Journal
CIRCULATION RESEARCH
Volume 106, Issue 3, Pages 611-U108Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.109.212837
Keywords
angiotensin II; hypertrophy; hyperplasia; p47(phox); Id3
Funding
- NIH [HL80100]
- American Heart Association Ohio Valley Affiliate Predoctoral Fellowship [0615222B]
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Rationale: Angiotensin II (Ang II) has diverse effects on smooth muscle cells (SMCs). The diversity of effects may relate to the regional location of this cell type. Objective: The aim of this study was to define whether Ang II exerted divergent effects on smooth muscle cells in the aorta and determine the role of blood pressure and specific oxidant mechanisms. Methods and Results: Ang II (1000 ng/kg per minute) infusion for 28 days into mice increased systolic blood pressure and promoted medial expansion of equivalent magnitude throughout the entire aorta. Both effects were ablated by angiotensin II type 1a (AT(1a)) receptor deficiency. Similar increases in systolic blood pressure by administration of norepinephrine promoted no changes in aortic medial thickness. Increased medial thickness was attributable to SMC expansion owing to hypertrophy in most aortic regions, with the exception of hyperplasia of the ascending aorta. Deficiency of the p47(phox) component of NADPH oxidase ablated Ang II-induced medial expansion in all aortic regions. Analysis of mRNA and protein throughout the aorta revealed a much higher abundance of the inhibitor of differentiation 3 (Id3) in the ascending aorta compared to all other regions. A functional role was demonstrated by Id3 deficiency inhibiting Ang II-induced SMC hyperplasia of the ascending aorta. Conclusions: In conclusion, Ang II promotes both aortic medial hypertrophy and hyperplasia in a region-specific manner via an oxidant mechanism. The ascending aortic hyperplasia is dependent on Id3. (Circ Res. 2010;106:611-619.)
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