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

Abstract

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.

Repression of miR-764-5p by enhancing IGF1R and cochaperone CHIP expression in mesenchymal stem cells (MSCs) regulates cardioprotective effects in Aging-Spontaneously Hypertensive rats model

“…Next, the characterization of stem cell surface markers such as CD90 positive marker and CD45 negative marker indicated the con rmation of stemness by ow cytometry analysis in rADSCs (Supplementary Fig. 1d) and also additional stem cell surface markers characterized in our previous report 28 , 23 . Taken together, short-term hypoxia induces migration rate, cell viability with higher S-phase and target proteins expression compared to normoxia and long-term hypoxia conditions in rADSCs.…”

“…The following assay was performed and mentioned in our previous report 23 . In brief, the colorimetric assay was done to analyze the viability of the cells on the mechanism based on the conversion of MTT reagent (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide) into the nal product formazan to produce the blue color formation.…”

Leu27IGF‐II‐induced hypertrophy in H9c2 cardiomyoblasts is ameliorated by saffron by regulation of calcineurin/NFAT and CaMKIIδ signaling

“…Development of alternative and/or complementary strategies to ameliorate maladaptive cardiac hypertrophy has garnered much popularity over the decades. 1,[36][37][38][39][40][41][42][43] In this regard, Saffron as a medicinal plant F I G U R E 3 Effects of CSE on Leu 27 IGF-II-induced hypertrophy. H9c2 cells were treated with CSE following induction with Leu 27 IGF-II and the expression levels of calcineurin, NFATc3, p-GATA4, CaMKII, p-HDAC4, p-HDAC5, and BNP, involved in cardiac hypertrophy were analyzed through Western blotting (A) n = 4.…”

“…Development of alternative and/or complementary strategies to ameliorate maladaptive cardiac hypertrophy has garnered much popularity over the decades 1,36–43 . In this regard, Saffron as a medicinal plant with many therapeutic effects on the vascular function gains attraction for its possible clinical application.…”

Stem cell therapy for cardiac regeneration: key points

“…In culture, ASCs produce a number of cytokines (vascular endothelial growth factor, hepatocyte growth factor, insulin-like growth factor-1) that have cardioprotective effects [8]. As a result, transplanted adipose tissue stem cells can improve the heart's contractile function and its vascularization [71].…”