Tanshinone I prevents atorvastatin-induced cerebral hemorrhage in zebrafish and stabilizes endothelial cell–cell adhesion by inhibiting VE-cadherin internalization and actin-myosin contractility. (February 2018)

• Record Type: Journal Article
• Authors: Huang, Bin; Zhou, Zhong-Yan; Li, Shang; Huang, Xiao-Hui; Tang, Jing-Yi; Hoi, Maggie Pui Man; Lee, Simon Ming Yuen
• Is Part Of: Pharmacological research. Volume 128(2018)
• Page Start: 389
• Page End: 398
• Publication Date: 2018-02
• Subjects: Tanshinone I -- Vascular integrity -- Endothelial cell adhesion -- Hemorrhagic stroke -- Zebrafish -- HUVECs; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2017.09.025
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Defects in vascular integrity in cerebrovasculature lead to serious pathologies including hemorrhagic stroke. The stability of cell adhesion junctions and actin-myosin contractile machinery are two major determinants for the integrity of endothelial monolayer. Here we have evaluated the protective effects of tanshinone I (Tan I), a lipophilic compound presents in Salvia miltiorrhiza, against atorvastatin-induced cerebral hemorrhage in zebrafish in vivo, and further dissected the molecular mechanisms in HUVECs. We demonstrated that Tan I protected endothelial integrity by stabilizing cell–cell adhesion junctions via the inhibition of Src-mediated VE-cadherin internalization and subsequent junction-linked actin cytoskeleton depolymerization. In addition, Tan I inhibited ROCK-associated endothelial contractile machinery by dephosphorylating cofilin and MYPT1. These findings identified Tan I as an endothelial stabilizing agent and suggested Tan I as a potential treatment for vascular leakage in hemorrhagic stroke.