Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0002612
Title: Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease
Authors: Rodriguez-Feo J.A.
Hellings W.E.
Moll F.L.
De Vries J.-P.P.M.
van Middelaar B.J.
Alegra A.
Sluijter J.
van der Broek T.
Sessa W.C.
De Kleijn D.P.V. 
Pasterkamp G.
Keywords: acetylsalicylic acid
beta adrenergic receptor blocking agent
caveolin 1
cyclooxygenase 2
dipeptidyl carboxypeptidase inhibitor
gelatinase B
high density lipoprotein cholesterol
hydroxymethylglutaryl coenzyme A reductase inhibitor
interleukin 6
interleukin 8
lipopolysaccharide
low density lipoprotein cholesterol
nonsteroid antiinflammatory agent
triacylglycerol
caveolin 1
gelatinase B
interleukin 6
interleukin 8
adult
aged
animal experiment
animal model
animal tissue
artery injury
artery intima proliferation
article
atherosclerosis
atherosclerotic plaque
cardiovascular disease
carotid artery obstruction
carotid endarterectomy
cholesterol blood level
controlled study
down regulation
enzyme activity
female
follow up
heart infarction
human
human tissue
incidence
macrophage
major clinical study
male
mouse
nonhuman
prognosis
protein expression
protein localization
restenosis
sex difference
swine
thrombosis
Western blotting
animal
atherosclerosis
carotid artery disease
genetics
immunohistochemistry
immunology
metabolism
Mus
Sus
Aged
Animals
Atherosclerosis
Carotid Artery Diseases
Caveolin 1
Follow-Up Studies
Humans
Immunohistochemistry
Interleukin-6
Interleukin-8
Male
Matrix Metalloproteinase 9
Mice
Issue Date: 2008
Publisher: Public Library of Science
Citation: Rodriguez-Feo J.A., Hellings W.E., Moll F.L., De Vries J.-P.P.M., van Middelaar B.J., Alegra A., Sluijter J., van der Broek T., Sessa W.C., De Kleijn D.P.V., Pasterkamp G. (2008). Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease. PLoS ONE 3 (7) : e2612. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0002612
Abstract: Caveolin-1 (Cav-1) is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease. We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin) reduced gelatinase. activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice. This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of-Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target in the prevention of human atherosclerotic disease and the loss of Cav-1 may be a novel biomarker of vulnerable plaque with prognostic value. © 2008 Rodriguez-Feo et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/165607
ISSN: 19326203
DOI: 10.1371/journal.pone.0002612
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