Plasma HDL pattern, cholesterol efflux and cholesterol loading capacity of serum in carriers of a novel missense variant (Gly176Trp) of endothelial lipase

Pisciotta, Livia; Ossoli, Alice; Ronca, Annalisa; Garuti, Anna; Fresa, Raffaele; Favari, Elda; Calabresi, Laura; Calandra, Sebastiano; Bertolini, Stefano

doi:10.1016/j.jacl.2022.08.002

Cited by 4 publications

(1 citation statement)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, plasma HDL cholesterol levels are decreased in endothelial lipase overexpressing mice [ 96 , 97 ]. In humans, deleterious variants in the LIPG gene, encoding endothelial lipase, are associated with increased plasma HDL cholesterol levels [ 98 , 99 , 100 ].…”

Section: Pcsk6 and Cardiovascular Pathophysiologymentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease

Chen

2022

IJMS

View full text Add to dashboard Cite

Proprotein convertase subtilisin/kexin 6 (PCSK6) is a secreted serine protease expressed in most major organs, where it cleaves a wide range of growth factors, signaling molecules, peptide hormones, proteolytic enzymes, and adhesion proteins. Studies in Pcsk6-deficient mice have demonstrated the importance of Pcsk6 in embryonic development, body axis specification, ovarian function, and extracellular matrix remodeling in articular cartilage. In the cardiovascular system, PCSK6 acts as a key modulator in heart formation, lipoprotein metabolism, body fluid homeostasis, cardiac repair, and vascular remodeling. To date, dysregulated PCSK6 expression or function has been implicated in major cardiovascular diseases, including atrial septal defects, hypertension, atherosclerosis, myocardial infarction, and cardiac aging. In this review, we describe biochemical characteristics and posttranslational modifications of PCSK6. Moreover, we discuss the role of PCSK6 and related molecular mechanisms in cardiovascular biology and disease.

show abstract

Section: Pcsk6 and Cardiovascular Pathophysiologymentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease

Chen

2022

IJMS

View full text Add to dashboard Cite

show abstract

Association of the PCSK6 rs1531817(C/A) polymorphism with the prognosis and coronary stenosis in premature myocardial infarction patients: a prospective cohort study

Sun,

Wang,

et al. 2024

Lipids Health Dis

View full text Add to dashboard Cite

Background Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. Methods This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. Results 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. Conclusion Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.

show abstract

Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism

Hur,

Yang,

Kim

et al. 2023

Front. Nutr.

View full text Add to dashboard Cite

IntroductionHypo-high-density lipoprotein cholesterolemia (hypo-HDL-C) contributes to the development of cardiovascular diseases. The hypothesis that the polygenic variants associated with hypo-HDL-C interact with lifestyle factors was examined in 58,701 middle-aged Korean adults who participated in the Korean Genome and Epidemiology Study (KoGES).MethodsParticipants were categorized into the Low-HDL (case; n = 16,980) and Normal-HDL (n = 41,721) groups. The participants in the Low-HDL group were selected using the guideline-based cutoffs for hypo-HDL-C (<40 mg/dL for men and < 50 mg/dL for women) and included those taking medication for dyslipidemia. The genes associated with hypo-HDL-C were determined through a genome-wide association study (GWAS) in a city hospital-based cohort, and the results were validated in the Ansan/Anung study. The genetic variants for the single nucleotide polymorphism (SNP)-SNP interaction were selected using a generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS) generated was evaluated for interaction with lifestyle parameters.ResultsThe participants with hypo-HDL-C showed a 1.45 and 1.36-fold higher association with myocardial infarction and stroke, respectively. The High-PRS with four SNPs, namely ZPR1_rs3741297, CETP_rs708272, BUD13_rs180327, and ALDH1A2_rs588136, and that with the 11q23.3 haplotype were positively associated with hypo-HDL-C by about 3 times, which was a 2.4-fold higher association than the PRS of 24 SNP with p < 5×10−8. The risk alleles of CETP_rs708272 and ALDH1A2_rs588136 were linked to increased expression in the heart and decreased in the brain, respectively. The selected SNPs were linked to the reverse cholesterol transport pathway, triglyceride-rich lipoprotein particle remodeling pathway, cholesterol storage, and macrophage-derived foam cell differentiation regulation. The PRS of the 4-SNP model interacted with energy intake and smoking status, while that of the haplotype interacted with a glycemic index of the diet, sulfur microbial diet, and smoking status.DiscussionAdults with a genetic risk for hypo-HDL-C need to modulate their diet and smoking status to reduce their risk.

show abstract

Plasma HDL pattern, cholesterol efflux and cholesterol loading capacity of serum in carriers of a novel missense variant (Gly176Trp) of endothelial lipase

Cited by 4 publications

References 34 publications

Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease

Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease

Association of the PCSK6 rs1531817(C/A) polymorphism with the prognosis and coronary stenosis in premature myocardial infarction patients: a prospective cohort study

Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism

Contact Info

Product

Resources

About