Here, we investigate for the first time in vivo the cardioprotective potentials of two unique Cx43 structural-mimetic peptides (Cx43MPs) presumed specific blockers of Cx43Hc, Gap26 and Gap27, when injected intravenously using a rat model of myocardial infarction.Sprague Dawley rats were utilized.
Effects of Radix et Rhizoma Rhodiolae Kirilowii on expressions of von Willebrand factor, hypoxia-inducible factor 1 and vascular endothelial growth factor in myocardium of rats with acute myocardial infarction.
Two weeks after MI, both HIF-1alpha and HIF-2alpha mRNA were moderately increased in the infarcted left ventricle and noninfarcted left ventricle; HIF-2alpha amplification was also detected in areas of the interventricular septum and the right ventricle.
Gross pathology showed around 26% infarction at 24 h. Histopathology revealed death of cardiomyocytes with blood vessel congestion at the end of 24 h, inflammatory infiltrate at 48 h, fibrotic scar by 96 h and collagen deposition by 192 h. Acute myocardial infarction biomarkers such as Cardiac Troponin T, Creatine Kinase MB and NT pro BNP were shown to be elevated by 4 h. ECG showed an ST segment elevation by 96 h. This cryoinfarction model was suitable to study changes taking place during acute myocardial infarction in humans.
Our current findings support the premise that HO-1 transduced by MSCs can induce angiogenic effects and improve heart function after acute myocardial infarction.
By day 28, increases in ACE (P = 0.005) and ACE2 (P = 0.006) mRNA were also seen in the viable myocardium of MI rats compared with myocardium of control rats.
Myocardial expression of endothelin-2 is altered reciprocally to that of endothelin-1 during ischemia of cardiomyocytes in vitro and during heart failure in vivo.
In conclusion, in a rat model of myocardial infarction, the thrombosis, inflammatory reaction and tissue damage-related indicators GMP-140, hs-CRP, IL-6 and MMP-9 increased significantly, while t-PA and TIMP-1 decreased dynamically.
Treatment with irbesartan plus carvedilol reduced the expression of TF and TFPI mRNA and protein after MI in rats, and combined treatment with both agents had greater effects than the single agents alone.
In addition, decreased mitochondrial anti-oxidase content, Phase II enzyme (except heme oxygenase-1) expression and mitochondrial biogenesis were observed in the post-MI rats as well as reduced protein levels of the regulators Nrf2 and p-AMPK and suppression of SIRT3 levels and PI3-K/Akt signalling.
This is the first report showing that the expression of p22-phox and gp91-phox, essential components of NADPH oxidase, are increased in the infarcted sites after myocardial infarction.
With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations.
Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia.