Endothelial Dysfunction and Diabetic Cardiomyopathy

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: April 7, 2022

The cardiovascular complications contribute to a majority of diabetes associated morbidity and mortality, accounting for 44% death in those patients with type 1 mellitus (DM) 52% deaths 2 DM. Diabetes elicits dysfunction through major mechanisms: ischemic non-ischemic. Non-ischemic injury is usually under-recognized although common DM patients, also pathogenic factor heart failure diabetic individuals complicated disease. Diabetic cardiomyopathy (DCM) defined as disease which the myocardium structurally functionally abnormal absence coronary artery disease, hypertensive, valvular, or congenital disorders theoretically caused by non-ischemic solely. Current therapeutic strategies targeting DCM mainly address increased blood glucose levels, however, effects on function are disappointed. Accumulating data indicate endothelial plays critical role initiation development DCM. Hyperglycemia, hyperinsulinemia, insulin resistance cause damages function, including barrier dysfunction, impaired nitric oxide (NO) activity, excessive reactive oxygen species (ROS) production, oxidative stress, inflammatory dysregulation. In turn, promotes myocardial metabolism, intracellular Ca 2+ mishandling, endoplasmic reticulum (ER) mitochondrial defect, accumulation advanced glycation end products, extracellular matrix (ECM) deposit, leads cardiac stiffness, fibrosis, remodeling, eventually results diastolic systolic failure. While closely related seen DCM, clinical restoring still missing. This review summarizes timely findings disorder well provides mechanical insights pathogenesis pathophysiology developing, highlights potential targets.

Language: Английский

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STAT3 signaling promotes cardiac injury by upregulating NCOA4-mediated ferritinophagy and ferroptosis in high-fat-diet fed mice

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 201, P. 111 - 125

Published: March 20, 2023

High-fat diet (HFD) intake provokes obesity and cardiac anomalies. Recent studies have found that ferroptosis plays a role in HFD-induced injury, but the underlying mechanism is largely unclear. Ferritinophagy an important part of regulated by nuclear receptor coactivator 4 (NCOA4). However, relationship between ferritinophagy damage has not been explored. In this study, we oleic acid/palmitic acid (OA/PA) increased level ferroptotic events including iron ROS accumulation, upregulation PTGS2 mRNA protein levels, reduced SOD GSH significant mitochondrial H9C2 cells, which could be reversed inhibitor ferrostatin-1 (Fer-1). Intriguingly, autophagy 3-methyladenine mitigated OA/PA-induced ferritin downregulation, overload ferroptosis. OA/PA NCOA4. Knockdown NCOA4 SiRNA partly reduction ferritin, lipid peroxidation, subsequently alleviated cell death, indicating NCOA4-mediated was required for Furthermore, demonstrated IL-6/STAT3 signaling. Inhibition or knockdown STAT3 effectively levels to protect cells from ferritinophagy-mediated ferroptosis, whereas overexpression plasmid appeared increase expression contribute classical events. Consistently, phosphorylated upregulation, activation, induction also occurred HFD-fed mice were responsible injury. addition, evidence piperlongumine, natural compound, cardiomyocytes both vitro vivo. Based on these findings, concluded one critical mechanisms contributing The STAT3/NCOA4/FTH1 axis might novel therapeutic target treatment

Language: Английский

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Fir(e)ing the Rhythm

JACC Basic to Translational Science, Journal Year: 2023, Volume and Issue: 8(6), P. 728 - 750

Published: Feb. 15, 2023

Inflammatory activation is increasingly recognized as a nonconventional risk factor for arrhythmias, and experimental studies provided robust evidence that this association mediated by direct arrhythmogenic effects of proinflammatory cytokines on cardiac cells. Additionally, inflammatory can favor arrhythmias indirectly through multiple systemic effects. Accumulating data confirm the clinical relevance these mechanisms; largest being available atrial fibrillation, acquired long-QT syndrome, ventricular arrhythmias. However, management largely neglects cytokines. This review integrates basic science research to present an updated overview topic provides future directions patient's management.

Language: Английский

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Rapidly Inhibiting the Inflammatory Cytokine Storms and Restoring Cellular Homeostasis to Alleviate Sepsis by Blocking Pyroptosis and Mitochondrial Apoptosis Pathways

Advanced Science, Journal Year: 2023, Volume and Issue: 10(14)

Published: March 17, 2023

Pyroptosis, systemic inflammation, and mitochondrial apoptosis are the three primary contributors to sepsis's multiple organ failure, ultimate cause of high clinical mortality. Currently, drugs under development only target a single pathogenesis, which is obviously insufficient. In this study, an acid-responsive hollow mesoporous polydopamine (HMPDA) nanocarrier that highly capable carrying both hydrophilic drug NAD

Language: Английский

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Mitochondria-associated endoplasmic reticulum membranes as a therapeutic target for cardiovascular diseases

