Aerobic Exercise Ameliorates Myocardial Fibrosis via Affecting Vitamin D Receptor and Transforming Growth Factor-β1 Signaling in Vitamin D-Deficient Mice

Abstract

Myocardial fibrosis is a pathological phenomenon associated with cardiovascular disease (CVD) that plays a crucial role in the development of heart diseases. Vitamin D deficiency can promote the development of CVD and exercise plays a role in the treatment of CVD. This study aimed to explore the effects of 12-week aerobic exercise training on myocardial fibrosis in vitamin D-deficient mice. A vitamin D-deficient mouse model was induced by a vitamin D-deficient (0 IU Vitamin D3/kg) diet. Twenty-four C57BL/6J male mice were randomly divided into three groups: a control sedentary group (CONS, n = 8), a vitamin D-deficient sedentary group (VDDS, n = 8), and a vitamin D-deficient exercise group (VDDE, n = 8) which was aerobically trained for 12 weeks. The results showed that the serum 25-hydroxyvitamin D [25(OH)D] levels of the VDDS group were <50 nmol/L, which was significantly lower than that of the CONS group. Compared with the CONS group, the VDDS group showed cardiac dysfunction and significant fibrosis, together with lower vitamin D receptor (VDR) mRNA and protein expression levels, higher mRNA expression levels of profibrotic and inflammatory factors, and higher transforming growth factor-β1 (TGF-β1) and phospho-Smad2/3 (P-Smad2/3) protein expression levels. Serum 25(OH)D levels in the VDDE group were significantly higher than those in the VDDS group. Compared with the VDDS group, the VDDE group showed improved cardiac function and alleviated myocardial fibrosis. Meanwhile, the VDDE group had significantly higher VDR mRNA and protein expression levels; lower mRNA expression levels of profibrotic and inflammatory factors; and lower TGF-β1 and P-Smad2/3 protein expression levels. In conclusion, aerobic exercise training remains a promising intervention for treating myocardial fibrosis in vitamin D deficiency.

Exercise improves cardiac fibrosis by stimulating the release of endothelial progenitor cell-derived exosomes and upregulating miR-126 expression

“…As an important pathological process of heart failure, can exercise have a good regulatory effect on cardiac fibrosis? We found that aerobic training plays an important role in attenuating cardiac fibrosis caused by vitamin D deficiency through its inhibitory effect on fibrotic factors and pathways (82), another study found that aerobic training combined with resistance exercise and vitamin D supplementation could reduce cardiac fibrosis by inhibiting TGF-β/Smads signaling pathway and regulating collagen fiber expression (83), running training, the most maneuverable aerobic exercise, still has a good improvement effect on cardiac fibrosis, for example, Ang II-induced cardiac fibrosis was attenuated in mice trained by running for 6 weeks (84), in a rat model of arthritis, individualized running training not only reduced fibrosis, but also alleviated the severity of arthritis (85). Moreover, exercise training can modulates the fibroblasts FGF21 factor and TGF-β1-Smad2/3-MMP2/9 signaling pathway to attenuate collagen fiber production (86).…”

Effects of Vitamin D3 Supplementation and Aerobic Training on Autophagy Signaling Proteins in a Rat Model Type 2 Diabetes Induced by High-Fat Diet and Streptozotocin

“…It has been shown that activation of VDR leads to increased AMPK and decreased mTOR, two key regulators of autophagy [ 87 ]. Recently, it has been reported that aerobic training reduces cardiac fibrosis through increased expression of VDR due to vitamin D3 supplementation [ 88 ].…”

The pharmacological role of Ginsenoside Rg3 in liver diseases: A review on molecular mechanisms

“…Inflammatory cells are responsible for hepatic inflammation and secrete proinflammatory and profibrotic factors, such as TGF-β1. This factor, in turn, activates HSCs, leading to the formation of an autocrine-positive feedback loop that further aggravates hepatic fibrogenesis [ [60] , [61] , [62] ]. Despite great progress in understanding the etiology of liver fibrosis, specific treatments are still lacking.…”