Aortic constriction induces hypertension and cardiac hypertrophy via (pro)renin receptor activation and the PLC‑β3 signaling pathway.

Junyan Wu, Cong Zhang, Chuanjun Liu, Aihua Zhang, An Li, Jingjun Zhang, Yanling Zhang

Molecular medicine reports 2019 Jan

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The (pro)renin receptor [(P)RR] serves an important role in cardiovascular complications. However, the precise mechanisms of (P)RR in the heart remain obscure. The authors hypothesized that overexpression of (P)RR would be associated with activation of the relevant signal pathway which could lead to organ injury. The aim of the present study was to test the role of cardiac (P)RR and its potential signaling pathway components including phospholipase C (PLC), protein kinase C (PKC), extracellular signal‑regulated kinase (ERK)1/2 and Raf‑1 proto‑oncogene, serine/threonine kinase (Raf‑1). Hypertension and cardiac hypertrophy were induced by partial abdominal aortic ligation in Sprague‑Dawley rats. The expression levels of cardiac (P)RR, PLC‑β3, PKC, ERK1/2 and Raf‑1 were measured following administration of the handle region peptide (HRP) and PLC‑β3 inhibitor U73122. The expression of (P)RR and PLC‑β3 significantly increased in the left ventricle (P<0.05). Levels of PKC‑α, ERK1/2 and Raf‑1 in the heart rose significantly (P<0.05). HRP and U73122 significantly decreased the levels of cardiac (P)RR and PLC‑β3. Furthermore, levels of PKC‑α, ERK1/2 and Raf‑1 were also decreased (P<0.05). Cardiac parameters, blood pressure and plasma Angiotensin (Ang) I and Ang II levels were altered significantly (P<0.05). The results demonstrated that hypertension induced by aortic restriction activated the (P)RR in the heart. This action led to hypertension and cardiac hypertrophy via the (P)RR‑PLC‑β3‑PKC‑ERK1/2‑Raf‑1 signaling pathway. These results provide a mechanism by which elevated (P)RR levels in hypertension may contribute to the development of cardiac remodeling.

Citation

Junyan Wu, Cong Zhang, Chuanjun Liu, Aihua Zhang, An Li, Jingjun Zhang, Yanling Zhang. Aortic constriction induces hypertension and cardiac hypertrophy via (pro)renin receptor activation and the PLC‑β3 signaling pathway. Molecular medicine reports. 2019 Jan;19(1):573-580