The Hippo pathway in the heart: pivotal roles in development, disease, and regeneration

• Published in: Nature reviews cardiology Vol. 15; no. 11; pp. 672 - 684
• Main Authors: Wang, Jun, Liu, Shijie, Heallen, Todd, Martin, James F
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.11.2018
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Animals; Cardiomyocytes; Care and treatment; Cell Differentiation; Cell Proliferation; Development and progression; Developmental biology; Disease; Fetal Heart - growth & development; Fetal Heart - metabolism; Genetic aspects; Health aspects; Heart; Heart diseases; Heart Diseases - metabolism; Heart Diseases - pathology; Heart Diseases - physiopathology; Heart failure; Homeostasis; Humans; Medical research; Medicine, Experimental; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Organogenesis; Phosphoproteins - metabolism; Physiological aspects; Protein kinases; Protein-Serine-Threonine Kinases - metabolism; Regeneration; Regeneration (Biology); Signal Transduction; Stress response; Transcription Factors; United States
• ISSN: 1759-5002; 1759-5010
• DOI: 10.1038/s41569-018-0063-3

The Hippo-YAP (Yes-associated protein) pathway is an evolutionarily and functionally conserved regulator of organ size and growth with crucial roles in cell proliferation, apoptosis, and differentiation. This pathway has great potential for therapeutic manipulation in different disease states and to promote organ regeneration. In this Review, we summarize findings from the past decade revealing the function and regulation of the Hippo-YAP pathway in cardiac development, growth, homeostasis, disease, and regeneration. In particular, we highlight the roles of the Hippo-YAP pathway in endogenous heart muscle renewal, including the pivotal role of the Hippo-YAP pathway in regulating cardiomyocyte proliferation and differentiation, stress response, and mechanical signalling. The human heart lacks the capacity to self-repair; therefore, the loss of cardiomyocytes after injury such as myocardial infarction can result in heart failure and death. Despite substantial advances in the treatment of heart failure, an enormous unmet clinical need exists for alternative treatment options. Targeting the Hippo-YAP pathway has tremendous potential for developing therapeutic strategies for cardiac repair and regeneration for currently intractable cardiovascular diseases such as heart failure. The lessons learned from cardiac repair and regeneration studies will also bring new insights into the regeneration of other tissues with limited regenerative capacity.