Peptides Are Cardioprotective Drugs of the Future: The Receptor and Signaling Mechanisms of the Cardioprotective Effect of Glucagon-like Peptide-1 Receptor Agonists

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4900 - 4900

Published: April 30, 2024

The high mortality rate among patients with acute myocardial infarction (AMI) is one of the main problems modern cardiology. It quite obvious that there an urgent need to create more effective drugs for treatment AMI than those currently used in clinic. Such could be enzyme-resistant peptide analogs glucagon-like peptide-1 (GLP-1). GLP-1 receptor (GLP1R) agonists can prevent ischemia/reperfusion (I/R) cardiac injury. In addition, chronic administration GLP1R alleviate development adverse remodeling infarction, hypertension, and diabetes mellitus. protect heart against oxidative stress reduce proinflammatory cytokine (IL-1β, TNF-α, IL-6, MCP-1) expression myocardium. stimulation inhibits apoptosis, necroptosis, pyroptosis, ferroptosis cardiomyocytes. activation augments autophagy mitophagy downregulate reactive species generation through Epac GLP1R/PI3K/Akt/survivin pathway. GLP1R, kinases (PKCε, PKA, Akt, AMPK, PI3K, ERK1/2, mTOR, GSK-3β, PKG, MEK1/2, MKK3), enzymes (HO-1 eNOS), transcription factors (STAT3, CREB, Nrf2, FoxO3), KATP channel opening, MPT pore closing are involved cardioprotective effect agonists.

Language: Английский

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K_ATP channels are regulators of programmed cell death and targets for the creation of novel drugs against ischemia/reperfusion cardiac injury

Fundamental and Clinical Pharmacology, Journal Year: 2023, Volume and Issue: 37(6), P. 1020 - 1049

Published: May 23, 2023

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

Language: Английский

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Angiotensin 1–7 increases cardiac tolerance to ischemia/reperfusion and mitigates adverse remodeling of the heart—The signaling mechanism

Fundamental and Clinical Pharmacology, Journal Year: 2024, Volume and Issue: 38(3), P. 489 - 501

Published: Feb. 4, 2024

Abstract Background The high mortality rate of patients with acute myocardial infarction (AMI) remains the most pressing issue modern cardiology. Over past 10 years, there has been no significant reduction in among AMI. It is quite obvious that an urgent need to develop fundamentally new drugs for treatment Angiotensin 1–7 some promise this regard. Objective objective article analysis published data on cardioprotective properties angiotensin 1–7. Methods PubMed, Scopus, Science Direct, and Google Scholar were used search articles study. Results increases cardiac tolerance ischemia/reperfusion mitigates adverse remodeling heart. can prevent not only ischemic but also reperfusion injury. activation Mas receptor plays a key role these effects alleviates Ca 2+ overload cardiomyocytes reactive oxygen species production (I/R) myocardium. possible both are involved 1–7‐triggered I/R. Furthermore, inhibits apoptosis stimulates autophagy cells. There indirect evidence suggesting ferroptosis cardiomyocytes. Moreover, possesses anti‐inflammatory properties, possibly achieved through NF‐kB activity inhibition. Phosphoinositide 3‐kinase, Akt, NO synthase infarct‐reducing effect However, specific end‐effector impact unknown. Conclusion molecular nature infarct‐limiting elucidated. Perhaps, sarcolemmal K ATP channel or mitochondrial channel.

Language: Английский

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Panoptosis Targets the Mechanism of PRDX1 Involvement in Acute Myocardial Infarction via ZBP1

Journal of Cellular Biochemistry, Journal Year: 2025, Volume and Issue: 126(3)

Published: March 1, 2025

PANoptosis is involved in various pathological processes, but its role acute myocardial infarction (AMI) remains unclear. This study aimed to explore the mechanism by which AMI. GSE172270 was used as an internal test set, and GSE159657 served external validation set identify disease targets for WGCNA performed potential hub genes associated with Then, related among of AMI were screened. Additionally, human cardiomyocytes AC16 mouse HL-1 cultured sugar-free serum-free medium 4 h 12 h, expression key regulating detected qRT-PCR. Finally, mRNA interference overexpression experiments conducted verify mRNAs. A total 45 upregulated 125 downregulated differentially expressed (DEGs) identified data set. 891 In 695 552 DEGs identified. Four AMI-PANoptosis (PRDX1, MMACHC, BLVRB, TXNL1) Through qRT-PCR verification, PRDX1 most specific significant gene. The positive regulator ZPB1 upregulated, while negative TAK1 downregulated. cell death (MLKL, p-MLKL, Caspase-3, Caspase-7, GSDMD) culture. However, reversed these effects. Our demonstrated that a

