Melatonin Ameliorates Atherosclerotic Plaque Vulnerability by Regulating PPARδ‐Associated Smooth Muscle Cell Phenotypic Switching

Journal of Pineal Research, Год журнала: 2024, Номер 76(5)

Опубликована: Июль 9, 2024

ABSTRACT Vulnerable atherosclerotic plaque rupture, the leading cause of fatal atherothrombotic events, is associated with an increased risk mortality worldwide. Peroxisome proliferator–activated receptor delta (PPARδ) has been shown to modulate vascular smooth muscle cell (SMC) phenotypic switching, and, hence, stability. Melatonin reportedly plays a beneficial role in cardiovascular diseases; however, mechanisms underlying improvements vulnerability remain unknown. In this study, we assessed melatonin regulating SMC switching and its consequential contribution amelioration explored process. We analyzed features markers transition high‐cholesterol diet (HCD)–fed apolipoprotein E knockout ( ApoE −/− ) mice human aortic SMCs (HASMCs). reduced size necrotic core area while enhancing collagen content, fibrous cap thickness, alpha‐actin positive coverage on cap, which are all known characteristics vulnerable plaques. lesions, significantly decreased synthetic phenotype KLF4 expression PPARδ, but not PPARα PPARγ, HCD‐fed mice. These results were subsequently confirmed melatonin‐treated HASMCs. Further analysis using PPARδ silencing immunoprecipitation assays revealed that melatonin‐induced from contractile. Collectively, provided first evidence mediates protective effect against destabilization by PPARδ‐mediated thereby indicating potential treating atherosclerosis.

Язык: Английский

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Plasma Proteomic Biomarkers in Alzheimer’s Disease and Cardiovascular Disease: A Longitudinal Study

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10751 - 10751

Опубликована: Окт. 6, 2024

The co-occurrence of Alzheimer's disease (AD) and cardiovascular diseases (CVDs) in older adults highlights the necessity for exploration potential shared risk factors. A total 566 were selected from Disease Neuroimaging Initiative (ADNI) database, including 111 individuals with AD, 383 mild cognitive impairment (MCI), 410 CVD. multivariable linear mixed model (LMM) was used to investigate associations AD CVD longitudinal changes 146 plasma proteomic biomarkers (measured at baseline 12-month follow-up). LMM showed that 48 linked 46 (p < 0.05). Both associated 14 (α1Micro, ApoH, β2M, BNP, complement C3, cystatin C, KIM1, NGAL, PPP, TIM1, THP, TFF3, TM, VEGF), both MCI 12 (ApoD, AXL, Calcitonin, CD40, C-peptide, pM, TNFR2, TTR, suggesting intricate connections between decline health. Among these, Tamm Horsfall Protein (THP) MCI, CVD, APOE-ε4. This study provides valuable insights into distinct biological markers mechanisms underlying

Язык: Английский

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Atherosclerosis: From the Disruption of Mitochondrial Membrane Potential to the Potential Interventional Strategies

Current Medicinal Chemistry, Год журнала: 2022, Номер 30(38), С. 4355 - 4373

Опубликована: Дек. 5, 2022

Abstract: Atherosclerosis (AS) is the major factor of cardiovascular disease (CVD) and characterized by a progressive chronic inflammatory process in arterial wall. Recent studies have shown that disruption mitochondrial membrane potential (deltapsi (m)) directly affects electron transport chain (ETC), which turn leads to oxidative stress, furthermore, its alteration apoptosis activation NLRP3 inflammasome, thereby promoting development AS. Here, this review describes how deltapsi (m) contributes AS mediating apoptosis, inflammasome activation, intervention strategies targeting induced (m).

