Beta-glucan protects against isoproterenol-induced cardiac remodeling by regulating the ACE-AT1R axis and attenuates cardiac inflammation and apoptosis

Objective:To investigate the cardioprotective effect of beta-glucan against isoproterenol-induced cardiotoxicity in rats,and elucidate the underlying mechanism.Methods:Rats were orally pretreated with beta-glucan(40 mg/kg body weight)for 30 d,and isoproterenol(20 mg/100 g body weight)was administered on days 31 and 32.The effects of beta-glucan on markers of cardiac injury,hemodynamic changes,production of proinflammatory cytokines,and the corresponding mRNA expressions were evaluated.In addition,histological analysis was performed.Results:Pretreatment with beta-glucan prevented isoproterenol-induced cardiac injury by preserving the structural and functional integrity of the plasma membrane and attenuating the production of proinflammatory cytokines(NF-κB,TNF-α,IL-6,IL-1β,and IFN-γ)in the heart.Moreover,beta-glucan significantly downregulated the mRNA expression of ACE,AT1R,TNF-α,IL-6,NF-κB,caspase-3,TLR-4,and Bax,and upregulated Bcl-2 in the heart.At the same time,pretreatment with beta-glucan alleviated myocardial damage as reflected in a reduction in myonecrosis,edema,and erythrocyte extravasation with almost imperceptible inflammation.Conclusions:Beta-glucan can protect against isoproterenol-induced cardiotoxicity by attenuating cardiac inflammation and apoptosis and regulating the ACE-AT1R axis,thereby preventing cardiac remodeling.

A protease-activated receptor 1 antagonist protects against global cerebral ischemia/reperfusion injury after asphyxial cardiac arrest in rabbits

Cerebral ischemia/reperfusion injury is partially mediated by thrombin, which causes brain damage through protease-activated receptor 1（PAR1）. However, the role and mechanisms underlying the effects of PAR1 activation require further elucidation. Therefore, the present study investigated the effects of the PAR1 antagonist SCH79797 in a rabbit model of global cerebral ischemia induced by cardiac arrest. SCH79797 was intravenously administered 10 minutes after the model was established. Forty-eight hours later, compared with those administered saline, rabbits receiving SCH79797 showed markedly decreased neuronal damage as assessed by serum neuron specific enolase levels and less neurological dysfunction as determined using cerebral performance category scores. Additionally, in the hippocampus, cell apoptosis, polymorphonuclear cell infiltration, and c-Jun levels were decreased, whereas extracellular signal-regulated kinase phosphorylation levels were increased. All of these changes were inhibited by the intravenous administration of the phosphoinositide 3-kinase/Akt pathway inhibitor LY29004（3 mg/kg） 10 minutes before the SCH79797 intervention. These findings suggest that SCH79797 mitigates brain injury via anti-inflammatory and anti-apoptotic effects, possibly by modulating the extracellular signal-regulated kinase, c-Jun N-terminal kinase/c-Jun and phosphoinositide 3-kinase/Akt pathways.

Role of PTEN-less in cardiac injury,hypertrophy and regeneration

Cardiovascular diseases are the leading cause of death worldwide. Cardiomyocytes are capable of coordinatedcontractions, which are mainly responsible for pumping blood. When cardiac stress occurs, cardiomyocytesundergo transition from physiological homeostasis to hypertrophic growth, proliferation, or apoptosis. During theseprocesses, many cellular factors and signaling pathways participate. PTEN is a ubiquitous dual-specificityphosphatase and functions by dephosphorylating target proteins or lipids, such as PIP3, a second messenger in thePI3K/AKT signaling pathway. Downregulation of PTEN expression or inhibiting its biologic activity improves heartfunction, promotes cardiomyocytes proliferation, reduces cardiac fibrosis as well as dilation, and inhibits apoptosisfollowing ischemic stress such as myocardial infarction. Inactivation of PTEN exhibits a potentially beneficialtherapeutic effects against cardiac diseases. In this review, we summarize various strategies for PTEN inactivationand highlight the roles of PTEN-less in regulating cardiomyocytes during cardiac development and stress responses.