Myocardial apoptosis and mesenchymal stem cells with acute exercise

Abstract

Aerobic exercise confers many health benefits. However, numerous reports have shown that acute aerobic exercise can injure the heart. We tested the general hypothesis that acute moderate‐intensity exercise in rodents induces cardiomyocyte damage and stimulates mesenchymal stem cells (MSCs) to increase paracrine‐mediated protective effects on cardiomyocytes. A single session of treadmill running (13 m/min, 0% grade, for 45 min) in untrained C57BL/6 male mice (n = 18) increased cleaved poly ADP‐ribose polymerase (PARP), a marker of apoptosis, in the myocardium 24 h postexercise. Microarray analysis of mouse myocardium identified 11 relevant apoptotic genes and several shifts in matrix remodeling transcripts over the postexercise window. Postexercise cardiomyocyte death was recapitulated in neonatal rat cardiomyocytes (NRCMs) by culturing cells in 2% plasma harvested from exercised rats. The increased cell death observed in exercise‐treated NRCMs was attenuated by β‐adrenergic blockade, but not antioxidant treatment. MSC survival, proliferation, and chemotaxis showed no significant differences between sedentary and exercise plasma conditions, despite increased IL‐6, TNF‐α, IL‐1β, and IFN‐γ secretions from MSCs treated with exercise plasma. NRCM survival was increased nearly 500% when cocultured with MSCs, but this effect was not altered under exercise plasma culture conditions. Our results suggest acute moderate‐intensity aerobic treadmill running in exercise‐naïve rodents induces temporal cardiomyocyte death due to plasma‐borne factors, namely, catecholaminergic stress. Even though exercise conditions prompt an inflammatory response in MSCs, the exercise milieu does not alter the MSC‐protective phenotype on cardiomyocytes.

Recovery of Inflammation, Cardiac, and Muscle Damage Biomarkers After Running a Marathon

“…Several studies indicate that, after intense physical effort, troponins are released, increasing their blood concentration; yet, despite this and the morphological (right atrial and ventricular dilation) and functional (reduced right ventricular ejection fraction) changes, no ischemic damage was observed for any cardiac chamber (43). The recent study by Arisi et al (2), performed with rodents, indicates a clear relationship between aerobic exercise (similar to that performed by marathon runners) and myocardial dysfunction and cardiomyocyte damage, but this is attributed to an increase in plasma catecholamines rather than to the increase of troponins.…”

Exercise-Induced Cardiac Troponin Elevations: From Underlying Mechanisms to Clinical Relevance

“…A study (n=18) of young mice (2-month-old) assessed apoptosis at baseline or immediately after 8, 24, 48, and 72 hours of running at 60% to 70% of V o 2 peak (n=3 animals per time point). 59 Exercise produced a transient 150% increase in the rate of myocardial apoptosis at 24 hours after exercise, in part, because of catecholaminergic, but not oxidative, stress. These findings suggest that, in animals, exercise acutely increases the rate of apoptosis, whereas apoptotic rates are reduced with chronic exercise training.…”

“…Exercise training reduces apoptotic rates [56][57][58] and increases cardiomyocyte growth and proliferation. 42,66 In contrast, (supra) physiological challenges to untrained animals, such as forced running, 59 volume overload, 61,63 or ischemia, 64 increase apoptosis with associated increases in cTn concentrations (Table 1). Whether these findings can be extrapolated to humans is not presently clear.…”

Enhancing myocardial repair with CardioClusters

“…A third enabling feature of CardioClusters is cardioprotective action, particularly under conditions of environmental stress. In vitro co-culture assays are an established protocol to assess the potential of candidate cell types to inhibit cardiomyocyte death from pro-apoptotic challenge 49,80 . Superior ability of Cardi-oClusters to blunt NRCM death relative to single parental cell types supports the rationale for culturing the mixed cell population together in a 3D configuration (Fig.…”