckel, 2009 ; Tada et al, 2018 ; Kumari et al, 2021 ). It has been reported that gain-of-function and loss-of-function gene mutations of LPL lead to the imbalance of plasma TG levels, thereby influencing CVD events ( Rip et al, 2006 ; Wang and Eckel, 2009 ; Burnett et al, 2019 ).…”

Section: Emerging Targets For Lowering Triglyceridementioning

confidence: 99%

“…ANGPTL is a family of secreted glycoproteins consisting of eight members (ANGPTL1-8). These proteins, especially ANGPTL3, ANGPTL4, and ANGPTL8 are found to regulate the activity of LPL ( Li et al, 2020 ; Kumari et al, 2021 ). In the following, we mainly describe several intensively studied ANGPTL members that have potential applications for treatment of HTG.…”

Section: Emerging Targets For Lowering Triglyceridementioning

confidence: 99%

Triglyceride and Triglyceride-Rich Lipoproteins in Atherosclerosis

Zhang

Yin

Qiao

et al. 2022

Front. Mol. Biosci.

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Cardiovascular disease (CVD) is still the leading cause of death globally, and atherosclerosis is the main pathological basis of CVDs. Low-density lipoprotein cholesterol (LDL-C) is a strong causal factor of atherosclerosis. However, the first-line lipid-lowering drugs, statins, only reduce approximately 30% of the CVD risk. Of note, atherosclerotic CVD (ASCVD) cannot be eliminated in a great number of patients even their LDL-C levels meet the recommended clinical goals. Previously, whether the elevated plasma level of triglyceride is causally associated with ASCVD has been controversial. Recent genetic and epidemiological studies have demonstrated that triglyceride and triglyceride-rich lipoprotein (TGRL) are the main causal risk factors of the residual ASCVD. TGRLs and their metabolites can promote atherosclerosis via modulating inflammation, oxidative stress, and formation of foam cells. In this article, we will make a short review of TG and TGRL metabolism, display evidence of association between TG and ASCVD, summarize the atherogenic factors of TGRLs and their metabolites, and discuss the current findings and advances in TG-lowering therapies. This review provides information useful for the researchers in the field of CVD as well as for pharmacologists and clinicians.

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“…Unlike the contradictory data from the LPL activator, abrogating the inhibitory effects of ApoC3 and ANGPTLs on LPL activity consistently reduces circulating TG levels, thus yielding promising outcomes of dyslipidemia in different experimental animal models (4). Recently, ANGPTL3 and ApoC3 have been reported to be potential therapeutic targets for the treatment of HTG in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Targeting ApoC3 Paradoxically Aggravates Atherosclerosis in Hamsters With Severe Refractory Hypercholesterolemia

Guo

Zhang

et al. 2022

Front. Cardiovasc. Med.

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RationaleApoC3 plays a central role in the hydrolysis process of triglyceride (TG)-rich lipoproteins mediated by lipoprotein lipase (LPL), which levels are positively associated with the incidence of cardiovascular disease (CVD). Although targeting ApoC3 by antisense oligonucleotide (ASO), Volanesorsen markedly reduces plasma TG level and increase high-density lipoprotein cholesterol (HDL-C) in patients with hypertriglyceridemia (HTG), the cholesterol-lowering effect of ApoC3 inhibition and then the consequential outcome of atherosclerotic cardiovascular disease (ASCVD) have not been reported in patients of familial hypercholesterolemia (FH) with severe refractory hypercholesterolemia yet.ObjectiveTo investigate the precise effects of depleting ApoC3 on refractory hypercholesterolemia and atherosclerosis, we crossed ApoC3-deficient hamsters with a background of LDLR deficiency to generate a double knockout (DKO) hamster model (LDLR−/−, XApoC3−/−, DKO).Approach and ResultsOn the standard laboratory diet, DKO hamsters had reduced levels of plasma TG and total cholesterol (TC) relative to LDLR−/− hamsters. However, upon high-cholesterol/high-fat (HCHF) diet feeding for 12 weeks, ApoC3 deficiency reduced TG level only in female animals without affecting refractory cholesterol in the circulation, whereas apolipoprotein A1 (ApoA1) levels were significantly increased in DKO hamsters with both genders. Unexpectedly, loss of ApoC3 paradoxically accelerated diet-induced atherosclerotic development in female and male LDLR−/− hamsters but ameliorated fatty liver in female animals. Further analysis of blood biological parameters revealed that lacking ApoC3 resulted in abnormal platelet (PLT) indices, which could potentially contribute to atherosclerosis in LDLR−/− hamsters.ConclusionsIn this study, our novel findings provide new insight into the application of ApoC3 inhibition for severe refractory hypercholesterolemia and ASCVD.

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The Importance of Lipoprotein Lipase Regulation in Atherosclerosis

Cited by 45 publications

References 238 publications

Analysis of differential expression of lipid metabolism genes in atherosclerotic plaques in patients with coronary atherosclerosis

Analysis of differential expression of lipid metabolism genes in atherosclerotic plaques in patients with coronary atherosclerosis

Triglyceride and Triglyceride-Rich Lipoproteins in Atherosclerosis

Targeting ApoC3 Paradoxically Aggravates Atherosclerosis in Hamsters With Severe Refractory Hypercholesterolemia

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