Hydroxysafflor yellow A promotes neovascularization and cardiac function recovery through HO-1/VEGF-A/SDF-1α cascade.

Abstract

AIM:

The present study was to investigate the proangiogenic and cardioprotective effects of hydroxysafflor yellow A (HSYA) against myocardial infarction (MI) injury and the underlying mechanisms.

METHODS:

MI model was induced by ligation of the left coronary artery in normal and heme oxygenase-1 (HO-1) knockout mice and the ones receiving vascular endothelial growth factor-A (VEGF-A) or stromal cell-derived factor-1α (SDF-1α) antagonists. They were treated with three doses or single dose of HSYA for 28days. The cardiac function, endothelial progenitor cells (EPCs) mobilization, angiogenesis, the expression of HO-1, VEGF-A, SDF-1α and apoptosis or fibrosis related proteins in the peri-infarct area were evaluated at respective times. We further examined the effect of HSYA on EPCs CXC chemokiner receptor 4 (CXCR4) expression and the role of SDF-1α on EPCs function in vitro.

RESULTS:

HSYA could dose dependently reduce left ventricular function impairment, myocardial apoptosis and fibrosis, and promote EPCs mobilization and myocardial neovascularization. Further, HO-1 knockout abolished HSYA-induced up-regulation of HO-1, VEGF-A and SDF-1α. VEGF antagonist significantly reduced HSYA-increased VEGF-A and SDF-1α levels and SDF-1 antagonist abolished HSYA-simulated up-regulation of SDF-1α. Meanwhile, HO-1 knockout, administration of VEGF and SDF-1 antibodies abrogated HSYA-promoted expression of the marker proteins of newborn microvessels and cardiac functional recovery. In vitro, HSYA dose dependently promoted (CXCR4) expression on EPCs. SDF-1α significantly accelerated EPCs function which was reversed by CXCR4 antagonist.

CONCLUSION:

HSYA could promote EPCs function through the HO-1/VEGF-A/SDF-1α signaling cascade, which contributed largely to myocardial neovascularization and further improved cardiac function in MI mice.

• Authors: Guo Wei, Ying Yin, Jialin Duan, Chao Guo, Yanrong Zhu, Yanhua Wang, Miaomiao Xi, Aidong Wen
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 88 Pg. 409-420 (Apr 2017) ISSN: 1950-6007 [Electronic] France
• PMID: 28122306 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Chemokine CXCL12
• Quinones
• Receptors, CXCR4
• Vascular Endothelial Growth Factor A
• hydroxysafflor yellow A
• Chalcone
• Heme Oxygenase-1

Topics

• Animals
• Cell Proliferation (drug effects)
• Chalcone (analogs & derivatives, chemistry, pharmacology, therapeutic use)
• Chemokine CXCL12 (metabolism)
• Endothelial Progenitor Cells (drug effects, metabolism)
• Heart (drug effects, physiopathology)
• Heart Function Tests (drug effects)
• Heme Oxygenase-1 (metabolism)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Myocardial Infarction (drug therapy, pathology, physiopathology)
• Neovascularization, Physiologic (drug effects)
• Quinones (chemistry, pharmacology, therapeutic use)
• Receptors, CXCR4 (metabolism)
• Recovery of Function (drug effects)
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)
• Vascular Endothelial Growth Factor A (metabolism)