Trigger, Signaling Mechanism and End Effector of Cardioprotective Effect of Remote Postconditioning of Heart

Author(s): Leonid N. Maslov*, Sergey Y. Tsibulnikov, Ekaterina S. Prokudina, Sergey V. Popov, Alla A. Boshchenko, Nirmal Singh, Yi Zhang, Peter R. Oeltgen.

Journal Name: Current Cardiology Reviews

Volume 15 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

The hypothetical trigger of remote postconditioning (RPost) of the heart is the highmolecular weight hydrophobic peptide(s). Nitric oxide and adenosine serve as intermediaries between the peptide and intracellular structures. The role of the autonomic nervous system in RPost requires further study. In signaling mechanism RPost, kinases are involved: protein kinase C, PI3, Akt, JAK. The hypothetical end effector of RPost is aldehyde dehydrogenase-2, the transcription factors STAT, Nrf2, and also the BKCa channel.

Keywords: Heart, ischemia, reperfusion, remote postconditioning, humoral factor, autonomic nervous system, signaling, end effector.

[1]
Menees DS, Peterson ED, Wang Y, et al. Door-to-balloon time and mortality among patients undergoing primary PCI. N Engl J Med 2013; 369(10): 901-9.
[2]
McCartney PJ, Berry C. Redefining successful primary PCI. Eur Heart J Cardiovasc Imaging 2019; 20(2): 133-5.
[3]
Kerendi F, Kin H, Halkos ME, et al. Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors. Basic Res Cardiol 2005; 100(5): 404-12.
[4]
Cohen MV, Downey JM. Signalling pathways and mechanisms of protection in pre- and postconditioning: Historical perspective and lessons for the future. Br J Pharmacol 2015; 172(8): 1913-32.
[5]
Heusch G. Molecular basis of cardioprotection: Signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 2015; 116(4): 674-99.
[6]
Heusch G, Rassaf T. Time to give up on cardioprotection? A critical appraisal of clinical studies on ischemic pre-, post-, and remote conditioning. Circ Res 2016; 119(5): 676-95.
[7]
Heusch G, Gersh BJ. The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: A continual challenge. Eur Heart J 2017; 38(11): 774-84.
[8]
Hausenloy DJ, Yellon DM. Ischaemic conditioning and reperfusion injury. Nat Rev Cardiol 2016; 13(4): 193-209.
[9]
Iliodromitis EK, Cohen MV, Dagres N, Andreadou I, Kremastinos DT, Downey JM. What is wrong with cardiac conditioning? We may be shooting at moving targets. J Cardiovasc Pharmacol Ther 2015; 20(4): 357-69.
[10]
Davies WR, Brown AJ, Watson W, et al. Remote ischemic preconditioning improves outcome at 6 years after elective percutaneous coronary intervention: the CRISP stent trial long-term follow-up. Circ Cardiovasc Interv 2013; 6(3): 246-51.
[11]
Giblett JP, Hoole SP. Remote ischemic conditioning in elective PCI? J Cardiovasc Pharmacol Ther 2017; 22(4): 310-5.
[12]
Davidson SM, Riquelme JA, Zheng Y, Vicencio JM, Lavandero S, Yellon DM. Endothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning. Sci Rep 2018; 8(1): 15885.
[13]
Gao Q, Hu J, Hu J, et al. Calcium activated potassium channel and protein kinase C participate in the cardiac protection of remote post conditioning. Pak J Pharm Sci 2013; 26(2): 285-90.
[14]
Li CM, Zhang XH, Ma XJ, Luo M. Limb ischemic postconditioning protects myocardium from ischemia-reperfusion injury. Scand Cardiovasc J 2006; 40(5): 312-7.
[15]
Andreka G, Vertesaljai M, Szantho G, et al. Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs. Heart 2007; 93(6): 749-52.
