| Role of matrix Gla protein in angiotensin II-induced exacerbation of vascular calcification. | |
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MedLine Citation:
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PMID: 22796540 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Vascular calcification predicts an increased risk for cardiovascular events in atherosclerosis, diabetes, and end-stage kidney diseases. Matrix Gla protein (MGP), an inhibitor of calcification, limits calcium phosphate deposition in the vessel wall. There are many factors contributing to the progression of atherosclerosis, including hypertension, hyperlipidemia, the renin-angiotensin system, and inflammation. Angiotensin II (ANG II) plays a crucial role in the atherogenic process through not only its pressor responses but also its growth-promoting and inflammatory effects. In this study, we investigated the role of MGP in ANG II-induced exacerbation of vascular calcification in human vascular smooth muscle cells (VSMCs). The expression of MGP, calcification, and apoptosis in human VSMCs were examined by Western blot analysis, real-time PCR, in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, and enzyme-linked immunosorbent assay, respectively. Increase in VSMC calcification in human atherosclerotic plaques upregulates MGP expression and apoptosis in a negative feedback manner. ANG II inhibited MGP expression in VSMCs via and in vitro in a dose- and time-dependent manner through ANG II type 1 receptor and NF-κB signaling pathway. Meanwhile, MGP inhibited the calcification, caspase-3 activity, activation of runt-related transcription factor 2, and release of inflammatory cytokines by VSMCs induced by calcification medium (2.5 mM P(i)) and ANG II in vitro. These observations provide evidence that ANG II exacerbates vascular calcification through activation of the transcription factors, runt-related transcription factor 2 and NF-κB, and regulation of MGP, inflammatory cytokines expression in human VSMCs. |
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Authors:
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Guanghong Jia; Ryan M Stormont; Deepak M Gangahar; Devendra K Agrawal |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-07-13 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 303 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-09-03 Completed Date: 2012-11-07 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H523-32 Citation Subset: IM |
Affiliation:
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Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska 68178, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Angiotensin II / metabolism* Apoptosis Blotting, Western Calcium Phosphates / metabolism Calcium-Binding Proteins / genetics, metabolism* Carotid Arteries / metabolism, pathology Carotid Artery Diseases / genetics, immunology, metabolism*, pathology Caspase 3 / metabolism Cells, Cultured Core Binding Factor Alpha 1 Subunit / metabolism Cytokines / metabolism Enzyme Activation Enzyme-Linked Immunosorbent Assay Extracellular Matrix Proteins / genetics, metabolism* Feedback, Physiological Gene Expression Regulation Humans In Situ Nick-End Labeling Inflammation Mediators / metabolism Middle Aged Muscle, Smooth, Vascular / immunology, metabolism*, pathology Myocytes, Smooth Muscle / immunology, metabolism*, pathology NF-kappa B / metabolism Plaque, Atherosclerotic Real-Time Polymerase Chain Reaction Receptor, Angiotensin, Type 1 / metabolism Signal Transduction Time Factors Transfection Vascular Calcification / genetics, immunology, metabolism*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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R01-HL-090580/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/AGTR1 protein, human; 0/Calcium Phosphates; 0/Calcium-Binding Proteins; 0/Core Binding Factor Alpha 1 Subunit; 0/Cytokines; 0/Extracellular Matrix Proteins; 0/Inflammation Mediators; 0/NF-kappa B; 0/RUNX2 protein, human; 0/Receptor, Angiotensin, Type 1; 0/matrix Gla protein; 11128-99-7/Angiotensin II; 97Z1WI3NDX/calcium phosphate; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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