A brief overview of cardioprotective signaling

Aleksandar Jovanović

doi:10.5937/arhfarm74-52570

Aleksandar Jovanović University of Nicosia Medical School, Department of Basic and Clinical Sciences, Center for Neuroscience and Integrative Brain Research (CENIBRE)

DOI: https://doi.org/10.5937/arhfarm74-52570

Ključne reči: kardioprotekcija, srce, ishemija, reperfuzija, kondicioniranje

Sažetak

Kardioprotekcija se definiše kao intrinzična sposobnost srčanog tkiva da podnese izazove poput ishemijsko-reperfuzionih povreda i različitih metaboličkih stresova. Prvobitno je primećena kroz ishemijsko prekondicioniranje, ali je obim kardioprotekcije proširen tako da obuhvata i druge induktore kardioprotektivnih signala kao što su hipoksija, fluktuacije temperature i brojni farmakološki agensi, što sugeriše postojanje zajedničkih signalnih puteva i zaštitnih kaskada. Unutarćelijski faktori signalizacije koji doprinose kardioprotekciji za sada uključuju protein kinaze, putanju spašavanja reperfuzionih povreda (RISK), putanju SAFE (Survivor Activating Factor Enhancement), hipoksijom indukovan faktor-1α (HIF1α), mikroRNK, koneksin 43 i druge. Ovi faktori igraju uloge u aktivaciji signalnih elemenata i zaštitnih gena nizvodno, poboljšanju funkcije mitohondrija i regulisanju ekspresije proteina i citosolne funkcije kako bi omogućili kardioprotekciju. SUR2A, regulatorna podjedinica sarkolemalnih ATP-osetljivih K+ (K_ATP) kanala, autofagija i mitohondrije istaknuti su kao ključni krajnji efektori, sa mehanizmima poput regulacije mitohondrijalnih propusnih pora i aktivacije K_ATP kanala koji su ključni za kardioprotekciju. Uprkos napretku u razumevanju ovih puteva, brojni aspekti kardioprotekcije tek treba da budu bolje shvaćeni. Poseban izazov predstavlja dalje istraživanje terapijskih potencijala i, na kraju, razvoj klinički održivih strategija za zaštitu srca.

Reference

Murry CE, Jennings RB, Reimer KA. Precoditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74:1124-1136.

Jovanović A. Cardioprotective signalling: Past, present and future. Eur J Pharmacol. 2018;833:314-319.

Paulino ET. Development of Cardioprotective class based on pathophysiology of myocardial infarction: a comprehensive review. Curr Probl Cardiol. 2024;49:102480.

de Miranda DC, de Oliveira Faria, G, Hermidorff MM, Dos Santos Silva FC, de Assis LVM, Isoldi MC. Pre- and Post-Conditioning of the heart: An overview of cardioprotective signaling pathways. Curr Vasc Pharmacol. 2021;19:499-524.

Mohammed Abdul KS, Jovanović S, Du Q, Sukhodub A, Jovanović A. Upregulation of cardioprotective SUR2A by sub-hypoxic drop in oxygen. Biochim Biophys Acta -Mol Cell Res. 2014;1843:2424-2431.

Mohammed Abdul KS, Jovanović S, Du Q, Sukhodub A, Jovanović A. Mild hypoxia in vivo regulates cardioprotective SUR2A: A role for Akt and LDH. Biochim Biophys Acta-Mol Basis Dis. 2015;1852:709-719.

Mohammed Abdul KS, Jovanović S, Du Q, Sukhodub A, Jovanović A. A link between ATP and SUR2A: A novel mechanism explaining cardioprotection at high altitude. Int J Cardiol. 2015;189:73-76.

Mohammed Abdul KS, Jovanović S, Jovanović A. Exposure to 15% oxygen in vivo up-regulates cardioprotective SUR2A without affecting ERK1/2 and Akt: A crucial role for AMPK. J Cell Mol Med. 2017;21:1342-1350.

Zhang H, Hu H, Zhai C, Jing L, Tian H. Cardioprotective Strategies After Ischemia-Reperfusion Injury. Am J Cardiovasc Drugs. 2024;24:5-18.

Ramani S, Park S. HSP27 role in cardioprotection by modulating chemotherapeutic doxorubicin-induced cell death. J Mol Med (Berl). 2021;99: 771-784.

Sukhodub A, Du Q, Jovanović S, Jovanović A. Nicotinamide-rich diet protects the heart against ischaemia-reperfusion in mice: a crucial role for cardiac SUR2A. Pharmacol Res. 2010;61:564-570.

Abdul KSM, Faiz N, Jovanović A, Tan W. Isosteviol protects H9c2 cells against hypoxia-reoxygenation by activating ERK1/2. Cardiovasc Hematol Disord Drug Targets. 2021;21:73-77.

Kumar K, Singh N, Yadav HN, Maslov L, Jaggi AS. Endless journey of adenosine signaling in cardioprotective mechanism of conditioning techniques: clinical evidence. Curr Cardiol Rev. 2023;19:56-71.

Gil-Cabrerizo P, Scacchetti I, Garbayo E, Blanco-Prieto MJ. Cardiac tissue engineering for myocardial infarction treatment. Eur J Pharm Sci. 2023;185:106439.

Olas B. The cardioprotective role of nitrate-rich vegetables. Foods. 2024;13:691.

Chen L, Shi D, Guo M. The roles of PKC-δ and PKC-ε in myocardial ischemia/reperfusion injury. Pharmacol Res. 2021;170:105716.