[16]
Fang J, Chen L, Wu L, Li W. Intra-cardiac remote ischemic post-conditioning attenuates ischemia-reperfusion injury in rats. Scand Cardiovasc J 2009; 43(6): 386-94.
[17]
Gritsopoulos G, Iliodromitis EK, Zoga A, et al. Remote postconditioning is more potent than classic postconditioning in reducing the infarct size in anesthetized rabbits. Cardiovasc Drugs Ther 2009; 23(3): 193-8.
[18]
Tang Y, Mennander A, Oksala N, et al. Postconditioning and remote postconditioning of ischemic rat cardiac grafts. Eur Surg Res 2010; 45(1): 1-8.
[19]
Tang YH, Xu JJ, Li JX, Cheng XS. Remote postconditioning induced by brief pulmonary ischemia and reperfusion attenuates myocardial reperfusion injury in rabbits. Chin Med J (Engl) 2011; 124(11): 1683-8.
[20]
Basalay M, Barsukevich V, Mastitskaya S, et al. Remote ischaemic pre- and delayed postconditioning - similar degree of cardioprotection but distinct mechanisms. Exp Physiol 2012; 97(8): 908-17.
[21]
Yu Y, Jia XJ, Zong QF, et al. Remote ischemic postconditioning protects the heart by upregulating ALDH2 expression levels through the PI3K/Akt signaling pathway. Mol Med Rep 2014; 10(1): 536-42.
[22]
Ren HM, Xie RQ, Cui W, Liu F, Hu HJ, Lu JC. Effects of rabbit limbs ischemia/ reperfusion on myocardial necrosis and apoptosis. Can J Appl Physiol 2012; 28(4): 323-7.
[23]
Zhu SB, Liu Y, Zhu Y, et al. Remote preconditioning, perconditioning, and postconditioning: a comparative study of their cardio-protective properties in rat models. Clinics (São Paulo) 2013; 68(2): 263-8.
[24]
Zhang JQ, Wang Q, Xue FS, et al. Ischemic preconditioning produces more powerful anti-inflammatory and cardioprotective effects than limb remote ischemic postconditioning in rats with myocardial ischemia-reperfusion injury. Chin Med J (Engl) 2013; 126(20): 3949-55.
[25]
Takagi H, Matsui Y, Sadoshima J. The role of autophagy in mediating cell survival and death during ischemia and reperfusion in the heart. Antioxid Redox Signal 2007; 9(9): 1373-82.
[26]
Sybers HD, Ingwall J, DeLuca M. Autophagy in cardiac myocytes. Recent Adv Stud Cardiac Struct Metab 1976; 12: 453-63.
[27]
Matsui Y, Takagi H, Qu X, et al. Distinct role of autophagy in the heart during ischemia and reperfusion: Roles of AMPK and Beclin 1 in mediating autophagy. Circ Res 2007; 100(6): 914-22.
[28]
Dosenko VE, Nagibin VS, Tumanovska LV, Moibenko AA. Protective effect of autophagy in anoxia-reoxygenation of isolated cardiomyocyte? Autophagy 2006; 2(4): 305-6.
[29]
Kanamori H, Takemura G, Goto K, et al. Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion. Am J Physiol Heart Circ Physiol 2011; 300(6): H2261-71.
[30]
Han Z, Cao J, Song D, et al. Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/reperfusion injury in normal mice, but not diabetic mice. PLoS One 2014; 9(1): e86838.
[31]
Wei M, Xin P, Li S, et al. Repeated remote ischemic postconditioning protects against adverse left ventricular remodeling and improves survival in a rat model of myocardial infarction. Circ Res 2011; 108(10): 1220-5.
[32]
Xu J, Sun S, Lu X, Hu X, Yang M, Tang W. Remote ischemic pre- and postconditioning improve postresuscitation myocardial and cerebral function in a rat model of cardiac arrest and resuscitation. Crit Care Med 2015; 43(1): e12-8.
