Document Detail

Role of matrix Gla protein in angiotensin II-induced exacerbation of vascular calcification.
MedLine Citation:
PMID:  22796540     Owner:  NLM     Status:  MEDLINE    
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.
Guanghong Jia; Ryan M Stormont; Deepak M Gangahar; Devendra K Agrawal
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-13
Journal Detail:
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:
Created Date:  2012-09-03     Completed Date:  2012-11-07     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H523-32     Citation Subset:  IM    
Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Angiotensin II / metabolism*
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
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
Vascular Calcification / genetics,  immunology,  metabolism*,  pathology
Grant Support
Reg. No./Substance:
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

Previous Document:  Mapping cardiac surface mechanics with structured light imaging.
Next Document:  Tertiary Centres have improved Survival compared to other Hospitals in the Copenhagen Area after Out...