Bradykinin-(1-9) mitigates autophagy through upregulating PI3K/Akt in rats with myocardial infarction.

The cardioprotective mechanisms of bradykinin-(1-9) in myocardial infarction were unclear. We investigated the effect of bradykinin-(1-9) on cardiac function, fibrosis, and autophagy induced by myocardial infarction and identified the mechanisms involved. To investigate the cardioprotective effect of bradykinin-(1-9), various doses of bradykinin-(1-9), its B2 receptor blocker HOE140, or their combination were administered to rats via subcutaneous osmotic minipump implantation before myocardial infarction. After 2 days, myocardial infarction was induced by ligation of the left anterior descending coronary artery. After 2 weeks, echocardiographic measurements and euthanasia were performed. Bradykinin-(1-9) treatment attenuated left ventricular dysfunction, fibrosis, and autophagy in rats with myocardial infarction, which was partially reversed by HOE140 administration. Moreover, the downregulatory effect of bradykinin-(1-9) on autophagy was partially reversed by combination with the PI3K inhibitor LY294002. Thus, bradykinin-(1-9) inhibits myocardial infarction-induced cardiomyocyte autophagy by upregulating the PI3K/Akt pathway.

Antioxidant protein peroxiredoxin 6 suppresses the vascular inflammation, oxidative stress and endothelial dysfunction in angiotensin II-induced endotheliocyte.

Cardiovascular disease (CVD) states are associated with endothelial dysfunction (ED) and increased production of ROS in endothelial cells. The present study aimed to explore the protective effects of antioxidant protein peroxiredoxin 6 (PRDX6) on angiotensin II (AngII)­induced human umbilical vein endothelial cell (HUVEC) dysfunction. To investigate cell viability, levels of inflammatory molecules and proteins were assayed using the CCK-8 assay and evaluated by ELISA and Western blot. NO and ROS levels were determined by Griess assay and the fluorescent probe DCFH-DA. Cell migration capacity was assessed by Transwell assay. AngII decreased cell viability and PRDX6, upregulated the expression levels of TNF-α, IL-6, IL-1ß, LDH and MDA, stimulated ROS production, and reduced NO synthase, the expressions of eNOS, MnSOD, ICAM-1, VCAM-1, and activated the MAPK family of signaling proteins. However, the stimulatory effects of AngII on HUVECs were remarkably suppressed by PRDX6. Furthermore, mercaptosuccinate (MS; PRDX6 inhibitor) had similar effects as AngII in aggravating HUVECs damage. Conversely, these adverse events caused by AngII and MS were obviously reversed by ML3404 and SP600125. The present study indicated that PRDX6 overexpression inactivated p38 MAPK and JNK pathway through decrease AngII-induced inflammation, oxidative stress and endothelial dysfunction leading to attenuation of endothelial cell damage.