Language: Английский

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Role of curcumin in ischemia and reperfusion injury

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 20, 2023

Ischemia-reperfusion injury (IRI) is an inevitable pathological process after organic transplantations. Although traditional treatments restore the blood supply of ischemic organs, damage caused by IRI always ignored. Therefore, ideal and effective therapeutic strategy to mitigate warrented. Curcumin a type polyphenols, processing such properties as anti-oxidative stress, anti-inflammation anti-apoptosis. However, although many researches have been confirmed that curcumin can exert great effects on mitigation IRI, there are still some controversies about its underlying mechanisms among these researches. Thus, this review summarize protective role against well current researches, so clarify clearly provide clinicians novel idea therapy for IRI.

Language: Английский

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Mechanisms of doxorubicin-induced cardiac inflammation and fibrosis; therapeutic targets and approaches

Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 761, P. 110140 - 110140

Published: Sept. 6, 2024

Language: Английский

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Kaempferol inhibits cardiomyocyte pyroptosis via promoting O-GlcNAcylation of GSDME and improved acute myocardial infarction

BMC Pharmacology and Toxicology, Journal Year: 2025, Volume and Issue: 26(1)

Published: April 8, 2025

Language: Английский

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PANoptosis: a potential target of atherosclerotic cardiovascular disease

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

PANoptosis is a newly discovered cell death pathway triggered by the innate immunizer, which in turn promotes assembly of PANoptosome and activates downstream effectors. As special mode, it characterized apoptosis, pyroptosis, necroptosis at same time; therefore, not feasible to inhibit suppressing single pathway. However, active ingredients targeting can effectively PANoptosis.Given importance disease, would be an important therapeutic tool. Previous studies have focused more on infectious diseases cancer, role cardiovascular field has been comprehensively addressed. While ASCVD number one killer diseases, explore new targets determine future research directions. Therefore, this review focuses PANoptosome, molecular mechanism PANoptosis, related mechanisms leading such as myocardial infarction, ischemic cardiomyopathy stroke, order provide perspective for prevention treatment ASCVD.

Language: Английский

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Prognostic significance of IL‐18 in acute coronary syndrome patients

Clinical Cardiology, Journal Year: 2024, Volume and Issue: 47(2)

Published: Jan. 29, 2024

Abstract Background After acute coronary syndrome (ACS), inflammation aids healing but may harm the heart. Interleukin (IL)‐18 and IL‐1β are pivotal proinflammatory cytokines released during pyroptosis, a process that initiates sustains inflammation. This study aimed to evaluate levels of circulating IL‐18 progression ACS determine their association with subsequent clinical events in patients. Hypothesis Circulating associated Methods Employing immunoassays, we examined plasma 159 patients matched them healthy controls. The primary composite endpoint included recurrent unstable angina, myocardial infarction, heart failure exacerbation, stroke, or cardiovascular death. Results exhibited significant increase levels, measuring 6.36 [4.46−9.88] × 10 2 pg/mL, contrast control group at 4.04 [3.21−4.94] pg/mL ( p < 0.001). Conversely, remained unchanged compared group. Following 25‐month follow‐up, exceeding median an important prognostic factor for adverse (hazard ratio = 2.37, 95% confidence interval: 1.14−4.91, 0.021). Besides, displayed nonlinear 0.044). Subgroup analysis revealed correlation between risk was not significantly affected by factors such as age, sex, history diabetes, smoking, Gensini score, type (all interaction >0.05). Conclusion appears hold potential predictive marker anticipating outcomes ACS.

Language: Английский

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Do platelets protect the heart against ischemia/reperfusion injury or exacerbate cardiac ischemia/reperfusion injury? The role of PDGF, VEGF, and PAF

Life Sciences, Journal Year: 2024, Volume and Issue: 347, P. 122617 - 122617

Published: April 11, 2024

Language: Английский

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