Notch3 deficiency impairs coronary microvascular maturation and reduces cardiac recovery after myocardial ischemia

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:236

Article

Tao, Yong-Kang^1,2  Zeng, Heng¹  Zhang, Guo-Qiang²  Chen, Sean T.⁴  Xie, Xue-Jiao^1,3  He, Xiaochen¹  Wang, Shuo¹  Wen, Hongyan³  Chen, Jian-Xiong^1,3 

[1] Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, 2500 North State St, Jackson, MS 39216 USA

[2] China Japan Friendship Hosp, Emergency Dept, Beijing 100029, Peoples R China

[3] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China

[4] Duke Univ, Sch Med, Durham, NC 27706 USA

关键词: Notch3 deficiency;    Pericytes;    Vascular maturation;    Myocardial infarction;    Vascular progenitor cells;   

DOI  :  10.1016/j.ijcard.2017.01.096

来源: Elsevier

【 摘 要 】

Rationale: Vascular maturation plays an important role in wound repair post-myocardial infarction (MI). The Notch3 is critical for pericyte recruitment and vascular maturation during embryonic development. Objective: This study is to test whether Notch3 deficiency impairs vascular maturation and blunts cardiac functional recovery post-MI. Approach and results: Wild type (WT) and Notch3 knockout (Notch3KO) mice were subjected to MI by the ligation of left anterior descending coronary artery (LAD). Cardiac function and coronary blood flow reserve (CFR) were measured by echocardiography. The expression of angiogenic growth factor, pericyte/capillary coverage and arteriolar formation were analyzed. Loss of Notch3 in mice resulted in a significant reduction of pericytes and small arterioles. Notch3 KO mice had impaired pericyte/capillary coverage and CFR compared to WT mice. Notch3 KO mice were more prone to ischemic injury with larger infarcted size and higher rates of mortality. The expression of CXCR-4 and VEGF/Ang-1 was significantly decreased in Notch3KO mice. Notch3 KO mice also had few NG2(+)/Sca1(+) and NG2(+)/c-kit(+) progenitor cells in the ischemic area and exhibited worse cardiac function recovery at 2 weeks after MI. These were accompanied by a significant reduction of pericyte/capillary coverage and arteriolar maturation. Furthermore, Notch3 KO mice subjected to MI had increased intracellular adhesion molecule-2 (ICAM-2) expression and CD11b(+) macrophage infiltration into ischemic areas compared to that of WT mice. Conclusion: Notch3 mutation impairs recovery of cardiac function post-MI by the mechanisms involving the preexisting coronary microvascular dysfunction conditions, and impairment of pericyte/progenitor cell recruitment and microvascular maturation. (C) 2016 Published by Elsevier Ireland Ltd.

【 授权许可】

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