Perspectives for Forkhead box transcription factors in diabetic cardiomyopathy: Their therapeutic potential and possible effects of salvianolic acids

Abstract

Diabetic cardiomyopathy (DCM) is the primary cause of morbidity and mortality in diabetic cardiovascular complications, which initially manifests as cardiac hypertrophy, myocardial fibrosis, dysfunctional remodeling, and diastolic dysfunction, followed by systolic dysfunction, and eventually end with acute heart failure. Molecular mechanisms underlying these pathological changes in diabetic hearts are complicated and multifactorial, including but not limited to insulin resistance, oxidative stress, lipotoxicity, cardiomyocytes apoptosis or autophagy, inflammatory response, and myocardial metabolic dysfunction. With the development of molecular biology technology, accumulating evidence illustrates that members of the class O of Forkhead box (FoxO) transcription factors are vital for maintaining cardiomyocyte metabolism and cell survival, and the functions of the FoxO family proteins can be modulated by a wide variety of post-translational modifications including phosphorylation, acetylation, ubiquitination, arginine methylation, and O-glycosylation. In this review, we highlight and summarize the most recent advances in two members of the FoxO family (predominately FoxO1 and FoxO3a) that are abundantly expressed in cardiac tissue and whose levels of gene and protein expressions change as DCM progresses, with the goal of providing valuable insights into the pathogenesis of diabetic cardiovascular complications and discussing their therapeutic potential and possible effects of salvianolic acids, a natural product.

The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review

“…Its main function is to improve the viscous state of blood, with blood circulation, blood stasis, and good clinical tolerance ( 385 , 386 ). Current studies have shown that its mechanism of action is to inhibit the inflammatory response of endothelial cells, improve energy metabolism, promote vascular endothelial cell migration, and improve ischemia-reperfusion injury ( 380 , 387 , 388 ). Studies have shown that salvianolic acid can reduce the inflammatory factors (such as ICAM-1, IL-1β, IL-18 and TNF-α) in the cerebral cortex of the rat brain MCAO/R model, and reduce the apoptosis of cortical neurons.…”

Mesenchymal Stem Cell-Derived Exosomal Noncoding RNAs as Alternative Treatments for Myocardial Ischemia-Reperfusion Injury: Current Status and Future Perspectives

“…In addition to miR-182, miR-24-3p and miR-21-5p can be delivered by HUCMSC-EXOs and shift the polarization M1 macrophages to the M2 phenotype, not only suppressing the inflammatory response but also promoting the repair of diseased myocardial tissue [ 44 , 94 ]. Forkhead box protein O1 (FOXO1) is highly expressed in myocardial tissue and is closely associated with inflammatory signaling-related pathways [ 95 ]. BMSC-EXOs overexpressing miR-183-5p were recently shown to alleviate MIRI by downregulating FOXO1 expression [ 39 ].…”

RUNX3-activated apelin signaling inhibits cell proliferation and fibrosis in diabetic nephropathy by regulation of the SIRT1/FOXO pathway

“…A recent study reported that FOXO signaling pathway was enriched and activated in DN [ 22 ]. The acetylation of FOXO family was also demonstrated to be related with the progression of diabetic cardiomyopathy [ 23 ]. Nevertheless, the impact of Apelin on the FOXO signaling pathway remains unclear and requires further investigation.…”