[33]
Maslov LN, Oeltgen PR, Lishmanov YuB, et al. Activation of peripheral opioid receptors increases cardiac tolerance to arrhythmogenic effect of ischemia/reperfusion. Acad Emerg Med 2014; 21(1): 31-9.
[34]
Baxter GF. The neutrophil as a mediator of myocardial ischemia-reperfusion injury: time to move on. Basic Res Cardiol 2002; 97(4): 268-75.
[35]
Luster AD. Chemokines–chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338(7): 436-45.
[36]
Tang YH, Yang JS, Xiang HY, Xu JJ. PI3K-Akt/eNOS in remote postconditioning induced by brief pulmonary ischemia. Clin Invest Med 2014; 37(1): E26-37.
[37]
Wang N, Wang GS, Yu HY, Mi L, Guo LJ, Gao W. Myocardial protection of remote ischemic postconditioning during primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction. Beijing Da Xue Xue Bao 2014; 46(6): 838-43.
[38]
Zhong H, Gao Z, Chen M, et al. Cardioprotective effect of remote ischemic postconditioning on children undergoing cardiac surgery: a randomized controlled trial. Paediatr Anaesth 2013; 23(8): 726-33.
[39]
Hong DM, Jeon Y, Lee CS, et al. Effects of remote ischemic preconditioning with postconditioningin patients undergoing off-pump coronary artery bypass surgery - randomized controlled trial. Circ J 2012; 76(4): 884-90.
[40]
Hong DM, Lee EH, Kim HJ, et al. Does remote ischaemic preconditioning with postconditioning improve clinical outcomes of patients undergoing cardiac surgery? remote ischaemic preconditioning with postconditioning outcome trial. Eur Heart J 2014; 35(3): 176-83.
[41]
Carrasco-Chinchilla F, Muñoz-García AJ, Domínguez-Franco A, et al. Remote ischaemic postconditioning: does it protect against ischaemic damage in percutaneous coronary revascularisation? Randomised placebo-controlled clinical trial. Heart 2013; 99(19): 1431-7.
[42]
Crimi G, Pica S, Raineri C, et al. Remote ischemic post-conditioning of the lower limb during primary percutaneous coronary intervention safely reduces enzymatic infarct size in anterior myocardial infarction: a randomized controlled trial. JACC Cardiovasc Interv 2013; 6(10): 1055-63.
[43]
Prunier F, Angoulvant D, Saint Etienne C, et al. The RIPOST-MI study, assessing remote ischemic perconditioning alone or in combination with local ischemic postconditioning in ST-segment elevation myocardial infarction. Basic Res Cardiol 2014; 109(2): 400.
[44]
White SK, Frohlich GM, Sado DM, et al. Remote ischemic conditioning reduces myocardial infarct size and edema in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc Interv 2015; 8(1 Pt B): 178-88.
[45]
Verouhis D, Sörensson P, Gourine A, et al. Effect of remote ischemic conditioning on infarct size in patients with anterior ST-elevation myocardial infarction. Am Heart J 2016; 181: 66-73.
[46]
Cho YJ, Lee EH, Lee K, et al. Long-term clinical outcomes of Remote Ischemic Preconditioning and Postconditioning Outcome (RISPO) trial in patients undergoing cardiac surgery. Int J Cardiol 2017; 231: 84-9.
[47]
Jones WK, Fan GC, Liao S, et al. Peripheral nociception associated with surgical incision elicits remote nonischemic cardioprotection via neurogenic activation of protein kinase C signaling. Circulation 2009; 120(11)(Suppl.): S1-9.
[48]
Li YJ, Xiao ZS, Peng CF, Deng HW. Calcitonin gene-related peptide-induced preconditioning protects against ischemia-reperfusion injury in isolated rat hearts. Eur J Pharmacol 1996; 311(2-3): 163-7.
[49]
Wang Q, Cheng Y, Xue FS, et al. Postconditioning with vagal stimulation attenuates local and systemic inflammatory responses to myocardial ischemia reperfusion injury in rats. Inflamm Res 2012; 61(11): 1273-82.
