Engineered bioactive nanoparticles incorporated biofunctionalized ECM/silk proteins based cardiac patches combined with MSCs for the repair of myocardial infarction: In vitro and in vivo evaluations.

The development of cardiac patches by the combination of bioactive nano- and bio-materials with mesenchymal stem cells signifies an auspicious approach for the treatment of cardiac repair in myocardial infarction. In the present investigation, we study about the cardiac function of morphology improved gold nanoparticles combined with extracellular matrix/silk proteins for the cell proliferation and expansion of cardiomyocytes. The physico-chemical and morphological characteristics demonstrated that spherical and homogeneous Au particles are distributed on the matrix porous surface for providing favorable conductivity and biological influences in cardiac repair. The in vitro cell studies of prepared patches have established enhanced cell compatibility and retention of cardiomyocytes survival. The in vivo determinations imply that Au-ESF group decreases infarct size to 65% from 89% in control group. These developed cardiac patches can be highly suitable in the cardiac regeneration and offer new platform in cardiac tissue engineering.

Epicardial ganglionated plexi ablation increases the inducibility of ventricular tachyarrhythmias in a canine postmyocardial infarction model.

INTRODUCTION: Previous studies have shown that epicardial ganglionated plexi ablation (EGPA) could increase the risk of ventricular arrhythmias induced by acute myocardial ischemia. However, the long-term effect of EGPA in a canine postmyocardial infarction (MI) model is not well established. MATERIALS AND METHODS: Twenty mongrel dogs were randomly divided into two groups: an MI group (n = 10) and an EGPA group (EGPA plus MI, n = 10). EGPA was achieved by ablation of four major ganglion plexi and the ligament of Marshall. The electrocardiograph (ECG) parameters, ventricular effective refractory period (ERP), inducibility of tachyarrhythmias, and ventricular fibrillation threshold (VFT) were measured at baseline and after 8 weeks. Tyrosine hydroxylase (TH) and nerve growth factor (NGF) expression levels in the peri-infarcted zone were also determined by immunohistochemistry in both groups at the end of the study. RESULTS: No significant differences were found in electrophysiological parameters at the baseline between the two groups. At the end of the 8-week follow-up, however, the EGPA group was associated with a longer QT interval, corrected QT (QTc) interval and ventricular ERP, larger dispersion of QT, QTc, and ERP, and higher inducibility of tachyarrhythmia and VFT when compared to the MI group. In addition, the density of TH and NGF in the peri-infarcted zone was also significantly increased in the EGPA group in comparison to the MI group. CONCLUSIONS: After the 8-week follow-up, EGPA increased the ventricular arrhythmia inducibility in the canine post-MI model, likely by increasing ventricular electrophysiological instability and promoting ventricular sympathetic remodeling.

Rosuvastatin relieves myocardial ischemia/reperfusion injury by upregulating PPAR­Î³ and UCP2.

The present study aimed to investigate whether pretreatment with rosuvastatin (RS) can provide cardioprotection in a myocardial ischemia/reperfusion (MI/R) model. The protective effect of RS on myocardial oxygen­glucose deprivation/reperfusion (OGD/R) injury was also evaluated by upregulating peroxisome proliferator­activated receptor­Î³ (PPAR­Î³). In the present study, MI/R model was established and activities of superoxide dismutase (SOD), lactate dehydrogenase (LDH), creatine kinase­muscle/brain (CK­MB), malondialdehyde (MDA), and troponin I/T were measured. The infarct size was measured using Evans blue staining and cell viability was measured by MTT assay. Reactive oxygen species (ROS) levels were assessed by flow cytometry. Caspase­9, cytochrome c (cyt c), mitochondrial uncoupling protein 2 (UCP2) and PPAR­Î³ expression levels were detected by reverse transcription­quantitative polymerase chain reaction and western blotting. The results indicated that RS increased SOD activity, and decreased LDH, CK­MB, MDA and troponin I/T activities. The effect of RS was reversed by atractyloside (ATR). RS inhibited myocardial infarct size, downregulated expression of caspase­9 and cyt c and upregulated expression of UCP2 and PPAR­Î³ by inhibiting ATR. Furthermore, the results indicated that RS promoted cardiomyocyte viability, inhibited LDH release, reduced ROS production, decreased expression of caspase­9 and cyt c, and increased expression of UCP2 and PPAR­Î³ following OGD/R damage. Therefore, the present study demonstrated that RS protects primary myocardial cells against OGD/R injury by regulating PPAR­Î³ and UCP2. RS may be a promising therapeutic agent for treatment of MI/R injury.

Valsartan attenuates oxidative stress and NF-κB activation and reduces myocardial apoptosis after ischemia and reperfusion.

Myocardial apoptosis is primarily triggered during reperfusion. Various mechanisms are involved, including oxidative stress which activates the translocation of nuclear factor-kappa B (NF-κB) and stimulates the release of tumor necrosis factor-alpha (TNF-α). However, the relative contribution of the renin angiotensin system (RAS) to the development of myocardial apoptosis during reperfusion remains unknown. In the present study, we examined whether inhibition of RAS with Valsartan, an Angiotensin II 1 receptor (AT1) antagonist, could reduce apoptosis during reperfusion. We constructed a rat model of myocardial ischemia reperfusion injury. Rats were pretreated with Valsartan for 2 weeks, and then subjected to 30 min ischemia and 4h reperfusion. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Levels of malondialdehyde (MDA), superoxide dismutase (SOD), TNF-α, and caspase-3 were detected by ELISA. NF-κB, Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase expression was assessed by Western blot analysis. Valsartan inhibited apoptosis (TUNEL staining) in ischemic myocardium (P<0.05), consistent with reduced caspase-3 activity. Valsartan also inhibited of NF-κB translocation to nucleus (P<0.05), and decreased plasma TNF-α levels (P<0.05). Valsartan pretreatment suppressed MDA content and preserved SOD activity, consistent with reduced NADPH oxidase expression (P<0.01). These data provided substantial evidence that RAS was involved in NF-κB activation, mediated by AT1 dependent oxidative stress; thus, RAS might ultimately promote myocardial apoptosis during reperfusion pathogenesis.