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

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,...

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Veröffentlicht in:Environmental toxicology 2021-07, Vol.36 (7), p.1466-1475
Hauptverfasser: Barik, Parthasarathi, Shibu, Marthandam Asokan, Hsieh, Dennis Jine‐Yuan, Day, Cecilia Hsuan, Chen, Ray‐Jade, Kuo, Wei‐Wen, Chang, Yung‐Ming, Padma, V. Vijaya, Ho, Tsung‐Jung, Huang, Chih‐Yang
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container_issue 7
container_start_page 1466
container_title Environmental toxicology
container_volume 36
creator Barik, Parthasarathi
Shibu, Marthandam Asokan
Hsieh, Dennis Jine‐Yuan
Day, Cecilia Hsuan
Chen, Ray‐Jade
Kuo, Wei‐Wen
Chang, Yung‐Ming
Padma, V. Vijaya
Ho, Tsung‐Jung
Huang, Chih‐Yang
description 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.
doi_str_mv 10.1002/tox.23145
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Vijaya</creatorcontrib><creatorcontrib>Ho, Tsung‐Jung</creatorcontrib><creatorcontrib>Huang, Chih‐Yang</creatorcontrib><title>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</title><title>Environmental toxicology</title><addtitle>Environ Toxicol</addtitle><description>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. 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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.</abstract><cop>Hoboken, USA</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>33881220</pmid><doi>10.1002/tox.23145</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-0627-5470</orcidid><orcidid>https://orcid.org/0000-0002-2097-2240</orcidid></addata></record>
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source Wiley Online Library Journals Frontfile Complete
subjects adipose‐derived stem cells
Ageing
Aging
Angiotensin II
Apoptosis
Cardiac function
Cell therapy
Cell viability
Chinese medicine
Combinatorial analysis
Danggui
Growth factors
Growth rate
Heart rate
Herbal medicine
High-performance liquid chromatography
HPLC
Hypertension
Hypertrophy
In vivo methods and tests
Insulin
insulin‐like growth factor 1 receptor
Intravenous administration
late‐stage hypertension
Liquid chromatography
Muscle contraction
Oral administration
Phalloidin
Receptors
Rhodamine
Stem cell transplantation
Stem cells
Traditional Chinese medicine
title 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
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