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A novel Ca2+ current blocker promotes angiogenesis and cardiac healing after experimental myocardial infarction in mice
Guozhen Cui1,2; Qiqi Xin3; Hisa Hui Ling Tseng2; Maggie PuiMan Hoi2; Yan Wang3,4; Binrui Yang2; InLeng Choi2; Yuqiang Wang5; Rong Yuan3,6; Keji Chen3; Weihong Cong3; Simon MingYuen Lee2
2018-08
Source PublicationPHARMACOLOGICAL RESEARCH
ISSN1043-6618
Volume134Pages:109-117
Abstract

We previously reported a novel danshensu derivative (R)-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (ADTM) that exhibited promising cardiovascular protective activities, such as antioxidant and antiplatelet activities, as well as arterial relaxation. Particularly, ADTM treatment for 24 h exhibited anti-oxidative activity and effectively protected against acute myocardial infarction (MI) in a rat model. Here, we further investigated the pharmacological actions of 14 days of treatment with ADTM in alleviating and restoring the MI size by stimulating revascularization. The pro-angiogenesis activity of ADTM has been validated in multiple experimental models including MI mouse, zebrafish, human umbilical vein endothelial cells (HUVECs) and A7r5 vascular smooth muscle cells (VSMCs). In addition, the effect of ADTM on L-type Ca2+ current (ICaL) was determined. We demonstrated that ADTM (12–24 mg/kg) treatment for 14 days significantly decreased myocardial infarct size, increased the blood vessel density compared to vehicle in the myocardial peri-infarct area, and ADTM (24 mg/kg) enhanced the serum VEGF level in MI mice (P < 0.05). We also demonstrated that treatment with ADTM at 50–200 μM rescued chemical-induced blood vessel loss in zebrafish. Although ADTM did not directly promote the features of angiogenesis in HUVECs, ADTM significantly increased VEGF production in a dose-dependent manner in A7r5 cells (P < 0.05). A patch clamp experiment demonstrated that ADTM (200 μM) inhibited ICaL at all depolarizing voltages, with > 50% inhibition at + 10 mV. Taken together, our results indicated that ADTM served as a Ca2+ current blocker, promoted angiogenesis and reduced experimental myocardial infarct size in mice, probably through stimulation of VEGF production in VSMCs.

KeywordCardioprotection Angiogenesis Adtm Zebrafish Vegf
DOI10.1016/j.phrs.2018.06.005
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000442708500011
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
University of Macau
Affiliation1.Zhuhai key laboratory of basic and applied research in Chinese medicine, Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
2.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China
3.Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
4.National Integrated Traditional and Western Medicine Center for Cardiovascular Disease, China-Japan Friendship Hospital, Beijing, China
5.Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, China
6.Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Guozhen Cui,Qiqi Xin,Hisa Hui Ling Tseng,et al. A novel Ca2+ current blocker promotes angiogenesis and cardiac healing after experimental myocardial infarction in mice[J]. PHARMACOLOGICAL RESEARCH,2018,134:109-117.
APA Guozhen Cui.,Qiqi Xin.,Hisa Hui Ling Tseng.,Maggie PuiMan Hoi.,Yan Wang.,...&Simon MingYuen Lee.(2018).A novel Ca2+ current blocker promotes angiogenesis and cardiac healing after experimental myocardial infarction in mice.PHARMACOLOGICAL RESEARCH,134,109-117.
MLA Guozhen Cui,et al."A novel Ca2+ current blocker promotes angiogenesis and cardiac healing after experimental myocardial infarction in mice".PHARMACOLOGICAL RESEARCH 134(2018):109-117.
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