Язык: Английский

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Melatonin protects TEGDMA-induced preodontoblast mitochondrial apoptosis via the JNK/MAPK signaling pathway

Acta Biochimica et Biophysica Sinica, Год журнала: 2023, Номер unknown

Опубликована: Ноя. 9, 2023

Resin monomer-induced dental pulp injury presents a pathology related to mitochondrial dysfunction. Melatonin has been regarded as strong protective bioactive compound from the pineal gland. However, it remains unknown whether melatonin can prevent resin injury. The aim of this study is investigate effects on apoptosis mouse preodontoblast cells (mDPC6T) induced by triethylene glycol dimethacrylate (TEGDMA), major component in resin, and determine JNK/MAPK signaling pathway mediates effect melatonin. A well-established TEGDMA-induced mDPC6T model adopted preventive function detecting cell viability, rate, expressions apoptosis-related proteins, ROS (mtROS) production, membrane potential (MMP) adenosine triphosphate (ATP) level. Inhibitors MAPKs are used explore which involved apoptosis. Finally, role verified using JNK agonists antagonists. Our results show that attenuates reducing mtROS production rescuing MMP ATP levels. Furthermore, dysfunction alleviated only inhibitor SP600125 but not other MAPK inhibitors. Additionally, downregulates expression phosphorylated counteractes activating anisomycin pathway, mimicking SP600125. findings demonstrate protects against partly through maintenance function, offering novel therapeutic strategy for prevention

Язык: Английский

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FEATURES OF RELATIONS OF MELATONIN WITH THE STATE OF INTRACELLULAR REGULATORSOF THE FUNCTIONAL ACTIVITY OF WHOLE BLOOD MONONUCLEAR CELLS IN CORONARY HEART DISEASE

Problems of Biological Medical and Pharmaceutical Chemistry, Год журнала: 2024, Номер 27(2), С. 15 - 22

Опубликована: Фев. 2, 2024

Introduction. Coronary heart disease (CHD), leading among the causes of death in adulthood and old age, is an urgent medical social problem. The pathogenesis most forms coronary based on stenosing atherosclerosis arteries, which develops against background dyslipidemia arterial hypertension accompanied by activation immunocompetent cells (ICCs) vascular wall with development a subclinical inflammatory reaction, as well production pro-inflammatory factors such interleukins, chemokines, growth etc. In turn, ICC activity determined state their intracellular molecular cascades, transmit signals into cell ensure its reactivity to various external stimuli, mitogens, cytokines, pathogen components, etcIt has been shown that central nervous system plays important role regulation due neurohumoral molecules, melatonin, endorphin, sero-tonin, etc., coordination immune responses control system. aim this study was relationship between melatonin regulate activi-ty whole blood mononuclear metabolism patients artery disease. Material methods. As part cohort study, 58 both sexes aged 49 67 years 20 practically healthy individuals were examined. accordance purpose concentration focal adhesion protein kinase (FAK), 5'AMP-activated (AMPK), AKT1 kinase, signal transducers transcription activators (STAT) nuclear cy-toplasmic lysates cells: STAT3, STAT5A STAT6, c-Jun N-terminal 1 2 isoforms (JNK), mitogen-activated p38 (p38), extracellular (ERK), Janus type (JAK2), factor NF -kB, caspase-1, cyclooxygenase-2 (COX-2), p70-S6K1 p53, p27, p21 proteins. addition, cyclic adenosine monophos-phate (cAMP) guanosine monophosphate (cGMP) supernatants. Melatonin se-rum. material for venous taken from cubital vein morning 6.00 6.15. Results. analysis showed disease, comparison individuals, MNCs blood, there increased level kinases FAK, AKT, JNK, ERK, p70-S6K1, p21, decrease content STAT5A, JAK2, NF-kB caspase-1. These changes levels cGMP cAMP. Against background, revealed MNC. A high CAD as-sociated AMPK, Jak2, ERK1, cAMP MNCs, observed increase p27 NF-kB. results correlation indicate different na-ture protein, depending characteristics Conclusions. exhibits modulating effect energy balance ICCs metabolism, helps limit limiting functional MAPK/SAPK signaling pathways MNCs.

Язык: Английский

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