cardioprotection

Cardioprotection encompasses several regimens that have shown to preserve function and viability of cardiac muscle cell tissue subjected to ischemic insult or reoxygenation.

Cardioprotection includes strategies that are implemented:

• before an ischemic event (preconditioning, PC),
• during an ischemic event (perconditioning, PerC),
• after the event and during reperfusion (postconditioning, PostC).{{cite journal|last1=Vinten-Johansen|first1=J|last2=Shi|first2=W|date=2011|title=Perconditioning and postconditioning: current knowledge, knowledge gaps, barriers to adoption, and future directions.|journal=Journal of Cardiovascular Pharmacology and Therapeutics|volume=16|issue=3–4|pages=260–6|doi=10.1177/1074248411415270|pmid=21821526|s2cid=20432309}}

These strategies can be further stratified by performing the intervention locally or remotely, creating classes of conditioning known as remote ischemic PC (RIPC), remote ischemic PostC and remote ischemic PerC. Classical (local) preconditioning has an early phase with an immediate onset lasting 2–3 hours that protects against myocardial infarction.{{cite journal|last1=Murry|first1=CE|last2=Jennings|first2=RB|last3=Reimer|first3=KA|title=Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.|journal=Circulation|date=November 1986|volume=74|issue=5|pages=1124–36|pmid=3769170|doi=10.1161/01.cir.74.5.1124|doi-access=free}} The early phase involves post-translational modification of preexisting proteins, brought about by the activation of G protein-coupled receptors as well as downstream MAPK's and PI3/Akt. These signaling events act on the ROS-generating mitochondria, activate PKCε and the Reperfusion Injury Salvage Kinase (RISK) pathway, preventing mitochondrial permeability transition pore (MTP) opening.{{cite journal|last1=Hausenloy|first1=DJ|last2=Yellon|first2=DM|title=New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway.|journal=Cardiovascular Research|date=15 February 2004|volume=61|issue=3|pages=448–60|pmid=14962476|doi=10.1016/j.cardiores.2003.09.024|doi-access=free}} The late phase with an onset of 12–24 hours that lasts 3–4 days and protects against both infarction and reversible postischemic contractile dysfunction, termed myocardial stunning.{{cite journal|last1=Kuzuya|first1=T|last2=Hoshida|first2=S|last3=Yamashita|first3=N|last4=Fuji|first4=H|last5=Oe|first5=H|last6=Hori|first6=M|last7=Kamada|first7=T|last8=Tada|first8=M|title=Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia.|journal=Circulation Research|date=June 1993|volume=72|issue=6|pages=1293–9|pmid=8495557|doi=10.1161/01.res.72.6.1293|doi-access=free}}{{cite journal|last1=Marber|first1=MS|last2=Latchman|first2=DS|last3=Walker|first3=JM|last4=Yellon|first4=DM|title=Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction.|journal=Circulation|date=September 1993|volume=88|issue=3|pages=1264–72|pmid=8353888|doi=10.1161/01.cir.88.3.1264|doi-access=free}}{{cite journal|last1=Bolli|first1=R|title=The late phase of preconditioning.|journal=Circulation Research|date=24 November 2000|volume=87|issue=11|pages=972–83|pmid=11090541|doi=10.1161/01.res.87.11.972|doi-access=free}} This phase involves the synthesis of new cardioprotective proteins stimulated by nitric oxide (NO), Reactive oxygen species (ROS) and adenosine acting on kinases such as PKCε and Src, which in turn activate gene transcription and upregulation of late PC molecular players (e.g., antioxidant enzymes, iNOS).{{cite journal|last1=Bolli|first1=R|last2=Li|first2=QH|last3=Tang|first3=XL|last4=Guo|first4=Y|last5=Xuan|first5=YT|last6=Rokosh|first6=G|last7=Dawn|first7=B|title=The late phase of preconditioning and its natural clinical application--gene therapy.|journal=Heart Failure Reviews|date=December 2007|volume=12|issue=3–4|pages=189–99|pmid=17541820|doi=10.1007/s10741-007-9031-4|pmc=3652384}}

