PUBLICATION
A novel Ca2+ current blocker promotes angiogenesis and cardiac healing after experimental myocardial infarction in mice.
- Authors
- Cui, G., Xin, Q., Tseng, H.H.L., Hoi, M.P., Wang, Y., Yang, B., Choi, I., Wang, Y., Yuan, R., Chen, K., Cong, W., Lee, S.M.
- ID
- ZDB-PUB-180612-5
- Date
- 2018
- Source
- Pharmacological research 134: 109-117 (Journal)
- Registered Authors
- Keywords
- ADTM, Cardioprotection, VEGF, angiogenesis, zebrafish
- MeSH Terms
-
- Angiogenesis Inducing Agents/pharmacology*
- Animals
- Animals, Genetically Modified
- Calcium Channel Blockers/pharmacology*
- Calcium Channels, L-Type/drug effects*
- Calcium Channels, L-Type/metabolism
- Calcium Signaling/drug effects
- Cell Line
- Disease Models, Animal
- Human Umbilical Vein Endothelial Cells/drug effects
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- Male
- Mice, Inbred C57BL
- Myocardial Infarction/drug therapy*
- Myocardial Infarction/metabolism
- Myocardial Infarction/pathology
- Myocardial Infarction/physiopathology
- Myocytes, Cardiac/drug effects*
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- Neovascularization, Physiologic/drug effects*
- Phenylpropionates/pharmacology*
- Pyrazines/pharmacology*
- Rats
- Vascular Endothelial Growth Factor A/blood
- Wound Healing/drug effects*
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 29890255 Full text @ Pharmacol. Res.
Citation
Cui, G., Xin, Q., Tseng, H.H.L., Hoi, M.P., Wang, Y., Yang, B., Choi, I., Wang, Y., Yuan, R., Chen, K., Cong, W., Lee, S.M. (2018) A novel Ca2+ current blocker promotes angiogenesis and cardiac healing after experimental myocardial infarction in mice.. Pharmacological research. 134:109-117.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping