Myocardial ischemia/reperfusion: Translational pathophysiology of ischemic heart disease

Med, Год журнала: 2024, Номер 5(1), С. 10 - 31

Опубликована: Янв. 1, 2024

Ischemic heart disease is the greatest health burden and most frequent cause of death worldwide. Myocardial ischemia/reperfusion pathophysiological substrate ischemic disease. Improvements in prevention treatment have reduced mortality developed countries over last decades, but further progress now stagnant, morbidity from developing are increasing. Significant problems remain to be resolved require a better understanding. The present review attempts briefly summarize state art myocardial research, with view on both its coronary vascular aspects, define cutting edges where mechanistic knowledge needed facilitate translation clinical practice.

Язык: Английский

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Coronary microvascular obstruction and dysfunction in patients with acute myocardial infarction

Nature Reviews Cardiology, Год журнала: 2023, Номер 21(5), С. 283 - 298

Опубликована: Ноя. 24, 2023

Язык: Английский

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Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

Redox Biology, Год журнала: 2023, Номер 67, С. 102894 - 102894

Опубликована: Окт. 6, 2023

The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury cardioprotection. In first part, continued need for cardioprotection beyond that by rapid reperfusion acute infarction is emphasized. Then, pathomechanisms to myocardium coronary circulation different modes cell death are characterized. Different mechanical pharmacological interventions protect ischemic/reperfused elective percutaneous artery bypass grafting, cardiotoxicity from cancer therapy detailed. second part keeps focus on ROS providing a comprehensive overview molecular cellular mechanisms involved injury. Starting mitochondria as main sources targets myocardium, complex network extracellular processes discussed, including relationships with Ca2+ homeostasis, thiol group redox balance, hydrogen sulfide modulation, cross-talk NAPDH oxidases, exosomes, cytokines growth factors. While mechanistic insights needed improve our current therapeutic approaches, advancements knowledge ROS-mediated indicate facets oxidative stress opposed requirement physiological protective reactions. This inevitable contrast likely underlie unsuccessful clinical trials limits development novel cardioprotective simply based upon removal.

Язык: Английский

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Reperfusion Injury in Patients With Acute Myocardial Infarction

Journal of the American College of Cardiology, Год журнала: 2024, Номер 83(22), С. 2196 - 2213

Опубликована: Май 27, 2024

Язык: Английский

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The RISK pathway leading to mitochondria and cardioprotection: how everything started

Basic Research in Cardiology, Год журнала: 2023, Номер 118(1)

Опубликована: Май 26, 2023

Abstract Ischaemic heart disease, which often manifests clinically as myocardial infarction (MI), remains a major cause of mortality worldwide. Despite the development effective pre-clinical cardioprotective therapies, clinical translation has been disappointing. Nevertheless, ‘reperfusion injury salvage kinase’ (RISK) pathway appears to be promising target for cardioprotection. This is crucial induction cardioprotection by numerous pharmacological and non-pharmacological interventions, such ischaemic conditioning. An important component effects RISK involves prevention mitochondrial permeability transition pore (MPTP) opening subsequent cardiac cell death. Here, we will review historical perspective focus on its interaction with mitochondria in setting

Язык: Английский

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Perspective: mitochondrial STAT3 in cardioprotection

Basic Research in Cardiology, Год журнала: 2023, Номер 118(1)

Опубликована: Авг. 24, 2023

Activation of signal transducer and activator transcription 3 (STAT3) has been identified as a key cardioprotective not only in animal studies but also humans-in animals, STAT3 is causally involved cardioprotection. In response to late ischemic conditioning, canonical function activation upregulates the expression anti-apoptotic proteins. its non-canonical function, activated during conditioning part cytosolic survival activating factor enhancement pathway. Activated imported localized mitochondria. Mitochondrial stimulates activity mitochondrial electron transport chain complex I, reduces reactive oxygen species production permeability transition pore opening. Finally, two novel aspects STAT cardioprotection are discussed: genetic variance encoding region potential primordial confounding variable for cardioprotection, sodium-glucose cotransporter 2 inhibitors through activation.

Язык: Английский

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Primordial non-responsiveness: a neglected obstacle to cardioprotection

European Heart Journal, Год журнала: 2023, Номер 44(19), С. 1687 - 1689

Опубликована: Март 21, 2023

Schematic diagram listing the established confounders of cardioprotection and characterizing in more detail features novel confounder 'primordial non-responsiveness to cardioprotection', as evidenced by lack protection (reduced arrhythmias, contractile dysfunction, infarct size, coronary microvascular obstruction) from ischaemic conditioning interventions rat pig strains.

Язык: Английский

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Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy

Cells, Год журнала: 2023, Номер 12(10), С. 1432 - 1432

Опубликована: Май 20, 2023

Pharmacological conditioning aims to protect the heart from myocardial ischemia-reperfusion injury (IRI). Despite extensive research in this area, today, a significant gap remains between experimental findings and clinical practice. This review provides an update on recent developments pharmacological setting summarizes evidence of these cardioprotective strategies perioperative setting. We start describing crucial cellular processes during ischemia reperfusion that drive acute IRI through changes critical compounds (∆GATP, Na+, Ca2+, pH, glycogen, succinate, glucose-6-phosphate, mitoHKII, acylcarnitines, BH4, NAD+). These all precipitate common end-effector mechanisms IRI, such as reactive oxygen species (ROS) generation, Ca2+ overload, mitochondrial permeability transition pore opening (mPTP). further discuss novel promising interventions targeting processes, with emphasis cardiomyocytes endothelium. The limited translatability basic practice is likely due lack comorbidities, comedications, peri-operative treatments preclinical animal models, employing only monotherapy/monointervention, use no-flow (always models) versus low-flow (often humans). Future should focus improved matching models reality, aligning multitarget therapy optimized dosing timing towards human condition.

Язык: Английский

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Multiscale drug screening for cardiac fibrosis identifies MD2 as a therapeutic target

Cell, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

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Empagliflozin prevents heart failure through inhibition of the NHE1-NO pathway, independent of SGLT2

Basic Research in Cardiology, Год журнала: 2024, Номер 119(5), С. 751 - 772

Опубликована: Июль 24, 2024

Sodium glucose cotransporter 2 inhibitors (SGLT2i) constitute the only medication class that consistently prevents or attenuates human heart failure (HF) independent of ejection fraction. We have suggested earlier protective mechanisms SGLT2i Empagliflozin (EMPA) are mediated through reductions in sodium hydrogen exchanger 1 (NHE1)-nitric oxide (NO) pathway, SGLT2. Here, we examined role SGLT2, NHE1 and NO a murine TAC/DOCA model HF. SGLT2 knockout mice showed attenuated systolic dysfunction without having an effect on other signs EMPA protected against diastolic dysfunction, hypertrophy, fibrosis, increased Nppa/Nppb mRNA expression lung/liver edema. In addition, prevented increases oxidative stress, calcium calcium/calmodulin-dependent protein kinase II activation to equal degree WT KO animals. particular, while activity was isolated cardiomyocytes from untreated HF, treatment this. Since is not required for effects EMPA, pathway between further explored vivo with specific NHE1-inhibitor Cariporide mimicked protection by additional EMPA. On hand, inhibition NOS L-NAME deteriorated HF conclusion, data support beneficial NHE1-NO TAC/DOCA-induced inhibition.

Язык: Английский

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