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Relationship between Procalcitonin (PCT) and High-Density Lipoprotein (HDL) in bacterial sepsis
Published in Cut Adeya Adella, Stem Cell Oncology, 2018
D. Tarigan, T. Kembaren, A. Rahimi
Khovidhunkit et al. (2014) found a change in other protein content associated with HDL (Serum paraoxonase (PON1), Platelet-activating Factor Acetylhydrolase (PAF-AH)), resulting in a decrease in antioxidant properties from HDL and enhanced pro-atherogenic lipid content (Cao et al., 1998). Endotoxemia also induces enhancement of some enzymes involved in HDL remodelling, including endothelial lipase [10] and secretory phospholipase A2 and other decreases such as Cholesteryl Protein Transfer Ester (CETP) and Lecithin-Cholesterol Acyltransferase (LCAT) which will eventually decrease the functional properties of HDL (Delaliera et al., 2012).
Placental origins of diabesity and the origin of preeclampsia
Published in Moshe Hod, Lois G. Jovanovic, Gian Carlo Di Renzo, Alberto de Leiva, Oded Langer, Textbook of Diabetes and Pregnancy, 2018
Gernot Desoye, Berthold Huppertz
Endothelial lipase (EL), a close relative of lipoprotein lipase (LPL), was recently identified on the microvillous syncytiotrophoblast membrane at the end of gestation (Figure 13.1), whereas LPL was found in cells subjacent to the fetoplacental endothelium.54 EL is upregulated in placentas from obese women with GDM, but unchanged in placentas from lean GDM cases.55 This suggests that metabolic inflammation together with diabetic conditions accounted for dysregulation of EL in pregnancies complicated by obesity and GDM. TNF-α and leptin, both inflammatory cytokines often elevated in diabesity, are putative key regulators of EL.
Lipoprotein Metabolism and Implications for Atherosclerosis Risk Determination and Treatment Decisions
Published in P. K. Shah, Risk Factors in Coronary Artery Disease, 2006
H. Robert Superko, Szilard Voros, Spencer King III
Five major enzymes play a role in basic lipid metabolism: LPL, HL, endothelial lipase (EL), LCAT, and acyl-CoA:cholesterol acyltransferase (ACAT) (Table 1). LPL is a lipolytic enzyme located on the surface of vascular endothelial cells and macrophages (35). It is responsible for Triglycerides hydrolysis. Hepatic lipase (HL) is an enzyme synthesized by hepatocytes and binds to endothelial cells, allowing it to interact with lipoproteins as they traverse the liver (36). Endothelial lipase (EL) is a lipolytic enzyme that uses phospholipids as the substrate (37). LCAT is responsible for the esterification of cholesterol molecules in HDL (38). ACAT serves to convert free cholesterol to esterified cholesterol intracellularly.
Evinacumab for the treatment of homozygous familial hypercholesterolemia
Published in Expert Review of Clinical Pharmacology, 2022
Yanli Gao, Baoqi Zhang, Junyi Yang
ANGPTL3 is a member of the angiopoietin-like protein family expressed primarily in the liver [10,31–33]. Lipoprotein lipase (LPL) and endothelial lipase (EL) regulate metabolism of triglyceride (TG) and very low-density lipoprotein (VLDL, the upstream production of LDL). ANGPTL3 can inhibit the activity of LPL and EL, and in turn leads to raising plasma concentrations of TG and LDL-C [34–36]. Loss-of-function mutations in ANGPTL3 lead to decreasing plasma levels of TG, LDL-C, and HDL-C [37]. The mechanism of LDL-C reduction via inhibition of ANGPTL3 is independent of the LDL receptors, so it represents a promising therapeutic approach for patients with HoFH [38]. Evinacumab is a fully human monoclonal antibody that binds to and inhibits ANGPTL3, and it can reduce the level of TG, LDL-C, and HDL-C. Evinacumab has high affinity and an obvious effect on ANGPTL3 (in human, murine, rat and monkey the KD was 0.26 to 1.28 nmol/L, IC50 was 1.0 to 13.6 nmol/L). In mice and humans evinacumab was associated with dose-dependent reduction in LDL-C and TG levels [39,40]. In dyslipidemic mice, inhibition of ANGPTL3 with evinacumab resulted in a decrease in the atherosclerotic lesion area [40,41].
Emerging lipid lowering agents targeting LDL cholesterol
Published in Postgraduate Medicine, 2020
The exact role of the ANGPTL3 protein in lipid metabolism is not yet fully clarified. It inhibits lipoprotein lipase and endothelial lipase activity, increasing levels of triglycerides and other lipids. Moreover, it may have proinflammatory, proangiogenic effects and a negative effect on cholesterol efflux, implying additional proatherosclerotic properties. Familial combined hypolipidemia is caused by homozygous loss of function ANGPTL3 mutations. It is associated with overall decrease in lipid levels including LDL-C, HDL-C, and triglycerides as well as reduced ASCVD risk [52]. Even heterozygous carriers of loss of function ANGPTL3 variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing ASCVD, as compared to non-carriers [53]. In the DiscovEHR study, which involved ANGTPL3 gene sequencing of 58,335 participants, loss-of-function variants in ANGPTL3 were associated with significantly lower serum levels of triglycerides, HDL-C, and LDL-C. The loss of function heterozygosity was found in 0.33% of patients with coronary artery disease and in 0.45% of controls (adjusted odds ratio, 0.59; 95% confidence interval, 0.41 to 0.85; P = 0.004) [54].
ANGPTL3: a novel biomarker and promising therapeutic target
Published in Journal of Drug Targeting, 2019
Shuang Jiang, Guo-Hui Qiu, Neng Zhu, Zhe-Yu Hu, Duan-Fang Liao, Li Qin
Angiopoietin-like protein 3 (ANGPTL3), also known as angiopoietin-5, first discovered in 1999 is closely related to the disorder of lipid metabolism. The encoded ANGPTL3 protein belongs to a kind of secreted protein factors with multiple functions such as the promotion of neovascularisation and hyperlipidaemia. Generally, Human ANGPTL3 is a 460-amino-acid polypeptide (molecular mass of 70 kDa) with the characteristic structure of angiopoietins. ANGPTL3 gene is located on human chromosome 1 (1p31.1–p22.3) and includes seven exons and six introns. Unlike human ANGPTL3, the murine ANGPTL3 is a 455-acid polypeptide, which is encoded by seven exons on mouse chromosome 4. Both human and murine ANGPTL3 is mainly expressed in the liver but rarely expressed in other tissues and organs [1,2]. The major functions of ANGPTL3 are involved in regulating lipid metabolism and inducing angiogenesis [3,4]. Particularly, it plays a key role in regulating circulating triglycerides (TG) and cholesterol levels through inhibition of lipoprotein lipase (LPL) and endothelial lipase (EL) enzymes activity [4].