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Background: Catecholamines and β‐adrenergic receptors (β‐ARs) play an important role in the regulation of cardiac tolerance to the impact of ischemia and reperfusion. This systematic review analyzed the molecular mechanisms of the cardioprotective activity of β‐AR ligands. Methods: We performed an electronic search of topical articles using PubMed databases from 1966 to 2023. We cited original in vitro and in vivo studies and review articles that documented the cardioprotective properties of β‐AR agonists and antagonists. Results: The infarct‐reducing effect of β‐AR antagonists did not depend on a decrease in the heart rate. The target for β‐blockers is not only cardiomyocytes but also neutrophils. β1‐blockers (metoprolol, propranolol, timolol) and the selective β2‐AR agonist arformoterol have an infarct‐reducing effect in coronary artery occlusion (CAO) in animals. Antagonists of β1‐ and β2‐АR (metoprolol, propranolol, nadolol, carvedilol, bisoprolol, esmolol) are able to prevent reperfusion cardiac injury. All β‐AR ligands that reduced infarct size are the selective or nonselective β1‐blockers. It was hypothesized that β1‐AR blocking promotes an increase in cardiac tolerance to I/R. The activation of β1‐AR, β2‐AR, and β3‐AR can increase cardiac tolerance to I/R. The cardioprotective effect of β‐AR agonists is mediated via the activation of kinases and reactive oxygen species production. Conclusions: It is unclear why β‐blockers with the similar receptor selectivity have the infarct‐sparing effect while other β‐blockers with the same selectivity do not affect infarct size. What is the molecular mechanism of the infarct‐reducing effect of β‐blockers in reperfusion? Why did in early studies β‐blockers decrease the mortality rate in patients with acute myocardial infarction (AMI) and without reperfusion and in more recent studies β‐blockers had no effect on the mortality rate in patients with AMI and reperfusion? The creation of more effective β‐AR ligands depends on the answers to these questions. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Currently, there is no effective therapy for takotsubo syndrome (stress‐induced cardiac injury in humans) in the clinics. It has previously been shown that β2‐adrenergic receptor (β2‐AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome.The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress‐induced cardiomyopathy.Stress‐induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours.The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase‐MB, syndecan‐1, and thrombomodulin after 24 hours of stress. Administration of β2‐AR agonist formoterol (50 μg/kg) four times during 24‐hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL‐positive cardiomyocytes, serum creatine kinase‐MB, syndecan‐1, and thrombomodulin levels.Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress‐induced cardiac injury can be mitigated by activation of the β2‐AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress. [ABSTRACT FROM AUTHOR]

The thymus represents a primary organ of the immune system, harboring the generation and maturation of T lymphocytes. Starting from childhood, the thymus undergoes involution, being replaced with adipose tissue, and by an advanced age nearly all the thymus parenchyma is represented by adipocytes. This decline of thymic function is associated with compromised maturation and selection of T lymphocytes, which may directly impact the development of inflammation and induce various autoinflammatory disorders, including atherosclerosis. For a long time, thymus health in adults has been ignored. The process of adipogenesis in thymus and impact of thymic fat on cardiometabolism remains a mysterious process, with many issues being still unresolved. Meanwhile, thymus functional activity has a potential to be regulated, since islets of thymopoeisis remain in adults even at an advanced age. The present review describes the intricate process of thymic adipose involution, focusing on the issues of the thymus' role in the development of atherosclerosis and metabolic health, tightly interconnected with the state of vessels. We also review the recent information on the key molecular pathways and biologically active substances that may be targeted to manipulate both thymic function and atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: The high mortality rate of patients with acute myocardial infarction (AMI) remains the most pressing issue of modern cardiology. Over the past 10 years, there has been no significant reduction in mortality among patients with AMI. It is quite obvious that there is an urgent need to develop fundamentally new drugs for the treatment of AMI. Angiotensin 1–7 has some promise in this regard. Objective: The objective of this article is analysis of published data on the cardioprotective properties of angiotensin 1–7. Methods: PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study. Results: Angiotensin 1–7 increases cardiac tolerance to ischemia/reperfusion and mitigates adverse remodeling of the heart. Angiotensin 1–7 can prevent not only ischemic but also reperfusion cardiac injury. The activation of the Mas receptor plays a key role in these effects of angiotensin 1–7. Angiotensin 1–7 alleviates Ca2+ overload of cardiomyocytes and reactive oxygen species production in ischemia/reperfusion (I/R) of the myocardium. It is possible that both effects are involved in angiotensin 1–7‐triggered cardiac tolerance to I/R. Furthermore, angiotensin 1–7 inhibits apoptosis of cardiomyocytes and stimulates autophagy of cells. There is also indirect evidence suggesting that angiotensin 1–7 inhibits ferroptosis in cardiomyocytes. Moreover, angiotensin 1–7 possesses anti‐inflammatory properties, possibly achieved through NF‐kB activity inhibition. Phosphoinositide 3‐kinase, Akt, and NO synthase are involved in the infarct‐reducing effect of angiotensin 1–7. However, the specific end‐effector of the cardioprotective impact of angiotensin 1–7 remains unknown. Conclusion: The molecular nature of the end‐effector of the infarct‐limiting effect of angiotensin 1–7 has not been elucidated. Perhaps, this end‐effector is the sarcolemmal KATP channel or the mitochondrial KATP channel. [ABSTRACT FROM AUTHOR]

