7 research outputs found
Data on necrotic and apoptotic cell death in acute myocardial ischemia/reperfusion injury: the effects of CaMKII and angiotensin AT1 receptor inhibition
Content of particular proteins indicating cellular injury due to apoptosis and necrosis has been investigated in ischemic/reperfused (IR) hearts and ischemic/reperfused hearts treated with CaMKII inhibitor and/or AT1 receptor inhibitor. This data article provides information in support of the original research article “Oxidative activation of CaMKIIδ in acute myocardial ischemia/reperfusion injury: a role of angiotensin AT1 receptor-NOX2 signaling axis” [1]. Keywords: Myocardial ischemia/reperfusion injury, CaMKII inhibition, AT1 receptor blockade, Apoptosis, Necrosi
Oxidative activation of CaMKIIdelta in acute myocardial ischemia/reperfusion injury: A role of angiotensin AT receptor-NOX2 signaling axis
During ischemia/reperfusion (IR), increased activation of angiotensin AT1 receptors recruits NADPH oxidase 2 (NOX2) which contributes to oxidative stress. It is unknown whether this stimulus can induce oxidative activation of Ca2+/calmodulin-dependent protein kinase IIdelta (CaMKIIdelta) leading into the aggravation of cardiac function and whether these effects can be prevented by angiotensin AT1 receptors blockade. Losartan, a selective AT1 blocker, was used. Its effects were compared with effects of KN-93, an inhibitor of CaMKIIdelta. Global IR was induced in Langendorff-perfused rat hearts. Protein expression was evaluated by immunoblotting and lipoperoxidation was measured by TBARS assay. Losartan improved LVDP recovery by 25%; however, it didn't reduce reperfusion arrhythmias. Oxidized CaMKIIdelta (oxCaMKIIdelta) was downregulated at the end of reperfusion compared to before ischemia and losartan did not change these levels. Phosphorylation of CaMKIIdelta mirrored the pattern of changes in oxCaMKIIdelta levels. Losartan did not prevent the higher lipoperoxidation due to IR and did not influence NOX2 expression. Inhibition of CaMKII ameliorated cardiac IR injury; however, this was not accompanied with changes in the levels of either active form of CaMKIIdelta in comparison to the angiotensin AT1 receptor blockade. In spite of no changes of oxCaMKIIdelta, increased cardiac recovery of either therapy was abolished when combined together. This study showed that oxidative activation of CaMKIIdelta is not elevated at the end of R phase. NOX2-oxCAMKIIdelta signaling is unlikely to be involved in cardioprotective action of angiotensin AT1 receptor blockade which is partially abolished by concomitant CaMKII inhibition
Non-invasive approach to mend the broken heart: is “remote conditioning” a promising strategy for application in humans?
Currently, there are no satisfactory interventions to protect the heart against the detrimental effects of ischemia-reperfusion injury. Although ischemic preconditioning (PC) is the most powerful form of intrinsic cardioprotection, its application in humans is limited to planned interventions, due to its short duration and technical requirements. However, many organs/tissues are capable of producing â remoteâ PC (RPC) when subjected to brief bouts of ischemia-reperfusion. RPC was first described in the heart where brief ischemia in one territory led to protection in other area. Later on, RPC started to be used in patients with acute myocardial infarction, albeit with ambiguous results. It is hypothesized that the connection between the signal triggered in remote organ and protection induced in the heart can be mediated by humoral and neural pathways as well as via systemic response to short sublethal ischemia. However, although RPC has a potentially important clinical role, our understanding of the mechanistic pathways linking the local stimulus to the remote organ remains incomplete. Nevertheless, RPC appears as a cost-effective and easily performed intervention. Elucidation of protective mechanisms activated in the remote organ may have therapeutic and diagnostic implications in the management of myocardial ischemia and lead to development of pharmacological RPC mimetics.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author