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Aspirin Downregulates Angiotensin Type 1 Receptor Transcription Implications in Capillary Formation From Endothelial Cells

Mitra, Sona MD; Wang, Xianwei MD, PhD; Khaidakov, Magomed MD, PhD; Ding, Zufeng PhD; Ayyadevera, Srinivas PhD; Hearnsberger, Emily MS; Goyal, Tanu MD; Mehta, Jawahar L. MD, PhD

Journal of Cardiovascular Pharmacology: August 2012 - Volume 60 - Issue 2 - p 187–192
doi: 10.1097/FJC.0b013e31825b61e2
Original Article

Abstract: Aspirin [acetyl salicylic acid (ASA)] inhibits nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species generation, a pathway that underlies formation of new capillaries (angiogenesis). Angiotensin II (Ang II) participates in angiogenesis by activating type 1 receptor (AT1R). We examined if ASA would inhibit AT1R transcription, which requires NADPH oxidase, and thereby new capillary formation. Human umbilical vein endothelial cells were cultured in Matrigel and treated with Ang II with and without ASA. Expression of AT1R and NADPH oxidase was measured by quantitative polymerase chain reaction. Ang II in low concentrations induced AT1R messenger RNA and new capillary formation. ASA and its salicylic acid (SA) moiety both suppressed Ang II-mediated AT1R and vascular endothelial growth factor expression and the subsequent new capillary formation. Of note, the AT1R blocker losartan prevented new capillary formation. ASA and SA also suppressed NADPH oxidase (p22phox, p47phox, p67phox, and gp91 messenger RNA) expression. These observations suggest that ASA can inhibit Ang II–induced capillary formation in part via blocking NADPH oxidase and AT1R transcription. Because SA moiety had similar effect as ASA on AT1R expression, we suggest that the effect of ASA on new capillary formation is mediated by its SA moiety.

Division of Cardiology, The Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, AR.

Reprints: Jawahar L. Mehta, MD, PhD, Cardiovascular Division, University of Arkansas for Medical Sciences, Little Rock, AR 72212 (e-mail:

Supported in part by funds from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, Washington, DC, and a grant from Bayer-Schering Pharma.

The authors report no conflicts of interest.

Drs. Mitra and Wang contributed equally to this manuscript.

The contents of this article do not represent the views of the Department of Veterans Affairs or the US Government.

Received January 27, 2012

Accepted April 19, 2012

© 2012 Lippincott Williams & Wilkins, Inc.