A role for PKCε in more contemporary cardioprotection strategies including RIPC,{{cite journal|last1=Przyklenk|first1=K|last2=Bauer|first2=B|last3=Ovize|first3=M|last4=Kloner|first4=RA|last5=Whittaker|first5=P|title=Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion.|journal=Circulation|date=March 1993|volume=87|issue=3|pages=893–9|pmid=7680290|doi=10.1161/01.cir.87.3.893|doi-access=free}} local PostC,{{cite journal|last1=Zhao|first1=ZQ|last2=Corvera|first2=JS|last3=Halkos|first3=ME|last4=Kerendi|first4=F|last5=Wang|first5=NP|last6=Guyton|first6=RA|last7=Vinten-Johansen|first7=J|title=Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning.|journal=American Journal of Physiology. Heart and Circulatory Physiology|date=August 2003|volume=285|issue=2|pages=H579-88|pmid=12860564|doi=10.1152/ajpheart.01064.2002}} and remote PostC{{cite journal|last1=Kerendi|first1=F|last2=Kin|first2=H|last3=Halkos|first3=ME|last4=Jiang|first4=R|last5=Zatta|first5=AJ|last6=Zhao|first6=ZQ|last7=Guyton|first7=RA|last8=Vinten-Johansen|first8=J|title=Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors.|journal=Basic Research in Cardiology|date=September 2005|volume=100|issue=5|pages=404–12|pmid=15965583|doi=10.1007/s00395-005-0539-2|s2cid=34810140}} have been either demonstrated or suggested. It was shown that PKCε translocates from the cytosolic to the particulate fraction upon RIPC induction and that the protection conferred by RIPC can be inhibited with the PKC inhibitor chelerythrine{{cite journal|last1=Wolfrum|first1=S|last2=Schneider|first2=K|last3=Heidbreder|first3=M|last4=Nienstedt|first4=J|last5=Dominiak|first5=P|last6=Dendorfer|first6=A|title=Remote preconditioning protects the heart by activating myocardial PKCepsilon-isoform.|journal=Cardiovascular Research|date=15 August 2002|volume=55|issue=3|pages=583–9|pmid=12160956|doi=10.1016/s0008-6363(02)00408-x|doi-access=}}{{cite journal|last1=Weinbrenner|first1=C|last2=Nelles|first2=M|last3=Herzog|first3=N|last4=Sárváry|first4=L|last5=Strasser|first5=RH|title=Remote preconditioning by infrarenal occlusion of the aorta protects the heart from infarction: a newly identified non-neuronal but PKC-dependent pathway.|journal=Cardiovascular Research|date=15 August 2002|volume=55|issue=3|pages=590–601|pmid=12160957|doi=10.1016/s0008-6363(02)00446-7|doi-access=free}} Similarly, in models of local PostC, phosphorylation and activation of PKCε has been shown to be induced and PKCε inhibition attenuated the beneficial effects of these regimens.{{cite journal|last1=Zatta|first1=AJ|last2=Kin|first2=H|last3=Lee|first3=G|last4=Wang|first4=N|last5=Jiang|first5=R|last6=Lust|first6=R|last7=Reeves|first7=JG|last8=Mykytenko|first8=J|last9=Guyton|first9=RA|last10=Zhao|first10=ZQ|last11=Vinten-Johansen|first11=J|title=Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling.|journal=Cardiovascular Research|date=1 May 2006|volume=70|issue=2|pages=315–24|pmid=16443207|doi=10.1016/j.cardiores.2005.11.030|doi-access=free}}{{cite journal|last1=Philipp|first1=S|last2=Yang|first2=XM|last3=Cui|first3=L|last4=Davis|first4=AM|last5=Downey|first5=JM|last6=Cohen|first6=MV|title=Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade.|journal=Cardiovascular Research|date=1 May 2006|volume=70|issue=2|pages=308–14|pmid=16545350|doi=10.1016/j.cardiores.2006.02.014}} A recent study showed that blocking Hsp90 function with geldanamycin inhibits PostC protection and PKCε translocation.{{cite journal|last1=Zhong|first1=GQ|last2=Tu|first2=RH|last3=Zeng|first3=ZY|last4=Li|first4=QJ|last5=He|first5=Y|last6=Li|first6=S|last7=He|first7=Y|last8=Xiao|first8=F|title=Novel functional role of heat shock protein 90 in protein kinase C-mediated ischemic postconditioning.|journal=The Journal of Surgical Research|date=15 June 2014|volume=189|issue=2|pages=198–206|pmid=24742623|doi=10.1016/j.jss.2014.01.038}} Additional studies are required to investigate a role for PKCε in remote PostC and PerC, as this has not been conclusively demonstrated.

Cardioprotective strategies are studied for their potential to reduce heart damage in conditions like heart attack or surgery involving reperfusion.

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Category:Heart

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