Sukhodub A, Jovanović S, Du Q, Budas G, Clelland AK, Shen M, et al. AMP-activated protein kinase mediates preconditioning in cardiomyocytes by regulating activity and trafficking of sarcolemmal ATP-sensitive K(+) channels. J Cell Physiol. 2007;210:224-236.

Liu Y, Chen J, Fontes SK, Bautista EN, Cheng Z. Physiological and pathological roles of protein kinase A in the heart. Cardiovasc Res. 2022;118:386-398.

Park M, Sandner P, Krieg T. cGMP at the centre of attention: emerging strategies for activating the cardioprotective PKG pathway. Basic Res Cardiol. 2018;113:24.

Gallo S, Vitacolonna A, Bonzano A, Comoglio P, Crepaldi T. ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy. Int J Mol Sci. 2019;20:2164.

Efentakis P, Andreadou I, Iliodromitis KE, Triposkiadis F, Ferdinandy P, Schulz R, Iliodromitis EK. Myocardial protection and current cancer therapy: Two opposite targets with inevitable cost. Int J Mol Sci. 2022;23:14121.

Yellon DM, Beikoghli Kalkhoran S, Davidson SM. The RISK pathway leading to mitochondria and cardioprotection: how everything started. Basic Res Cardiol. 2023;118:22.

Skyschally A, Kleinbongard P, Lieder H, Gedik N, Stoian L, Amanakis G, et al. Humoral transfer and intramyocardial signal transduction of protection by remote ischemic perconditioning in pigs, rats, and mice. Am J Physiol Heart Circ Physiol. 2018;315:H159-H172.

Vainio L, Taponen S, Kinnunen SM, Halmetoja E, Szabo Z, Alakoski T, et al. GSK3β Serine 389 Phosphorylation Modulates Cardiomyocyte Hypertrophy and Ischemic Injury. Int J Mol Sci. 2021;22:13586.

Hadebe N, Cour M, Lecour S. The SAFE pathway for cardioprotection: is this a promising target? Basic Res Cardiol. 2018;113:9.

Kleinbongard P. Perspective: mitochondrial STAT3 in cardioprotection. Basic Res Cardiol. 2023;118:32.

Zheng J, Chen P, Zhong J, Cheng Y, Chen H, He Y, Chen C. HIF 1α in myocardial ischemia reperfusion injury (Review). Mol Med Rep. 2021;23:352.

Giacca M. Fulfilling the promise of RNA therapies for cardiac repair and regeneration. Stem Cells Transl Med. 2023;12:527-535.

Rusiecka OM, Montgomery J, Morel S, Batista-Almeida D, Van Campenhout R, Vinken M, et al. Canonical and non-canonical roles of connexin43 in cardioprotection. Biomolecules. 2020;10:1225.

Ding J, Yang Z, Ma H, Zhang H. Mitochondrial aldehyde dehydrogenase in myocardial ischemic and ischemia-reperfusion injury. Adv Exp Med Biol. 2019;1193:107-120.

Yadav M, Kumari P, Yadav V, Kumar S. Pharmacological preconditioning with phosphodiestrase inhibitor: an answer to stem cell survival against ischemic injury through JAK/STAT signaling. Heart Fail Rev. 2020;25:355-366.

Packer M. Cardioprotective effects of sirtuin-1 and its downstream effectors: Potential role in mediating the heart failure benefits of SGLT2 (Sodium-Glucose Cotransporter 2) inhibitors. Circ Heart Fail. 2020;13:e007197.

Lotz C, Herrmann J, Notz Q, Meybohm P, Kehl F. Mitochondria and Pharmacologic Cardiac Conditioning-At the Heart of Ischemic Injury. Int J Mol Sci. 2021;22:3224.

Singh H. Mitochondrial ion channels in cardiac function. Am J Physiol Cell Physiol. 2021;321:C812-C825.

Jovanović A. SUR2A: How to exploit this protein to treat ischaemic heart disease? Arh Farm. 2020;70:1-9.

Mahdi H, Jovanović A. SUR2A as a base for cardioprotective therapeutic strategies. Mol Biol Rep. 2022;49:6717-6723.

Chen S, Zou Y, Song C, Cao K, Cai K, Wu Y, et al. The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches. Basic Res Cardiol. 2023;118:48.

Totzeck M, Hendgen-Cotta UB, Rassaf T. Nitrite-Nitric Oxide Signaling and Cardioprotection. Adv Exp Med Biol. 2017;982:335-346.

Tappia PS, Shah AK, Ramjiawan B, Dhalla NS. Modification of ischemia/reperfusion-induced alterations in subcellular organelles by ischemic preconditioning. Int J Mol Sci. 2022;23:3425.

Kuznetsov AV, Javadov S, Margreiter R, Grimm M, Hagenbuchner J, Ausserlechner MJ. The role of mitochondria in the mechanisms of cardiac ischemia-reperfusion injury. Antioxidants (Basel). 2019;8:454.

Ding X, Zhu C, Wang W, Li M, Ma C, Gao B. SIRT1 is a regulator of autophagy: Implications for the progression and treatment of myocardial ischemia-reperfusion. Pharmacol Res. 2024;199:106957.

Penna C, Comità S, Tullio F, Alloatti G, Pagliaro P. Challenges facing the clinical translation of cardioprotection: 35 years after the discovery of ischemic preconditioning. Vascul Pharmacol. 2022;144:106995.

Kratak pregled kardioprotektivnivnih signala

Sažetak

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