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.

journal_name

Cell Transplant

journal_title

Cell transplantation

authors

Huang CY,Chen SY,Fu RH,Huang YC,Chen SY,Shyu WC,Lin SZ,Liu SP

doi

10.3727/096368915X686995

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

561-71

issue

3

eissn

0963-6897

issn

1555-3892

pii

content-CT-2540_Huang_et_al

journal_volume

24

pub_type

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