| First Author | Antoniak S | Year | 2017 |
| Journal | Cardiology | Volume | 136 |
| Issue | 4 | Pages | 258-268 |
| PubMed ID | 27880950 | Mgi Jnum | J:345008 |
| Mgi Id | MGI:6756903 | Doi | 10.1159/000452269 |
| Citation | Antoniak S, et al. (2017) Protease-Activated Receptor 1 Contributes to Angiotensin II-Induced Cardiovascular Remodeling and Inflammation. Cardiology 136(4):258-268 |
| abstractText | BACKGROUND: Angiotensin II (Ang II) plays an important role in cardiovascular disease. It also leads to the activation of coagulation. The coagulation protease thrombin induces cellular responses by activating protease-activated receptor 1 (PAR-1). We investigated whether PAR-1 contributes to Ang II-induced cardiovascular remodeling and inflammation. METHODS AND RESULTS: PAR-1+/+ (wild-type; WT) and PAR-1-/- mice were infused with Ang II (600 ng/kg/min) for up to 4 weeks. In WT mice, this dose of Ang II did not cause a significant increase in blood pressure but it did cause pathological changes in both the aorta and the heart. Ang II infusion resulted in vascular remodeling of the aorta, demonstrated by a significant increase in medial wall thickening and perivascular fibrosis. Importantly, both parameters were significantly attenuated by PAR-1 deficiency. Furthermore, perivascular fibrosis around coronary vessels was reduced in Ang II-treated PAR-1-/- mice compared to WT mice. In addition, PAR-1 deficiency significantly attenuated Ang II induction of inflammatory cytokines and profibrotic genes in the aortas compared to WT mice. Finally, PAR-1 deficiency had no effect on Ang II-induced heart hypertrophy. However, the heart function measured by fractional shortening was less impaired in PAR-1-/- mice than in WT mice. CONCLUSION: Our data indicate that PAR-1 plays a significant role in cardiovascular remodeling mediated by a blood pressure-independent action of Ang II. |
