Lysyl oxidase-like 2 depletion is protective in age-associated vascular stiffening.
Age Factors
Amino Acid Oxidoreductases
/ deficiency
Animals
Aorta, Thoracic
/ enzymology
Aortic Diseases
/ enzymology
Cells, Cultured
Coculture Techniques
Endothelial Cells
/ metabolism
Extracellular Matrix
/ metabolism
Female
Humans
Male
Mice, Knockout
Muscle, Smooth, Vascular
/ enzymology
Myocytes, Smooth Muscle
/ enzymology
Nitric Oxide
/ metabolism
Paracrine Communication
Signal Transduction
Vascular Remodeling
Vascular Stiffness
Vasoconstriction
aging
lysyl oxidase-like 2
pulse-wave velocity
vascular stiffness
Journal
American journal of physiology. Heart and circulatory physiology
ISSN: 1522-1539
Titre abrégé: Am J Physiol Heart Circ Physiol
Pays: United States
ID NLM: 100901228
Informations de publication
Date de publication:
01 07 2019
01 07 2019
Historique:
pubmed:
20
4
2019
medline:
24
3
2020
entrez:
20
4
2019
Statut:
ppublish
Résumé
Vascular stiffening and its sequelae are major causes of morbidity and mortality in the elderly. The increasingly accepted concept of "smooth muscle cell (SMC) stiffness syndrome" along with matrix deposition has emerged in vascular biology to account for the mechanical phenotype of arterial aging, but the molecular targets remain elusive. In this study, using an unbiased proteomic analysis, we identified lysyl oxidase-like 2 (LOXL2) as a critical SMC mediator for age-associated vascular stiffening. We tested the hypothesis that loss of LOXL2 function is protective in aging-associated vascular stiffening. We determined that exogenous and endogenous nitric oxide markedly decreased LOXL2 abundance and activity in the extracellular matrix of isolated SMCs and LOXL2 endothelial cells suppress LOXL2 abundance in the aorta. In a longitudinal study, LOXL2
Identifiants
pubmed: 31002285
doi: 10.1152/ajpheart.00670.2018
pmc: PMC6692735
doi:
Substances chimiques
Nitric Oxide
31C4KY9ESH
Amino Acid Oxidoreductases
EC 1.4.-
LOXL2 protein, human
EC 1.4.3.-
Loxl2 protein, mouse
EC 1.4.3.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
H49-H59Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL145132
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105296
Pays : United States
Commentaires et corrections
Type : CommentIn
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