TY - JOUR
T1 - Cardioprotective effects of transplanted adipose-derived stem cells under Ang II stress with Danggui administration augments cardiac function through upregulation of insulin-like growth factor 1 receptor in late-stage hypertension rats
AU - Barik, Parthasarathi
AU - Shibu, Marthandam Asokan
AU - Hsieh, Dennis Jine Yuan
AU - Day, Cecilia Hsuan
AU - Chen, Ray Jade
AU - Kuo, Wei Wen
AU - Chang, Yung Ming
AU - Padma, V. Vijaya
AU - Ho, Tsung Jung
AU - Huang, Chih Yang
N1 - Funding Information:
This study was supported in part by the China Medical University, and Asia University grants (CMU106‐ASIA‐04), Ministry of Science and Technology (MOST 106‐2320‐B‐039‐016‐MY3, MOST 106‐2811‐B‐039‐035).
Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2021/7
Y1 - 2021/7
N2 - In aging hypertensive conditions, deterioration of insulin-like growth factor 1 receptor (IGF1R) cause a pathological impact on hypertensive hearts with an increased Ang II level. Recovering these adverse conditions through transplanted adipose-derived stem cells is a challenging approach. Moreover, Danggui, a Traditional Chinese medicine (TCM), is used for the treatment of cardioprotective effects. In this study, to evaluate whether the combined effect of MSCs and TCM can recover the cardiac function in late-stage hypertension rats. We observed that lower dose of Danggui crude extract treatment showed an increased level of cell viability with maintained stemness properties and growth rate in rat adipose-derived stem cells (rADSCs). Further, we cocultured the H9c2 cells with rADSCs and the results revealed that Danggui-treated MSCs enhanced the IGF1R expression and attenuated the hypertrophy in H9c2 cells against Ang II challenge by immunoblot and rhodamine-phalloidin staining. In addition, Danggui crude extract was also quantified and characterized by HPLC and LC–MS analysis. Furthermore, the in vivo study was performed by considering 11 months old rats (n = 7). Importantly, the oral administration of Danggui crude extract with stem cells intravenous injection in SHR-D-ADSCs group showed a combination effect to augment the cardiac function through enhancement of ejection fraction, fractional shortening, contractility function in the late-stage hypertension conditions. We have also observed a decreased apoptosis rate in the heart tissue of SHR-D-ADSCs group. Taken together, these results indicate that the combinatorial effects of Danggui crude extract and stem cell therapy enhanced cardiac function in late-stage SHR rats.
AB - In aging hypertensive conditions, deterioration of insulin-like growth factor 1 receptor (IGF1R) cause a pathological impact on hypertensive hearts with an increased Ang II level. Recovering these adverse conditions through transplanted adipose-derived stem cells is a challenging approach. Moreover, Danggui, a Traditional Chinese medicine (TCM), is used for the treatment of cardioprotective effects. In this study, to evaluate whether the combined effect of MSCs and TCM can recover the cardiac function in late-stage hypertension rats. We observed that lower dose of Danggui crude extract treatment showed an increased level of cell viability with maintained stemness properties and growth rate in rat adipose-derived stem cells (rADSCs). Further, we cocultured the H9c2 cells with rADSCs and the results revealed that Danggui-treated MSCs enhanced the IGF1R expression and attenuated the hypertrophy in H9c2 cells against Ang II challenge by immunoblot and rhodamine-phalloidin staining. In addition, Danggui crude extract was also quantified and characterized by HPLC and LC–MS analysis. Furthermore, the in vivo study was performed by considering 11 months old rats (n = 7). Importantly, the oral administration of Danggui crude extract with stem cells intravenous injection in SHR-D-ADSCs group showed a combination effect to augment the cardiac function through enhancement of ejection fraction, fractional shortening, contractility function in the late-stage hypertension conditions. We have also observed a decreased apoptosis rate in the heart tissue of SHR-D-ADSCs group. Taken together, these results indicate that the combinatorial effects of Danggui crude extract and stem cell therapy enhanced cardiac function in late-stage SHR rats.
KW - adipose-derived stem cells
KW - cardiac function
KW - Danggui
KW - insulin-like growth factor 1 receptor
KW - late-stage hypertension
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U2 - 10.1002/tox.23145
DO - 10.1002/tox.23145
M3 - Article
C2 - 33881220
AN - SCOPUS:85104530144
SN - 1520-4081
VL - 36
SP - 1466
EP - 1475
JO - Environmental Toxicology
JF - Environmental Toxicology
IS - 7
ER -