An octimibate derivative, Oxa17, enhances cholesterol efflux and exerts anti-inflammatory and atheroprotective effects in experimental atherosclerosis.


Journal

Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032

Informations de publication

Date de publication:
06 2021
Historique:
received: 25 01 2021
revised: 19 04 2021
accepted: 21 04 2021
pubmed: 26 4 2021
medline: 15 9 2021
entrez: 25 4 2021
Statut: ppublish

Résumé

Atherosclerotic cardiovascular diseases (ASCVDs), associated with vascular inflammation and lipid dysregulation, are responsible for high morbidity and mortality rates globally. For ASCVD treatment, cholesterol efflux plays an atheroprotective role in ameliorating inflammation and lipid dysregulation. To develop a multidisciplinary agent for promoting cholesterol efflux, octimibate derivatives were screened and investigated for the expression of ATP-binding cassette transporter A1 (ABCA1). Western blotting and qPCR analysis were conducted to determine the molecular mechanism associated with ABCA1 expression in THP-1 macrophages; results revealed that Oxa17, an octimibate derivative, enhanced ABCA1 expression through liver X receptors alpha (LXRα) activation but not through the microRNA pathway. We also investigated the role of Oxa17 in high-fat diet (HFD)-fed mice used as an in vivo atherosclerosis-prone model. In ldlr

Identifiants

pubmed: 33895158
pii: S0006-2952(21)00187-8
doi: 10.1016/j.bcp.2021.114581
pii:
doi:

Substances chimiques

Anti-Inflammatory Agents 0
Imidazoles 0
Cholesterol 97C5T2UQ7J
octimibate S0SIQ441YZ

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

114581

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Auteurs

Pi-Fen Tsui (PF)

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.

Ching-Yuh Chern (CY)

Department of Applied Chemistry, National Chiayi University, Chiayi City 60004, Taiwan.

Chih-Feng Lien (CF)

Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.

Feng-Yen Lin (FY)

Taipei Heart Research Institute and Departments of Internal Medicine, Taipei Medical University, Taipei 11031, Taiwan; Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan.

Chien-Sung Tsai (CS)

Division of Cardiovascular Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; Department and Graduate Institute of Pharmacology, National Defense Medical Center, Taipei 11490, Taiwan; Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russia.

Min-Chien Tsai (MC)

Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei 11490, Taiwan.

Chin-Sheng Lin (CS)

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan. Electronic address: doc10446@mail.ndmctsgh.edu.tw.

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Classifications MeSH