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 17, 2024

Cardiovascular diseases (CVDs) are currently the leading cause of death worldwide. In 2022, CVDs contributed to 19.8 million deaths globally, accounting for one-third all global deaths. With an aging population and changing lifestyles, pose a major threat human health. Mitochondria-associated endoplasmic reticulum membranes (MAMs) communication platforms between cellular organelles regulate physiological functions, including apoptosis, autophagy, programmed necrosis. Further research has shown that MAMs play critical role in pathogenesis CVDs, myocardial ischemia reperfusion injury, heart failure, pulmonary hypertension, coronary atherosclerosis. This suggests could be important therapeutic target managing CVDs. The goal this study is summarize protein complex MAMs, discuss its pathological mechanisms terms functions such as Ca

Language: Английский

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Dapagliflozin protects heart function against type-4 cardiorenal syndrome through activation of PKM2/PP1/FUNDC1-dependent mitophagy

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 250, P. 126116 - 126116

Published: Aug. 2, 2023

Language: Английский

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So close, yet so far away: the relationship between MAM and cardiac disease

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 5, 2024

Mitochondria-associated membrane (MAM) serve as crucial contact sites between mitochondria and the endoplasmic reticulum (ER). Recent research has highlighted significance of MAM, which a platform for various protein molecules, in processes such calcium signaling, ATP production, mitochondrial structure function, autophagy. Cardiac diseases caused by any reason can lead to changes myocardial significantly impacting human health. Notably, MAM exhibits regulatory effects maintain cellular balance several cardiac conditions, obesity, diabetes mellitus, cardiotoxicity. proteins independently or interact with their counterparts, forming essential tethers ER cardiomyocytes. This review provides an overview key regulators, detailing functions. Additionally, it explores connection injuries, suggesting that precise genetic, pharmacological, physical regulation may be promising strategy preventing treating heart failure.

Language: Английский

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TLR4 Inhibition Attenuated LPS‐Induced Proinflammatory Signaling and Cytokine Release in Mouse Hearts and Cardiomyocytes

Immunity Inflammation and Disease, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 1, 2025

ABSTRACT Background Sepsis is associated with myocardial injury and early mortality. The innate immune receptor Toll‐like 4 (TLR4) can recognize pathogen‐associated‐molecular‐patterns (PAMPs) damage‐associated molecular patterns (DAMPs); the latter are released during tissue injury. We hypothesized that TLR4 inhibition reduces proinflammatory signaling cytokine release in: (1) LPS or Escherichia coli ‐treated isolated mouse heart; (2) LPS‐treated primary adult cardiomyocytes; (3) heart ischemia–reperfusion. Methods Isolated C57BL/6N male hearts were perfused for 120 min, either LPS, E. , without CLI‐095 (TLR4 inhibitor). Primary cardiomyocytes treated + CLI‐095. hearts, exposed to 35 min of global ischemia, vehicle reperfusion. Infarct size was quantified by triphenyltetrazolium staining. Cytokine expression analyzed ELISA, western blot analysis, qPCR. Results In increased cytokines (IL‐6 CXCL2), which not attenuated inhibition. reduced ( p = 0.004) IL‐6 < 0.0001) in LPS‐exposed hearts. activated nuclear‐factor κ‐light‐chain‐enhancer B cells pathway (NF‐κB) cardiomyocytes. Moreover, LPS‐induced mRNA reperfusion after ischemia (induced DAMPs release) showed infarct (39 ± 17% 26 8%, 0.034) decreased 0.006). Conclusion Inhibition ischemia–reperfused murine

Language: Английский

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Immunization induces inflammation in the mouse heart during spaceflight

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

Published: March 10, 2025

Abstract Space travel is a growing area of interest and includes initiatives such as NASA’s Moon-to-Mars Mission. Reports on the cardiovascular effects space reveal changes in morphology, metabolism, function system. In this study, response to immunization was studied mice which were housed immunized while International Station (ISS). Mice with tetanus toxoid combined adjuvant CpG (TT + CpG) vaccination using transcriptomics. Analysis mouse heart transcriptome performed flight control flight-immunized mice. The results show that aboard ISS stimulates heightened inflammation via induction nuclear factor kappa B (NF-κB) signaling pathway promote release pro-inflammatory cytokines IFNγ, IL-17 IL-6. Additional transcriptomic included alterations cytoskeleton expression transcripts associated protection from oxidative stress. summary, can occur following space. This investigation explores impact immune challenges lays groundwork for future research into additional cardiac during spaceflight.

Language: Английский

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Resveratrol: a potential alternative therapeutic agent for patients suffering from chronic obstructive pulmonary disease (COPD)

Journal of Asian Natural Products Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: March 10, 2025

This review explores the therapeutic potential of resveratrol, focusing on its molecular and cellular effects Chronic Obstructive Pulmonary Disease (COPD), bioavailability enhancement strategies, development challenges for applications in food, pharmaceuticals, postharvest sectors. Resveratrol protects lungs by activating SIRT1, reducing oxidative stress via ROS regulation through Nrf2-mediated antioxidant enzymes. It shows promise as an alternative to corticosteroids COPD cancer treatment. Encapsulation innovations resveratrol offer opportunities food fortification, minimizing risks chemical degradation isomerization during storage, paving way broader utility health nutrition applications.

Language: Английский

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