%0 Figure %A S., Antoniak %A J.C., Cardenas %A L.J., Buczek %A F.C., Church %A N., Mackman %A R., Pawlinski %D 2016 %T Supplementary Material for: Protease-Activated Receptor 1 Contributes to Angiotensin II-Induced Cardiovascular Remodeling and Inflammation %U https://karger.figshare.com/articles/figure/Supplementary_Material_for_Protease-Activated_Receptor_1_Contributes_to_Angiotensin_II-Induced_Cardiovascular_Remodeling_and_Inflammation/4249892 %R 10.6084/m9.figshare.4249892.v1 %2 https://ndownloader.figshare.com/files/6929318 %K Protease-activated receptor 1 %K Pre-hypertension %K Angiotensin %K Heart failure %K Fibrosis %X

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.

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