Aspirin downregulates angiotensin type 1 receptor transcription implications in capillary formation from endothelial cells

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 (p22, p47, p67, 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.