Background: The use of percutaneous coronary intervention (PCI) in patients with ST‐segment elevation myocardial infarction (STEMI) is associated with a mortality rate of 5%–7%. It is clear that there is an urgent need to develop new drugs that can effectively prevent cardiac reperfusion injury. ATP‐sensitive K+ (KATP) channel openers (KCOs) can be classified as such drugs. Results: KCOs prevent irreversible ischemia and reperfusion injury of the heart. KATP channel opening promotes inhibition of apoptosis, necroptosis, pyroptosis, and stimulation of autophagy. KCOs prevent the development of cardiac adverse remodeling and improve cardiac contractility in reperfusion. KCOs exhibit antiarrhythmic properties and prevent the appearance of the no‐reflow phenomenon in animals with coronary artery occlusion and reperfusion. Diabetes mellitus and a cholesterol‐enriched diet abolish the cardioprotective effect of KCOs. Nicorandil, a KCO, attenuates major adverse cardiovascular event and the no‐reflow phenomenon, reduces infarct size, and decreases the incidence of ventricular arrhythmias in patients with acute myocardial infarction. Conclusion: The cardioprotective effect of KCOs is mediated by the opening of mitochondrial KATP (mitoKATP) and sarcolemmal KATP (sarcKATP) channels, triggered free radicals' production, and kinase activation. [ABSTRACT FROM AUTHOR]

The acute myocardial infarction (AMI) and sudden cardiac death (SCD), both associated with acute cardiac ischemia, are one of the leading causes of adult death in economically developed countries. The development of new approaches for the treatment and prevention of AMI and SCD remains the highest priority for medicine. A study on the cardiovascular effects of chronic hypoxia (CH) may contribute to the development of these methods. Chronic hypoxia exerts both positive and adverse effects. The positive effects are the infarct-reducing, vasoprotective, and antiarrhythmic effects, which can lead to the improvement of cardiac contractility in reperfusion. The adverse effects are pulmonary hypertension and right ventricular hypertrophy. This review presents a comprehensive overview of how CH enhances cardiac tolerance to ischemia/reperfusion. It is an indepth analysis of the published data on the underlying mechanisms, which can lead to future development of the cardioprotective effect of CH. A better understanding of the CH-activated protective signaling pathways may contribute to new therapeutic approaches in an increase of cardiac tolerance to ischemia/reperfusion. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) remains the leading cause of mortality in the world, highlighting an urgent need for the development of novel, more effective approaches for the treatment of AMI. Remote postconditioning (RPost) of the heart could be a useful approach. It was demonstrated that RPost triggers infarct size reduction, improves contractile function of the heart in reperfusion, mitigates apoptosis, and stimulates autophagy in animals with coronary artery occlusion and reperfusion. Endogenous opioid peptides and adenosine could be involved in RPost. It was found that kinases and NO-synthase participate in RPost. KATP channels, MPT pore, and STAT3 could be hypothetical end-effectors of RPost. Metabolic syndrome and old age abolish the cardioprotective effect of RPost in rats. The data on the efficacy of RPost in clinical practice are inconsistent. These data are discussed in the review. [ABSTRACT FROM AUTHOR]

The purpose of this review is to analyze the involvement of protein kinases in the cardioprotective mechanism induced by chronic hypoxia. It has been reported that chronic intermittent hypoxia contributes to increased expression of the following kinases in the myocardium: PKCδ, PKCα, p-PKCε, p-PKCα, AMPK, p-AMPK, CaMKII, p-ERK1/2, p-Akt, PI3-kinase, p-p38, HK-1, and HK-2; whereas, chronic normobaric hypoxia promotes increased expression of the following kinases in the myocardium: PKCε, PKCβII, PKCη, CaMKII, p-ERK1/2, p-Akt, p-p38, HK-1, and HK-2. However, CNH does not promote enhanced expression of the AMPK and JNK kinases. Adaptation to hypoxia enhances HK-2 association with mitochondria and causes translocation of PKCδ, PKCβII, and PKCη to the mitochondria. It has been shown that PKCδ, PKCε, ERK1/2, and MEK1/2 are involved in the cardioprotective effect of chronic hypoxia. The role of other kinases in the cardioprotective effect of adaptation to hypoxia requires further research. [ABSTRACT FROM AUTHOR]

