Abstract 13155: Apelin and Apela for Therapy of Myocardial Fibrosis and Heart Failure

• Published in: Circulation (New York, N.Y.) Vol. 146; no. Suppl_1
• Main Authors: Kemppi, Anna, Rahtu-Korpela, Lea M, Szabo, Zoltan, Raatikainen, Sami, Anisimov, Andrey, Alitalo, Kari K, Magga, Johanna, Kerkela, Risto
• Format: Journal Article
• Language: English
• Published: 08.11.2022
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.146.suppl_1.13155

Abstract only The apelin/apela – apelin receptor system regulates a variety of physiological cardiovascular functions including vascular tone, cardiac contractility, angiogenesis, and energy metabolism. However, the cell type specific effects of apelin/apela in the cardiovascular system are not well understood. The aim of this study was to investigate the potential role of apelin and apela in regulating development of myocardial fibrosis and to identify the signaling mechanisms underlying the anti-fibrotic effects. To investigate the role of apelin and apela in vivo , 2-month-old C57BL/6N male mice were injected with AAV9.LacZ, AAV9.Apelin or AAV9.Apela and subjected to thoracic aortic constriction (TAC) for 6 weeks. Echocardiography analysis at the end of the study showed that overexpression of either apelin or apela attenuated TAC-induced left ventricular (LV) dysfunction and increase in LV mass. Analysis of cardiac tissue showed downregulation of collagen I and fibrosis related periostin mRNA expression levels and reduced accumulation of interstitial fibrosis in the left ventricles of mice overexpressing apelin or apela. Studies in human cardiac fibroblasts in vitro showed that apelin and apela attenuate TGFβ1-induced collagen expression and secretion. Analyses of LV tissue and human fibroblast samples indicated that apelin and apela regulate the stress-induced activation of MAPK pathways. Chemical inhibitors and genetic modification of specific signaling elements identified p38 MAPK as a central signaling pathway mediating the inhibitory effect of apelin and apela on TGFβ1 signaling and TGFβ1-induced collagen production. In summary, we show that apelin and apela attenuate hemodynamic pressure overload -induced LV dysfunction and myocardial fibrosis and identify a novel signaling mechanism regulating the response. Our data suggests that activation of apelinergic signaling could offer a novel therapeutic approach to prevent the development of cardiac fibrosis and heart failure.