Cardioprotective mechanism of FTY720 in ischemia reperfusion injury

Abstract

Cardioprotection is a very challenging area in the field of cardiovascular sciences. Myocardial damage accounts for nearly 50% of injury due to reperfusion, yet there is no effective strategy to prevent this to reduce the burden of heart failure. During last couple of decades, by combining genetic and bimolecular studies, many new drugs have been developed to treat hypertension, heart failure, and cancer. The use of percutaneous coronary intervention has reduced the mortality and morbidity of acute coronary syndrome dramatically. However, there is no standard therapy available that can mitigate cardiac reperfusion injury, which contributes to up to half of myocardial infarcts. Literature shows that the activation of sphingosine receptors, which are G protein-coupled receptors, induces cardioprotection both in vitro and in vivo. The exact mechanism of this protection is not clear yet. In this review, we discuss the mechanism of ischemia reperfusion injury and the role of the FDA-approved sphingosine 1 phosphate drug fingolimod in cardioprotection. Myocardial protection related to ischemia-reperfusion injuryIn recent decades, numerous studies have shown that the myocardial cells possess several coping mechanisms aiming to limit the damage of ischemia/reperfusion. These processes are not limited to the myocardium but Naseer Ahmed is the corresponding author.

FTY720 Attenuates LPS-Induced Inflammatory Bone Loss by Inhibiting Osteoclastogenesis via the NF-κB and HDAC4/ATF Pathways

“…FTY720 has been used for the clinical treatment of multiple sclerosis, and various studies have shown its potential for the treatment of bone loss disorders. The current findings, which focus on FTY720 as a regulator of S1P, suggest that it also affects osteoclastogenesis [43,44]. FTY720 had an inhibitory effect on OC formation in ligation-induced periodontitis in rats [45], and study of the role of FTY720 in animal models may provide new ideas for the treatment of periodontitis, which affects 11% of the global population and seriously affects human quality of life [46].…”

Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation Model

“…FTY720 regulates S1P 1 activities that are essential for lymphocyte migration and trafficking [ 8 ]. FTY720 is an effective anti-inflammatory and antioxidant agent, it inhibits the production of oxygen free radicals which reduce myocardial fibrosis and decreases the number of cardiomyocytes death [ 9 , 10 , 11 ]. From previous experimental studies it is evident that PARP (Poly(ADP-ribose) Polymerase) plays an active role in modulating pathophysiological condition of myocardial injury [ 12 ].…”