title: Differentiation of embryonic stem cells into cardiomyocytes used to investigate the cardioprotective effect of salvianolic acid B through BNIP3 involved pathway.
abstract: Cardiovascular diseases are related to many risk factors, such as diabetes, high blood pressure, smoking, and obesity. Myocardial infarction (MI), a cardiovascular disease, is the most common cause of cardiomyocyte death. In MI, hypoxia induces cardiomyocyte apoptosis; in particular, diabetes combined with MI has a synergistic effect that exacerbates cardiomyocyte death. The hypoxia-inducible factor-1α (HIF1α) transcriptional factor and a BH-3 only protein, Bcl-2 adenovirus E1B 19-kDa interacting protein 3 (BNIP3), are known to play fundamental roles in both adaptive and cell death processes in response to hypoxia. In addition, most cardioprotective studies used H9c2 cells that were not beating, so H9c2 cells may not be the best model for testing cardioprotective effects. Embryonic stem cells (ESCs) are pluripotent stem cells that are able to differentiate into several types of cells, including cardiomyocytes. In this study, we reveal a simple method to differentiate ESCs into cardiomyocytes by using poly-d-lysine-coated plates combined with ITS and N2-containing medium and characterized the ESC-derived cardiomyocytes by cardiomyocyte marker staining. The ESC-derived cardiomyocytes were used to investigate the protective effect of salvianolic acid B (Sal-B) in high glucose combined with hypoxic conditions to mimic diabetes patients with ischemia. The results of MTT and TUNEL assays indicate that Sal-B suppresses the apoptotic effect of treatment with high glucose combined with hypoxia in ESC-derived cardiomyocytes. In particular, Sal-B inhibited HIF1α, BNIP3, and cleavage caspase 3 expression levels, thereby suppressing apoptosis. This is the first study to mention the correlation between BNIP3 and Sal-B for cardioprotective effects. In conclusion, we suggest that Sal-B may be suitable for use as a future cardioprotective medicine.
authors: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors: Chih-Yang
authors: CY
authors: Huang
authors: Shao-Yu
authors: SY
authors: Chen
authors: Ru-Huei
authors: RH
authors: Fu
authors: Yu-Chuen
authors: YC
authors: Huang
authors: Shih-Yin
authors: SY
authors: Chen
authors: Woei-Cherng
authors: WC
authors: Shyu
authors: Shinn-Zong
authors: SZ
authors: Lin
authors: Shih-Ping
authors: SP
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D011107:Polylysine / Q000737:chemistry; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D053630:Depsides
chemical_list: D001572:Benzofurans; D053148:Caspase 3; D005947:Glucose; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011107:Polylysine; D020011:Protective Agents; C505650:BNIP3 protein, rat; C076944:salvianolic acid B; D053630:Depsides