Cannabinoids can mimic the infarct-reducing effect of early ischemic preconditioning, delayed ischemic preconditioning, and ischemic postconditioning against myocardial ischemia/reperfusion. They do this primarily through both CB1 and CB2 receptors. Cannabinoids are also involved in remote preconditioning of the heart. The cannabinoid receptor ligands also exhibit an antiapoptotic effect during ischemia/reperfusion of the heart. The acute cardioprotective effect of cannabinoids is mediated by activation of protein kinase C, extracellular signal-regulated kinase, and p38 kinase. The delayed cardioprotective effect of cannabinoid anandamide is mediated via stimulation of phosphatidylinositol-3-kinase-Akt signaling pathway and enhancement of heat shock protein 72 expression. The delayed cardioprotective effect of another cannabinoid, Δ9-tetrahydrocannabinol, is associated with augmentation of nitric oxide (NO) synthase expression, but data on the involvement of NO synthase in the acute cardioprotective effect of cannabinoids are contradictory. The adenosine triphosphate-sensitive K(+)channel is involved in the synthetic cannabinoid HU-210-induced cardiac resistance to ischemia/reperfusion injury. Cannabinoids inhibit Na(+)/Ca(2+)exchange via peripheral cannabinoid receptor (CB2) activation that may also be related to the antiapoptotic and cardioprotective effects of cannabinoids. The cannabinoid receptor agonists should be considered as prospective group of compounds for creation of drugs that are able to protect the heart against ischemia-reperfusion injury in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: The use of percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is associated with a mortality rate of 5%-7%. It is clear that there is an urgent need to develop new drugs that can effectively prevent cardiac reperfusion injury. ATP-sensitive K + (K ATP ) channel openers (KCOs) can be classified as such drugs., Results: KCOs prevent irreversible ischemia and reperfusion injury of the heart. K ATP channel opening promotes inhibition of apoptosis, necroptosis, pyroptosis, and stimulation of autophagy. KCOs prevent the development of cardiac adverse remodeling and improve cardiac contractility in reperfusion. KCOs exhibit antiarrhythmic properties and prevent the appearance of the no-reflow phenomenon in animals with coronary artery occlusion and reperfusion. Diabetes mellitus and a cholesterol-enriched diet abolish the cardioprotective effect of KCOs. Nicorandil, a KCO, attenuates major adverse cardiovascular event and the no-reflow phenomenon, reduces infarct size, and decreases the incidence of ventricular arrhythmias in patients with acute myocardial infarction., Conclusion: The cardioprotective effect of KCOs is mediated by the opening of mitochondrial K ATP (mitoK ATP ) and sarcolemmal K ATP (sarcK ATP ) channels, triggered free radicals' production, and kinase activation., (© 2023 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Metabolic syndrome is accompanied by oxidative stress in animals and humans. The main source of ROS in experimental metabolic syndrome is NADPH oxidase and possibly adipocyte mitochondria. It is now documented that oxidative stress induces insulin resistance of adipocytes and increases secretion of leptin, MCP-1, IL-6, and TNF-α by adipocytes. It was established that oxidative stress induces a decrease in adiponectin production by adipocytes. It has also been shown that obesity itself can induce oxidative stress. Oxidative stress can cause an alteration of intracellular signaling in adipocytes that apparently leads to the formation of insulin resistance of adipocytes. Chronic stress, glucocorticoids, mineralocorticoids, angiotensin-II, TNF-α also play an important role in the pathogenesis of oxidative stress of adipocytes. Oxidative stress is not only a consequence of metabolic syndrome, but also a reason and a foundational link in the pathogenesis of the metabolic syndrome.

It was established that adaptation to chronic continuous normobaric hypoxia (CCNH) increases cardiac tolerance to ischemia and reperfusion. It was performed coronary artery occlusion (20 min) and reperfusion (3 h) in Wistar rats. CCNH promoted a decrease in the infarct size/area at risk ratio in 2-fold. CCNH promoted an increase in the nitrite/nitrate levels in blood serum and myocardium. Pretreatment with protein kinase C (PKC) inhibitor chelerythrine, NO-synthase (NOS) inhibitor L-NAME, iNOS inhibitor S-methylisothiourea, KATP channel blocker glibenclamide, mitoKATP channel blocker 5-hydroxydecanoic acid abolished the infarct-reducing effect of CCNH. The non-selective tyrosine kinase inhibitor genistein attenuated but not eliminated infarct-sparing effect of CCNH. The nNOS inhibitor 7-nitroindazole, sarcKATP channel blocker HMR 1098, MPT pore inhibitor atractyloside, PI3 kinase inhibitor wortmannin did not reverse infarct-limiting effect of CCNH. It was concluded that infarct-reducing effect of CCNH is mediated via PKC, iNOS activation and mitoKATP channel opening. While nNOS, PI3 kinase, sarcKATP channel, MPT pore are not involved in the development of CCNH-induced cardiac tolerance to impact of ischemia-reperfusion.