Semaphorin3E-PlexinD1 signaling in coronary artery and lymphatic vessel development with clinical implications in myocardial recovery

• Published in: iScience 2021-04, Vol.24 (4), p.102305, Article 102305
• Main Authors: Maruyama, Kazuaki, Naemura, Kazuaki, Arima, Yuichiro, Uchijima, Yasunobu, Nagao, Hiroaki, Yoshihara, Kenji, Singh, Manvendra K., Uemura, Akiyoshi, Matsuzaki, Fumio, Yoshida, Yutaka, Kurihara, Yukiko, Miyagawa-Tomita, Sachiko, Kurihara, Hiroki
• Format: Article
• Language: English
• Subjects: Biological Sciences; Cell Biology; Developmental Biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2021.102305

Blood and lymphatic vessels surrounding the heart develop through orchestrated processes from cells of different origins. In particular, cells around the outflow tract which constitute a primordial transient vasculature, referred to as aortic subepicardial vessels, are crucial for the establishment of coronary artery stems and cardiac lymphatic vessels. Here, we revealed that the epicardium and pericardium-derived Semaphorin 3E (Sema3E) and its receptor, PlexinD1, play a role in the development of the coronary stem, as well as cardiac lymphatic vessels. In vitro analyses demonstrated that Sema3E may demarcate areas to repel PlexinD1-expressing lymphatic endothelial cells, resulting in proper coronary and lymphatic vessel formation. Furthermore, inactivation of Sema3E-PlexinD1 signaling improved the recovery of cardiac function by increasing reactive lymphangiogenesis in an adult mouse model of myocardial infarction. These findings may lead to therapeutic strategies that target Sema3E-PlexinD1 signaling in coronary artery diseases. [Display omitted] •Sema3E-PlexinD1 signaling regulates coronary and cardiac lymphatic vessel development•Sema3E demarcate areas to repel PlexinD1-expressing lymphatic endothelial cells•Inhibition of Sema3E-PlexinD1 signaling improves the recovery after myocardial injury Biological Sciences; Cell Biology; Developmental Biology