Enhanced Cardiac S100A1 Expression Improves Recovery from Global Ischemia-Reperfusion Injury

Abstract

Gene-targeted therapy with the inotropic Ca2 + -sensor protein S100A1 rescues contractile function in post-ischemic heart failure and is being developed towards clinical trials. Its proven beneficial effect on cardiac metabolism and mitochondrial function suggests a cardioprotective effect of S100A1 in myocardial ischemia-reperfusion injury (IRI). Fivefold cardiomyocyte-specific S100A1 overexpressing, isolated rat hearts perfused in working mode were subjected to 28 min ischemia (37 °C) followed by 60 min reperfusion. S100A1 overexpressing hearts showed superior hemodynamic recover: Left ventricular pressure recovered to 57 ± 7.3% of baseline compared to 51 ± 4.6% in control (p = 0.025), this effect mirrored in LV work and dP/dt(max). Troponin T and lactate dehydrogenase was decreased in the S100A1 group, as well as FoxO pro-apoptotic transcription factor, indicating less tissue necrosis, whereas phosphocreatine content was higher after reperfusion. This is the first report of a cardioprotective effect of S100A1 overexpression in a global IRI model.

Systematic Understanding of the Mechanism of Baicalin against Ischemic Stroke through a Network Pharmacology Approach

“…Nuclear transcription factor FOXO was thought to be involved in neuronal apoptotic signal transduction induced by hypoxic ischemia in the developing brain [44]. Indeed, FOXO is also associated with ischemia-reperfusion injury in various tissues including the heart [45] and liver [46]. Only one study investigated the relationship between baicalin and FOXO activation, implicating treatment with baicalin influenced phosphorylation/acetylation of FoxO1 via PI3K/Akt by insulin in aged rats [46].…”

Association between serum S100A1 level and Global Registry of Acute Coronary Events score in patients with non-ST-segment elevation acute coronary syndrome

“… 20 , 21 Jungi et al. 22 reported that S100A1 could exert a cardioprotective effect on global ischemia-reperfusion injury. The present study showed that the serum concentration of S100A1 was significantly increased in patients with NSTE-ACS and was closely related to the short-term prognosis.…”

“…[17][18][19] Some researchers have studied whether the S100A1 level can be used to diagnose acute myocardial ischemia, and they found that a longer duration of myocardial ischemia was associated with a higher level of serum S100A1. 20,21 Jungi et al 22 reported that S100A1 could exert a cardioprotective effect on global ischemia- reperfusion injury. The present study showed that the serum concentration of S100A1 was significantly increased in patients with NSTE-ACS and was closely related to the short-term prognosis.…”

Novel Molecular Targets Participating in Myocardial Ischemia-Reperfusion Injury and Cardioprotection

“…A transcriptional regulation study through bioinformatics revealed that four potential hypoxia-inducible factor-1 alpha (HIF-1 α )-binding motifs on the promoter of renalase (an enzyme elevated during MIRI that can metabolize catecholamine) are novel loci involved in cardioprotection against MIRI [112]. S100A1 [113] and S100A6 [11], members of the S100 family protein containing EF-hand and Ca 2+ -binding motifs, as well as Annexin-5 (a member of the Annexin family containing Ca 2+ -dependent phospholipid binding motifs) [12], might regulate several intrinsic apoptosis pathways involved in MIRI, generating a smaller infarct size and improving the systolic function of the left ventricle. Similarly, the innovative roles and action sites of several cardioprotective genes against MIRI associated with intracellular homeostasis and antiapoptosis have been signposted using bioinformatic methods, such as STAT3 [114], GSTP [115], SGLT1 [116], BCL2 [117], and SERCA2 [118].…”