High-Density Lipoprotein Function, Dysfunction, and Reverse Cholesterol Transport
TL;DR: Test of HDL function, which have not yet been developed as routine diagnostic assays, may prove useful and be a better predictor of cardiovascular risk than HDL-cholesterol levels.
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Abstract: Although high high-density lipoprotein (HDL)-cholesterol levels are associated with decreased cardiovascular risk in epidemiological studies, recent genetic and pharmacological findings have raised doubts about the beneficial effects of HDL. Raising HDL levels in animal models by infusion or overexpression of apolipoprotein A-I has shown clear vascular improvements, such as delayed atherosclerotic lesion progression and accelerated lesion regression, along with increased reverse cholesterol transport. Inflammation and other factors, such as myeloperoxidase-mediated oxidation, can impair HDL production and HDL function, with regard to its reverse cholesterol transport, antioxidant, and anti-inflammatory activities. Thus, tests of HDL function, which have not yet been developed as routine diagnostic assays, may prove useful and be a better predictor of cardiovascular risk than HDL-cholesterol levels.
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Citations
Dysfunctional HDL and atherosclerotic cardiovascular disease
Robert S. Rosenson,H. Bryan Brewer,Benjamin J. Ansell,Philip J. Barter,M. John Chapman,Jay W. Heinecke,Anatol Kontush,Alan R. Tall,Nancy R. Webb +8 more
TL;DR: The proinflammatory enzyme myeloperoxidase induces both oxidative modification and nitrosylation of specific residues on plasma and arterial apolipoprotein A-I to render HDL dysfunctional, which results in impaired ABCA1 macrophage transport, the activation of inflammatory pathways, and an increased risk of coronary artery disease.
HDL and Reverse Cholesterol Transport.
TL;DR: On balance, the evidence still argues for further research to better understand how HDL functionality contributes to RCT to develop prevention and treatment strategies to reduce the risk of cardiovascular disease.
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Pathophysiology of Atherosclerosis
Shifa Jebari-Benslaiman,Unai Galicia-Garcia,Asier Larrea-Sebal,Javier Rekondo Olaetxea,Iraide Alloza,Koen Vandenbroeck,Asier Benito-Vicente,César Martín +7 more
TL;DR: The post-transcriptional regulation and modulation of atheroma plaque by microRNAs and lncRNAs, the role of microbiota, and the importance of sex as a crucial risk factor in atherosclerosis are covered here in order to provide a global view of the disease.
The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases.
J. Mark Brown,Stanley L. Hazen +1 more
TL;DR: The opportunities and challenges that lie ahead in targeting meta-organismal endocrinology for CVD prevention are discussed and pharmacological interventions at the level of the gut microbial endocrine organ are discussed.
An abundant dysfunctional apolipoprotein A1 in human atheroma
Ying Huang,Joseph A. DiDonato,Bruce S. Levison,Dave Schmitt,Lin Li,Yuping Wu,Jennifer A. Buffa,Timothy Kim,Gary Gerstenecker,Gary Gerstenecker,Xiaodong Gu,Chandra S Kadiyala,Zeneng Wang,Miranda K. Culley,Jennie E. Hazen,Anthony J. DiDonato,Xiaoming Fu,Stela Z Berisha,Dao-Quan Peng,Truc Nguyen,Shaohong Liang,Chia-Chi Chuang,Leslie Cho,Edward F. Plow,Paul L. Fox,Valentin Gogonea,Valentin Gogonea,W.H. Wilson Tang,John S. Parks,Edward A. Fisher,Jonathan D. Smith,Stanley L. Hazen +31 more
TL;DR: A high-affinity monoclonal antibody is developed that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl− system and demonstrates both a potent proinflammatory activity on endothelial cells and an impaired HDL biogenesis activity in vivo.
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