Local Pressure Drives Low-Density Lipoprotein Accumulation and Coronary Atherosclerosis in Hypertensive Minipigs.
atherosclerosis
coronary artery disease
hypertension
low-density lipoproteins
minipigs
proteome
Journal
Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365
Informations de publication
Date de publication:
09 02 2021
09 02 2021
Historique:
received:
03
09
2020
revised:
12
11
2020
accepted:
22
11
2020
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
7
9
2021
Statut:
ppublish
Résumé
The mechanisms by which hypertension accelerates coronary artery disease are poorly understood. Patients with hypertension often have confounding humoral changes, and to date, no experimental models have allowed analysis of the isolated effect of pressure on atherosclerosis in a setting that recapitulates the dimensions and biomechanics of human coronary arteries. This study sought to analyze the effect of pressure on coronary atherosclerosis and explore the underlying mechanisms. Using inflatable suprarenal aortic cuffs, we increased mean arterial pressure by >30 mm Hg in the cephalad body part of wild-type and hypercholesterolemic proprotein convertase subtilisin kexin type 9 (PCSK9) Under hypercholesterolemic conditions in PCSK9 Increased pressure per se facilitates coronary atherosclerosis. Our data indicate that restructuring of the artery to match increased tensile forces in hypertension alters the passage of macromolecules and leads to increased intimal accumulation of low-density lipoproteins.
Sections du résumé
BACKGROUND
The mechanisms by which hypertension accelerates coronary artery disease are poorly understood. Patients with hypertension often have confounding humoral changes, and to date, no experimental models have allowed analysis of the isolated effect of pressure on atherosclerosis in a setting that recapitulates the dimensions and biomechanics of human coronary arteries.
OBJECTIVES
This study sought to analyze the effect of pressure on coronary atherosclerosis and explore the underlying mechanisms.
METHODS
Using inflatable suprarenal aortic cuffs, we increased mean arterial pressure by >30 mm Hg in the cephalad body part of wild-type and hypercholesterolemic proprotein convertase subtilisin kexin type 9 (PCSK9)
RESULTS
Under hypercholesterolemic conditions in PCSK9
CONCLUSIONS
Increased pressure per se facilitates coronary atherosclerosis. Our data indicate that restructuring of the artery to match increased tensile forces in hypertension alters the passage of macromolecules and leads to increased intimal accumulation of low-density lipoproteins.
Identifiants
pubmed: 33538256
pii: S0735-1097(20)38002-5
doi: 10.1016/j.jacc.2020.11.059
pii:
doi:
Substances chimiques
Biomarkers
0
Lipoproteins, LDL
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
575-589Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Funding Support And Author Disclosures This work was supported by grants from the Danish Heart Foundation Independent Research Funding Denmark and the Ministerio de Economia, Industria y Competividad with cofunding from the Fondo Europeo de Desarrollo Regional (SAF2016-75580-R and PGC2018-097019-B-I00), the Carlos III Institute of Health-Fondo de Investigación Sanitaria (IPT17/0019–ISCIII-SGEFI/ERDF, ProteoRed), the Fundació la Marató de TV3 (grant 122/C/2015) and “la Caixa” Banking Foundation (project code HR17-00247). The CNIC is supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia e Innovación, and the Pro Centro Nacional de Investigaciones Cardiovasculares Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.