Transforming Growth Factor β Signaling Pathway as a Potential Drug Target in Treating Aortic Diseases

Review Transforming Growth Factor β Signaling Pathway as a Potential Drug Target in Treating Aortic Diseases Zijie Liu 1,2, Tianyu Song 3, and Liping Xie 1,2,3, * 1 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China 2 School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China 3 ‍Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing 211166, China * Correspondence: lipingxie@njmu.edu.cn Received: 16 October 2023 Accepted: 20 November 2023 Published: 6 March 2024 Abstract: The transforming growth factor β (TGF-‍β) signaling pathway is crucial for preserving the structural homeostasis of the aorta and promoting aortic development. This pathway encompasses both SMAD-dependent canonical pathway and SMAD-independent non-canonical signaling pathway. Heritable thoracic aortic aneurysms and dissection are highly correlated with genetic alterations in TGF-‍β canonical signaling-related genes. However, depending on the stage of the disease, the TGF-‍β signaling pathway can have either inhibitory or aggravation effects, making its roles in aortic disease complex and occasionally contradictory. This review aims to elucidate the biological mechanisms underlying the TGF-‍β signaling pathway in the most common aortic diseases, namely acute aortic syndromes and aortic aneurysms, and to evaluate the potential clinical application of TGF-β-targeting therapies in aortic diseases.