Please use this identifier to cite or link to this item:
https://doi.org/10.1371/journal.pone.0002612
DC Field | Value | |
---|---|---|
dc.title | Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease | |
dc.contributor.author | Rodriguez-Feo J.A. | |
dc.contributor.author | Hellings W.E. | |
dc.contributor.author | Moll F.L. | |
dc.contributor.author | De Vries J.-P.P.M. | |
dc.contributor.author | van Middelaar B.J. | |
dc.contributor.author | Alegra A. | |
dc.contributor.author | Sluijter J. | |
dc.contributor.author | van der Broek T. | |
dc.contributor.author | Sessa W.C. | |
dc.contributor.author | De Kleijn D.P.V. | |
dc.contributor.author | Pasterkamp G. | |
dc.date.accessioned | 2020-03-18T05:52:40Z | |
dc.date.available | 2020-03-18T05:52:40Z | |
dc.date.issued | 2008 | |
dc.identifier.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 | |
dc.identifier.issn | 19326203 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/165607 | |
dc.description.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. | |
dc.publisher | Public Library of Science | |
dc.source | Unpaywall 20200320 | |
dc.subject | acetylsalicylic acid | |
dc.subject | beta adrenergic receptor blocking agent | |
dc.subject | caveolin 1 | |
dc.subject | cyclooxygenase 2 | |
dc.subject | dipeptidyl carboxypeptidase inhibitor | |
dc.subject | gelatinase B | |
dc.subject | high density lipoprotein cholesterol | |
dc.subject | hydroxymethylglutaryl coenzyme A reductase inhibitor | |
dc.subject | interleukin 6 | |
dc.subject | interleukin 8 | |
dc.subject | lipopolysaccharide | |
dc.subject | low density lipoprotein cholesterol | |
dc.subject | nonsteroid antiinflammatory agent | |
dc.subject | triacylglycerol | |
dc.subject | caveolin 1 | |
dc.subject | gelatinase B | |
dc.subject | interleukin 6 | |
dc.subject | interleukin 8 | |
dc.subject | adult | |
dc.subject | aged | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | artery injury | |
dc.subject | artery intima proliferation | |
dc.subject | article | |
dc.subject | atherosclerosis | |
dc.subject | atherosclerotic plaque | |
dc.subject | cardiovascular disease | |
dc.subject | carotid artery obstruction | |
dc.subject | carotid endarterectomy | |
dc.subject | cholesterol blood level | |
dc.subject | controlled study | |
dc.subject | down regulation | |
dc.subject | enzyme activity | |
dc.subject | female | |
dc.subject | follow up | |
dc.subject | heart infarction | |
dc.subject | human | |
dc.subject | human tissue | |
dc.subject | incidence | |
dc.subject | macrophage | |
dc.subject | major clinical study | |
dc.subject | male | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | prognosis | |
dc.subject | protein expression | |
dc.subject | protein localization | |
dc.subject | restenosis | |
dc.subject | sex difference | |
dc.subject | swine | |
dc.subject | thrombosis | |
dc.subject | Western blotting | |
dc.subject | animal | |
dc.subject | atherosclerosis | |
dc.subject | carotid artery disease | |
dc.subject | genetics | |
dc.subject | immunohistochemistry | |
dc.subject | immunology | |
dc.subject | metabolism | |
dc.subject | Mus | |
dc.subject | Sus | |
dc.subject | Aged | |
dc.subject | Animals | |
dc.subject | Atherosclerosis | |
dc.subject | Carotid Artery Diseases | |
dc.subject | Caveolin 1 | |
dc.subject | Follow-Up Studies | |
dc.subject | Humans | |
dc.subject | Immunohistochemistry | |
dc.subject | Interleukin-6 | |
dc.subject | Interleukin-8 | |
dc.subject | Male | |
dc.subject | Matrix Metalloproteinase 9 | |
dc.subject | Mice | |
dc.type | Article | |
dc.contributor.department | SURGERY | |
dc.description.doi | 10.1371/journal.pone.0002612 | |
dc.description.sourcetitle | PLoS ONE | |
dc.description.volume | 3 | |
dc.description.issue | 7 | |
dc.description.page | e2612 | |
dc.published.state | Published | |
Appears in Collections: | Elements Staff Publications |
Show simple item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_1371_journal_pone_0002612.pdf | 534.86 kB | Adobe PDF | OPEN | None | View/Download |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.