Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction

Abstract

Mesenchymal stem cells (MSCs) have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction (AMI). However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefore, the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI. In this paper, MSCs isolated from rat inguinal fat tissues were termed as adiposederived mesenchymal stem cells (ASCs), and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs. Fourteen days later, GATA-4 (a transcription factor) and cardiac troponin-I were detected by cellular immunofluorescence. Atorvastatin (Ator group) or vehicle (control group) was administrated for the first 24 h after AMI production in rats. Fourteen days later, inflammatory parameters and cardiac function were evaluated. The other surviving rats were injected with a total of 1 3 10 6 co-ASCs/100 ml phosphate-buffered saline (PBS), 1310 6 ASCs/100 ml PBS, or 100 ml PBS. Twenty-eight days after cell injection, survival and differentiated rates of transplanted cells and cardiac function were evaluated. The percentage of GATA-4 expression in co-ASCs was 28.5% + + + + + 5.6% and of cardiac troponin-I was 22.8% + + + + + 3.2%. Compared with the control group, the number of infiltrating inflammatory cells, myeloperoxidase activity, inflammatory cytokines (VCAM-1, TNF-a, Hs-CRP) mRNA expression, and Bax protein expression were significantly reduced in the three Ator groups, accompanied by a significant improvement of Bcl-2 protein expression and cardiac function (P < 0.05). Compared with the Ator2 1 ASCs group and Con 1 co-ASCs group, the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I-positive transplanted cells, concomitant with cardiac function, were improved most prominently in the Ator3 1 co-ASCs group (P < 0.05). Pre-amelioration of the cardiac milieu, in conjunction with prespecification of ASCs, was beneficial for enhancing ASCs' therapeutic efficacy on cardiac function after AMI.

Additive effects of atorvastatin combined with sitagliptin on rats with myocardial infarction: a pilot study

“…For example, Cai et al . reported that in rats with acute myocardial infarction, atorvastatin therapy is beneficial for reducing inflammatory cytokine expression as well as decreasing leukocyte infiltration [10]. In addition, through improving endothelial function, statin therapy reduces leukocytes trans-endothelium migration, and the mechanism is associated with statins’ effect on inhibiting ROCK [15].…”

“…Briefly, induction of MI was performed as previously described by permanent ligation of the left anterior descending coronary artery with the help of ventilation (tidal volume, 6.0 ml; respiratory rate, 70 cycles/min) [10]. Thereafter, the surviving 37 rats were randomly divided into 4 groups as follows: atorvastatin group (10 mg/kg daily, oral gavage, n = 9), sitagliptin group (10 mg/kg daily, oral gavage, n = 9), combined group (10 mg/kg daily atorvastatin plus 10 mg/kg daily sitagliptin, n = 9), and control group (3 ml of normal saline daily, oral gavage, n = 10).…”

Atorvastatin Improves Microenvironment to Enhance the Beneficial Effects of BMSCs Therapy in a Rabbit Model of Acute Myocardial Infarction

“…Existing evidence suggests that ischemia and hypoxia, inflammation, apoptosis, oxidative stress, and neuroendocrine activation together create a grim and adverse microenvironment in the infracted myocardium to threaten the survival of implanted stem cells [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]. Clearly, maximizing the survival rate of transplanted cells is a critical step towards maximizing the potential of stem cell therapy for AMI.…”

“…Recent studies have demonstrated that combined therapy with mesenchymal stem cells (MSCs) and atorvastatin, a blood cholesterol-lowering agent, produces synergistic beneficial effects in the treatment of AMI, despite that neither atorvastatin nor MSCs can individually improve ventricular function significantly [15,16,17,18,19,20,21]. These findings retrieved the declining interest in applying and investigating stem cell therapy of AMI, and stirred up new surges for searching better strategies to boost MSCs therapy: combined MSCs therapy and pharmacotherapy is one of these proof-in-principle approaches.…”

Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure: Part I

“…Il principale ostacolo al loro utilizzo è il tempo che impiegano per differenziarsi in cardiomiociti, circa 14 giorni, e la necessità prima della somministrazione di un trattamento che ne aumenti la resistenza all'ipossia e ai radicali liberi facilitando il loro attecchimento nella zona infartuata [50]. A questo scopo sono state messe in pratica diverse strategie, come la somministrazione di fattori di crescita (BMP, IGF-1, FGF) [51], di farmaci [52,53] (atorvastatina, estrogeni) o l'utilizzo di biomateriali come veicoli.…”