A novel small molecule compound VCP979 improves ventricular remodeling in murine models of myocardial ischemia/reperfusion injury

Abstract

Persistent ventricular remodeling following myocardial ischemia/reperfusion (MI/R) injury results in functional decompensation and eventual progression to heart failure. VcP979, a novel small-molecule compound developed in-house, possesses anti-inflammatory and anti-fibrotic activities. In the present study, no significant pathological effect was observed following the administration of VCP979 on multiple organs in mice and no difference of aspartate transaminase/alanine aminotransferase/lactate dehydrogenase levels was found in murine serum. Treatment with VcP979 ameliorated cardiac dysfunction, pathological myocardial fibrosis and hypertrophy in murine MI/R injury models. The administration of VCP979 also inhibited the infiltration of inflammatory cells and the pro-inflammatory cytokine expression in hearts post MI/R injury. Further results revealed that the addition of VcP979 prevented the primary neonatal cardiac fibroblasts (NCFs) from Angiotensin II (Ang II)-induced collagen synthesis and neonatal cardiac myocytes (NcMs) hypertrophy. In addition, VcP979 attenuated the activation of p38-mitogen-activated protein kinase in both Ang II-induced NCFs and hearts subjected to MI/R injury. These findings indicated that the novel small-molecule compound VcP979 can improve ventricular remodeling in murine hearts against MI/R injury, suggesting its potential therapeutic function in patients subjected to MI/R injury.

Intramyocardial injected human umbilical cord-derived mesenchymal stem cells (HucMSCs) contribute to the recovery of cardiac function and the migration of CD4+ T cells into the infarcted heart via CCL5/CCR5 signaling

“…Mice were anesthetized with 2% isoflurane inhalation and analyzed using a Vevo 2100 high-resolution imaging system with a 30-MHz linear transducer (FUJIFILM Visual-Sonics, Inc.) as previously described [ 11 ]. We acquired and analyzed the cardiac function of each group through long-axis scans using M-mode images including left ventricular ejection function (LVEF), left ventricular fractional shortening (LVFS), left ventricular end diastolic/systolic volume (LVEDV/LVESV) and left ventricular end diastolic/systolic diameter (LVEDD/LVESD) both on day 7 and 28.…”

Intramyocardial Injected Human Umbilical Cord-Derived Mesenchymal Stem Cells (Hucmscs ) Contribute to the Recovery of Cardiac Function and the Migration of CD4+ T Cells into the Infarcted Heart via CCL5/CCR5 Signaling

“…Mice were anesthetized with 2% iso urane inhalation and analyzed using a Vevo 2100 high-resolution imaging system with a 30-MHz linear transducer (FUJIFILM Visual-Sonics, Inc.) as previously described [11]. We acquired and analyzed the cardiac function of each group through long-axis scans using M-mode images including left ventricular ejection function (LVEF), left ventricular fractional shortening (LVFS), left ventricular end diastolic/systolic volume (LVEDV/LVESV) and left ventricular end diastolic/systolic diameter (LVEDD/LVESD) on day 7 and 28.…”

Propionate alleviates myocardial ischemia-reperfusion injury aggravated by Angiotensin II dependent on caveolin-1/ACE2 axis through GPR41

“…Li et al revealed that losartan, an angiotensin II (Ang II) receptor blocker acting on the Ang II type-1 receptor (AT1R) subtype, protects against myocardial I/R injury via vascular integrity preservation [42]. Liu et al showed that inhibiting Ang II can improve ventricular remodeling in murine models of myocardial I/R injury [43]. These indicate that maintaining a steady state of Ang II levels is a potential strategy for treating myocardial I/R injury.…”