[50]
Wang X, Wang J, Tu T, et al. Remote ischemic postconditioning protects against myocardial ischemia-reperfusion injury by inhibition of the RAGE-HMGB1 pathway. BioMed Res Int 2018; 2018: 4565630.
[51]
Song Y, Shan JG, Xue Z, et al. Remote postconditioning induced by trauma protects the mouse heart against ischemia reperfusion injury. Involvement of the neural pathway and molecular mechanisms. Cardiovasc Drugs Ther 2016; 30(3): 271-80.
[52]
Rasmussen MM, Reimer KA, Kloner RA, Jennings RB. Infarct size reduction by propranolol before and after coronary ligation in dogs. Circulation 1977; 56(5): 794-8.
[53]
Lishmanov YB, Maslov LN, Mukhomedzyanov AV. Role of β-Adrenoceptors and L-type Ca2+-channels in the mechanism of reperfusion-induced heart Injury. Bull Exp Biol Med 2016; 161(1): 20-3.
[54]
Serejo FC, Rodrigues LF, da Silva Tavares KC, de Carvalho AC, Nascimento JH. Cardioprotective properties of humoral factors released from rat hearts subject to ischemic preconditioning. J Cardiovasc Pharmacol 2007; 49(4): 214-20.
[55]
Breivik L, Helgeland E, Aarnes EK, Mrdalj J, Jonassen AK. Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/Akt-dependent cell-survival signaling at reperfusion. Basic Res Cardiol 2011; 106(1): 135-45.
[56]
Liang D, He XB, Wang Z, et al. Remote limb ischemic postconditioning promotes motor function recovery in a rat model of ischemic stroke via the up-regulation of endogenous tissue kallikrein. CNS Neurosci Ther 2018; 24(6): 519-27.
[57]
Chen GZ, Shan XY, Li XS, Tao HM. Remote ischemic postconditioning protects the brain from focal ischemia/reperfusion injury by inhibiting autophagy through the mTOR/p70S6K pathway. Neurol Res 2018; 40(3): 182-8.
[58]
Hu X, Lv T, Yang SF, Zhang XH, Miao YF. Limb remote ischemic postconditioning reduces injury and improves longterm behavioral recovery in rats following subarachnoid hemorrhage: Possible involvement of the autophagic process. Mol Med Rep 2018; 17(1): 21-30.
[59]
Sandweiss AJ, Azim A, Ibraheem K, et al. Remote ischemic conditioning preserves cognition and motor coordination in a mouse model of traumatic brain injury. J Trauma Acute Care Surg 2017; 83(6): 1074-81.
[60]
Gao X, Liu Y, Xie Y, Wang Y, Qi S. Remote ischemic postconditioning confers neuroprotective effects via inhibition of the BID-mediated mitochondrial apoptotic pathway. Mol Med Rep 2017; 16(1): 515-22.
[61]
Samii A, Bickel U, Stroth U, Pardridge WM. Blood-brain barrier transport of neuropeptides: Analysis with a metabolically stable dermorphin analogue. Am J Physiol 1994; 267: E124-31.
[62]
Klabunde RE. Dipyridamole inhibition of adenosine metabolism in human blood. Eur J Pharmacol 1983; 93(1-2): 21-6.
[63]
Krylatov AV, Maslov LN, Voronkov NS, et al. Reactive oxygen species as intracellular signaling molecules in the cardiovascular system. Curr Cardiol Rev 2018; 14(4): 290-300.
[64]
Yellon DM, Downey JM. Preconditioning the myocardium: From cellular physiology to clinical cardiology. Physiol Rev 2003; 83(4): 1113-51.
[65]
Bi X, Zhang G, Wang X, et al. Endoplasmic reticulum chaperone GRP78 protects heart from ischemia/reperfusion injury through Akt activation. Circ Res 2018; 122(11): 1545-54.
