| First Author | Sato T | Year | 2019 |
| Journal | Int J Mol Sci | Volume | 20 |
| Issue | 2 | PubMed ID | 30634441 |
| Mgi Jnum | J:286354 | Mgi Id | MGI:6403608 |
| Doi | 10.3390/ijms20020239 | Citation | Sato T, et al. (2019) Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling. Int J Mol Sci 20(2):239 |
| abstractText | Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1(-)7-dependent manner. Whether apelin antagonizes the over-activation of the renin(-)angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-beta) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-beta expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling. |
