Deficiency of GDF-11 Accelerates TAC-Induced Heart Failure by Impairing Cardiac Angiogenesis

• Published in: JACC. Basic to translational science 2023-06, Vol.8 (6), p.617-635
• Main Authors: Zhu, Jinyun, Zhang, Ning, Zhao, Yun, Liu, Qi, Wang, Yingchao, Chen, Mingyao, Ma, Qunchao, Dong, Aiqiang, Wang, Yaping, Yu, Hong
• Format: Article
• Language: English
• Subjects: angiogenesis; cardiac hypertrophy; fibrosis; GDF-11; heart failure; Original Research - Preclinical
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2022.11.004

[Display omitted] •Lack of GDF-11 does not influence the heart development and physiological growth.•However, GDF-11 deficient in cardiomyocytes leads to cardiac remodeling and eventually heart failure under pressure overload.•GDF-11 acts as an autocrine/paracrine factor to regulate the local cardiac function through promoting angiogenesis via the Akt/mTOR pathway.•Maintaining GDF-11 homeostasis in the heart improves and rescues contractile dysfunction following pressure overload. The role of growth differentiation factor (GDF)-11 in cardiac diseases has not been fully determined. Our study revealed that GDF-11 is not essential for myocardial development and physiological growth, whereas its absence exacerbates heart failure under pressure overload condition via impairing the responsive angiogenesis. GDF-11 induced VEGF expression in CMs by activating the Akt/mTOR pathway. The effect of endogenous GDF-11 on the heart belongs to local self-regulation of myocardial tissue, rather than a way of systemic regulation.