[66]
Hausenloy DJ, Yellon DM. Reperfusion injury salvage kinase signalling: Taking a RISK for cardioprotection. Heart Fail Rev 2007; 12(3-4): 217-34.
[67]
Gao S, Zhan L, Yang Z, et al. Remote limb ischaemic postconditioning protects against myocardial ischaemia/reperfusion injury in mice: activation of JAK/STAT3-mediated Nrf2-antioxidant signalling. Cell Physiol Biochem 2017; 43(3): 1140-51.
[68]
Malemud CJ. The role of the JAK/STAT signal pathway in rheumatoid arthritis. Ther Adv Musculoskelet Dis 2018; 10(5-6): 117-27.
[69]
Yamaoka K, Saharinen P, Pesu M, Holt VE, Silvennoinen O, O’Shea JJ. The Janus kinases (Jaks). Genome Biol 2004; 5(12): 253.
[70]
Imada K, Leonard WJ. The Jak-STAT pathway. Mol Immunol 2000; 37(1-2): 1-11.
[71]
Cohen MV, Downey JM. Is it time to translate ischemic preconditioning’s mechanism of cardioprotection into clinical practice? J Cardiovasc Pharmacol Ther 2011; 16(3-4): 273-80.
[72]
Chen CH, Budas GR, Churchill EN, Disatnik MH, Hurley TD, Mochly-Rosen D. Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science 2008; 321(5895): 1493-5.
[73]
Kleinbongard P, Skyschally A, Gent S, Pesch M, Heusch G. STAT3 as a common signal of ischemic conditioning: A lesson on “rigor and reproducibility” in preclinical studies on cardioprotection. Basic Res Cardiol 2017; 113(1): 3.
[74]
Guanizo AC, Fernando CD, Garama DJ, Gough DJ. STAT3: A multifaceted oncoprotein. Growth Factors 2018; 6: 1-14.
[75]
Wang C, Li H, Wang S, et al. Repeated non-invasive limb ischemic preconditioning confers cardioprotection through PKC-Ԑ/STAT3 signaling in diabetic rats. Cell Physiol Biochem 2018; 45(5): 2107-21.
[76]
Wang YY, Chen J, Liu XM, Zhao R, Zhe H. Nrf2-mediated metabolic reprogramming in cancer. Oxid Med Cell Longev 2018; 2018: 9304091.
[77]
Huang Y, Li W, Su ZY, Kong AN. The complexity of the Nrf2 pathway: beyond the antioxidant response. J Nutr Biochem 2015; 26(12): 1401-13.
[78]
Guo Y, Yu S, Zhang C, Kong AN. Epigenetic regulation of Keap1-Nrf2 signaling Free Radic Biol Med 2015; 88(Pt B): 337-49.
[79]
Liu XF, Zhou DD, Xie T, et al. The Nrf2 Signaling in retinal ganglion cells under oxidative stress in ocular neurodegenerative diseases. Int J Biol Sci 2018; 14(9): 1090-8.
[80]
Pennefather P, Lancaster B, Adams PR, Nicoll RA. Two distinct Ca-dependent K currents in bullfrog sympathetic ganglion cells. Proc Natl Acad Sci USA 1985; 82(9): 3040-4.
[81]
Petersen OH, Maruyama Y. Calcium-activated potassium channels and their role in secretion. Nature 1984; 307(5953): 693-6.
[82]
Trautmann A, Marty A. Activation of Ca-dependent K channels by carbamoylcholine in rat lacrimal glands. Proc Natl Acad Sci USA 1984; 81(2): 611-5.
[83]
Candia S, Garcia ML, Latorre R. Mode of action of iberiotoxin, a potent blocker of the large conductance Ca2+-activated K+ channel. Biophys J 1992; 63(2): 583-90.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 3
Year: 2019
Page: [177 - 187]
Pages: 11
DOI: 10.2174/1573403X15666190226095820
Price: $58

Article Metrics

PDF: 48
HTML: 2
PRC: 1