ABSTRACT
AIM: Myocardial ischemia (MI) is a leading cause of morbidity and mortality which makes the prevention and control of MI tremendously important. We aimed to explore the functional roles of ginsenoside (Gin) Rg1 in cardiomyocytes under hypoxia and to clarify underlying mechanisms. MAIN METHODS: Hypoxia-induced H9c2 cell injury was evaluated by alterations of cell viability, apoptosis and autophagy. Then, effects of Gin Rg1 on hypoxia-induced cell injury were measured. The activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathways as well as expression of hypoxia-inducible factor 1α (HIF-1α) was determined with or without addition of PI3K or mTOR inhibitor. Finally, the effects of Gin Rg1 on rat ischemia/reperfusion (I/R) injury and underlying mechanism were studied. KEY FINDINGS: First of all, hypoxia was identified to induce a decrease in cell viability and to increase cell apoptosis and autophagy. Then, these hypoxia-induced alterations were ameliorated by Gin Rg1, which had no effect on cell viability under normoxia. Subsequently, the phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathways as well as expression of HIF-1α were all elevated by Gin Rg1. Activation of the PI3K/AKT/mTOR pathways and HIF-1α expression were inhibited by PI3K inhibitor, and activation of mTOR pathway and HIF-1α expression were inhibited by mTOR inhibitor. More in vivo experiments proved that Gin Rg1 ameliorated rat I/R injury through activating the PI3K/AKT/mTOR pathways. SIGNIFICANCE: Gin Rg1 protected cardiomyocytes from hypoxia-induced cell injury by upregulating HIF-1α through activation of the PI3K/AKT/mTOR pathways.
Subject(s)
Ginsenosides/pharmacology , Myocardial Ischemia/prevention & control , Myocardial Reperfusion Injury/drug therapy , Myocytes, Cardiac/drug effects , Animals , Apoptosis/drug effects , Autophagy/drug effects , Cardiotonic Agents/pharmacology , Cell Hypoxia/drug effects , Cell Survival/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Male , Myocardial Reperfusion Injury/complications , Myocytes, Cardiac/pathology , Phosphatidylinositol 3-Kinase/metabolism , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , TOR Serine-Threonine Kinases/metabolism , Up-Regulation/drug effectsABSTRACT
OBJECTIVE: To determine whether the level of serum cardiac troponin T (cTnT) was increased in patients with congestive heart failure (CHF). METHODS: This study consisted of 265 patients with CHF and 75 healthy people. Serum cTnT was measured by electrochemiluminescence immunoassay using an Elecsys 1010 automatic analyzer. RESULTS: cTnT concentration was 0.181 +/- 0.536 ng/mL in CHF patients and 0.003 +/- 0.001 ng/mL in controls (P < 0.001). Patients were categorized according to the levels of heart function and left ventricular ejection fraction (LVEF). In the first group consisting of 105 patients with LVEF 35%, cTnT was 0.07 +/- 0.0 5 ng/mL (P < 0.01). In patients with NYHA class I, II, III and IV, cTnT values were 0.062 +/- 0.022 ng/mL, 0.113 +/- 0.121 mg/mL, 0.191 +/- 0.231 mg/ml and 0.384 +/- 0.211 mg/mL, respectively (class I vs class II P > 0.05, class II vs class III P < 0.01, class III vs class IV P < 0.01). A negative correlation was observed between serum cTnT concentration and LVEF in 265 patients with CHF (r = -0.493, P < 0.001). CONCLUSIONS: This study shows that the level of serum cTnT is increased in patients with CHF and that the increased level indicates the severity of CHF.