Physical training prior to myocardial infarction potentializes stem cell therapy, SDF-1/CXCR4 axis activation and inhibits the vasoconstrictor response in hypertensive rats. (February 2020)

• Record Type: Journal Article
• Authors: Schaun, Maximiliano I.; Kristochek, Melissa; Dias, Lucinara Dadda; Peres, Thiago Rodrigues; Lehnen, Alexandre M.; Irigoyen, Maria Cláudia; Markoski, Melissa M.
• Is Part Of: Cytokine. Volume 126(2020)
• Publication Date: 2020-02
• Subjects: Stem cells -- Physical training -- Cell homing -- Myocardial infarction; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2019.154912
• Languages: English
• ISSNs: 1043-4666

Abstract

Graphical abstract: Highlights: Our study is the first to demonstrate activation of SDF-1/CXCR4 axis as a protective/ effect provided by physical training to heart tissue prior to AMI in SHR. We found an associated systemic reduction in short time vasoconstrictor and inflammatory responses after AMI in trained animals. Physical training resulted in increased expression of inflammatory factors in the heart tissue after AMI, which potentiates stem cell regenerative capacity. Abstract: Stem cell therapy is a promising strategy for recovering of injured cardiac tissue after acute myocardial infarction. The effects promoted by preventive physical training, beneficial for regeneration, are not yet understood on stem cell homing. In the present study, we evaluated the effect of preventive physical training on cell homing activation and associated mechanisms after acute myocardial infarction and therapy with adipose-derived stem cells in spontaneously hypertensive rats (SHR). Forty female SHR were allocated in sedentary (S), sedentary SHAM (S-SHAM), sedentary AMI (S-AMI), sedentary with cell therapy (S-ICT), aerobically trained (T), trained SHAM (T-SHAM), trained AMI (T-AMI) and trained with cell therapy (S-ICT) groups. Cell therapy was performed through the infusion of 2 × 10 5 ADSC/0.05 mL at the moment of AMI. Molecular markers of cell homing (SDF-1/CXCR4), inflammatory response (myeloperoxidase and cardiac expression of iNOS, gp91phox and NFkB), vasoconstrictor agents (Ang II and ET-1) and an angiogenesis inducer (VEGF) were measured. Functional capacity and echocardiographic parameters were also evaluated. Preventive physical training associated with cell therapy was able to reduce left ventricle ejection fraction losses in infarcted animals. Results demonstrated activation of the SDF-1/CXCR4 axis by physical training, besides a reduction in vasoconstrictor and systemic inflammatory responses. Physical training prior to AMI was able to induce a cardioprotective effect and optimize the reparative mechanism of cell therapy in an animal model of hypertension.