Vitamin D attenuates myocardial ischemia–reperfusion injury by inhibiting inflammation via suppressing the RhoA/ROCK/NF‐ĸB pathway

Abstract

The aim of this study was to investigate the protective effects of vitamin D (VD) against myocardial ischemia–reperfusion (I/R) injury in hearts. An I/R injury model was induced by left coronary artery ligation in Sprague‐Dawley rats (in vivo) and Langendorff perfusion of isolated hearts (in vitro). The infarction areas were determined by triphenyltetrazolium chloride (TTC) staining. Changes in the ST segment, cardiac function, lactate dehydrogenase (LDH) activity, creatine kinase (CK) activity, inflammatory cytokine (interleukin‐6 (IL‐6), IL‐1β, and tumor necrosis factor‐α (TNF‐α)) levels and the RhoA/ROCK/NF‐ĸB pathway were tested in rats with I/R injury treated with or without VD. VD notably alleviated myocardial injury with decreased infarction areas and had a restorative effect on cardiac function, which was specifically manifested as a restored ST segment, increased myocardial contractility and increased coronary blood flow in the isolated hearts. The levels of CK and LDH were also suppressed by VD. In addition, VD significantly decreased the expression of inflammatory cytokines in rat sera and isolated hearts. The RhoA/ROCK/NF‐κB pathway in I/R‐injured rats was also obviously inhibited with VD treatment. The present study demonstrates that VD plays a protective role against myocardial injury by inhibiting inflammation through repressing the RhoA/ROCK/NF‐κB pathway.

Vitamin D Deficiency and the Risk of Cerebrovascular Disease

“…It down-regulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a transcription factor involved in inflammatory gene expression in lymphocytes [53], and can inhibit its activation by reducing DNA binding of NF-κB [54]. Vitamin D can also dampen inflammation after myocardial injury by inhibiting the RhoA/Rho-associated protein kinase (ROCK)/NF-κB pathway [55]. Furthermore, the VDR/RXR complex binds to the nuclear factor of activated T cells (NFAT) binding site of the IL-2 promoter and inhibits NFAT activity in T cells, thus blocking T cell proliferation [56] and leading to reduced expression of IL-17A [48].…”

From miRNA target gene network to miRNA function: miR-375 might regulate apoptosis and actin dynamics in the heart muscle via Rho-GTPases-dependent pathways

“…The role of small GTPases in the development of cardiovascular diseases is described [23] . In model animals with ischemia-reperfusion injury inhibitors of RhoA/ROCK signaling pathway demonstrate cardioprotective effect , which is realized through activation of MAPK and NFkB signaling pathways and reduction of Bcl-2 levels leading to a decrease in apoptotic activity of cells [24][25][26][27][28] .…”

Vitamin D may protect against multiple organ damage caused by COVID-19

“…IL-6 and TNF-α can decrease myocyte contractility precisely through the reduction of the systolic calcium level. The experimental study with myocardial ischemia-reperfusion model in rats showed that vitamin D (500 IU/5 day) alleviated myocardial injury considerably with reduced ST segment and infl ammatory cytokine (IL-6), IL-1β, TNF-α) levels (77). In another rat study, vitamin D prevented myocardial infarction by decreasing TNF-α and IL-6 level in isoprenalineinduced myocardial infarction (78).…”