Regular exercise modulates cardiac mast cell activation in ovariectomized rats

Abstract

It is well accepted that regular exercise is a significant factor in the prevention of cardiac dysfunction; however, the cardioprotective mechanism is as yet not well defined. We have examined whether regular exercise can modulate the activity of cardiac mast cells (CMC) after deprivation of female sex hormones, as well as the density and percentage degranulation of mast cells, in ventricular tissue of ovariectomized (OVX) rats after an 11-week running program. A significant increase in CMC density with a greater percentage degranulation was induced after ovarian sex hormone deprivation. Increased CMC density was prevented by estrogen supplements, but not by regular training. To the contrary, increased CMC degranulation in the OVX rat heart was attenuated by exercise training, but not by estrogen supplement. These findings indicate a significant correlation between the degree of CMC degranulation and myocyte cross-section area. However, no change in the expression of inflammatory mediators, including chymase, interleukin-6, and interleukin-10, was detected. Taken together, these results clearly indicate one of the cardioprotective mechanisms of regular aerobic exercise is the modulation of CMC activation.

Comparison of exercise training and estrogen supplementation on mast cell-mediated doxorubicin-induced cardiotoxicity

“…To test the question, three potential methods were selected, including 1) estrogen supplementation, 2) exercise training, and 3) mast cell stabilizer administration. As we and others showed previously, estrogen supplementation prevented cardiac mast cell hyperactivation and cardiac contractile dysfunction in heart disease models (34,37,49). It is possible that estrogen supplementation may also abolish cardiac mast cell hyperactivation induced by doxorubicin.…”

“…Although COX-2 inhibitor showed medical benefit, it may cause other cardiovascular abnormalities (48). In recent years, the activation of cardiac mast cells has been studied (27,33,49). Previous studies primarily focused on the contribution of cardiac mast cells during pathological cardiac remodeling (27, 33).…”

“…To determine cardiac mast cell activation, 5-m-thick tissue slides were stained with 0.001 g/mL toluidine blue (49). Mast cell density was quantified by counting the number of mast cells per whole area of the tissue section.…”

“…A study demonstrated that short-term exercise training attenuated doxorubicin-induced cardiotoxicity (35). Our laboratory (49) previously demonstrated that chronic exercise at moderate intensity decreased cardiac mast cell degranulation in ovariectomized rats. We proposed that regular exercise could substitute for the use of hormone replacement therapy.…”

Beyond cardiomyocytes: Cellular diversity in the heart's response to exercise

“… Exercise model Outcome Animal model Voluntary wheel running (6 weeks) 120 Exercise increased hematopoietic stem cell quiescence; and reduced hematopoietic proliferation, myeloid and lymphoid colony production, and mobilization of circulating precursor immune cells, primarily via reduced leptin production in adipose tissue 7- to 8-week-old C57BL/6J male mice, leptin receptor knockout ( Lepr fl/fl mice) Wheel running (2 weeks, 1 h of daily exercise at a speed of 5.2 m/min) 126 Exercise upregulated PGC-1α and reduced cardiac (macrophage infiltration, iNOS and TNF-α expression) and systemic inflammation 8-month-old male diabetic mice Voluntary wheel running (12 weeks), ladder resistance training (3 times/week, 12 weeks), using a climbing ladder (90 cm, 1 cm grid, 80° incline, increased to 100% body weight) 125 Both forms of exercise prevented increase in circulating TNF-α, with decreases in tissue cytokine (TNF-α and IL-1β) mRNA expression in the heart, attenuating age-related chronic inflammation 38-week-old male SAMP1 mice Isoproterenol-induced cardiac stimulation, treadmill running (6 times/week, 4 weeks) 127 Isoproterenol increased IL-10 release via cardiac macrophage activation, producing heart failure phenotype; exercise reversed cardiac dysfunction and fibrosis. Beneficial effect was absent in macrophage/monocyte IL-10 knockout mice 6- to 8-week-old C57BL/6 male mice Wheel running (11 weeks), 133 treadmill training (9 weeks), 134 treadmill training (12 weeks, max of 21 m/min, 30 min twice a day, 5 days/week at 5.5% grade, 65%–75% max oxygen consumption) 135 All 3 exercise models reduced cardiac mast cell activation and degranulation in ovariectomized rats Treadmill training for 9 weeks reduced angiotensin II-induced cardiac fibrosis, mast cell degranulation and activation Treadmill training for 12 weeks did not reduce doxorubicin-induced cardiac dysfunction, but reduced mast cell activation 8- to 9-week-old Sprague-Dawley female rats, ovariectomized Abbreviations: IL = interleukin; iNOS = inducible nitric oxide synthase; Lepr fl/fl = leptin receptor flox/flox mice; PGC-1α = peroxisome proliferator-activated receptor-gamma coactivator -1alpha; SAMP1 = senescence-accelerated prone mouse 1; TNF-α = tumor necrosis factor-α. …”