Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases

Antioxidants, Год журнала: 2025, Номер 14(3), С. 256 - 256

Опубликована: Фев. 23, 2025

Endothelial dysfunction (ED) is characterized by an imbalance between vasodilatory and vasoconstrictive factors, leading to impaired vascular tone, thrombosis, inflammation. These processes are critical in the development of cardiovascular diseases (CVDs) such as atherosclerosis, hypertension ischemia/reperfusion injury (IRI). Reduced nitric oxide (NO) production increased oxidative stress key contributors ED. Aging further exacerbates ED through mitochondrial oxidative/nitrosative stress, heightening CVD risk. Antioxidant systems like superoxide-dismutase (SOD), glutathione-peroxidase (GPx), thioredoxin/thioredoxin-reductase (Trx/TXNRD) pathways protect against stress. However, their reduced activity promotes ED, vulnerability IRI. Metabolic syndrome, comprising insulin resistance, obesity, hypertension, often accompanied Specifically, hyperglycemia worsens endothelial damage promoting Obesity leads chronic inflammation changes perivascular adipose tissue, while associated with increase The NLRP3 inflammasome plays a significant role being triggered factors reactive oxygen nitrogen species, ischemia, high glucose, which contribute inflammation, injury, exacerbation Treatments, N-acetyl-L-cysteine, SGLT2 or inhibitors, show promise improving function. Yet complexity suggests that multi-targeted therapies addressing metabolic disturbances essential for managing CVDs syndrome.

Язык: Английский

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Dapagliflozin mitigates cellular stress and inflammation through PI3K/AKT pathway modulation in cardiomyocytes, aortic endothelial cells, and stem cell-derived β cells

Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)

Опубликована: Окт. 29, 2024

Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is well-recognized for its therapeutic benefits in type diabetes (T2D) and cardiovascular diseases. In this comprehensive vitro study, we investigated DAPA's effects on cardiomyocytes, aortic endothelial cells (AECs), stem cell-derived beta (SC-β), focusing impact hypertrophy, inflammation, cellular stress. Our results demonstrate that DAPA effectively attenuates isoproterenol (ISO)-induced hypertrophy reducing cell size improving structure. Mechanistically, mitigates reactive oxygen species (ROS) production inflammation by activating the AKT pathway, which influences downstream markers of fibrosis, inflammation. Additionally, modulation SGLT2, Na+/H + exchanger 1 (NHE1), glucose transporter (GLUT 1) highlights critical role maintaining ion balance metabolism, providing insights into cardioprotective mechanisms. exhibited notable anti-inflammatory properties restoring phosphoinositide 3-kinase (PI3K) expression, enhancing mitogen-activated protein kinase (MAPK) activation, downregulating inflammatory cytokines at both gene levels. Furthermore, alleviated tumor necrosis factor (TNFα)-induced stress responses while nitric oxide synthase (eNOS) suggesting potential to preserve vascular function improve health. Investigating SC-β cells, found enhances insulin functionality without altering identity, indicating management. also upregulated MAFA, PI3K, NRF2 positively influencing β-cell response. it attenuated NLRP3 activation reduced NHE1 glucose-regulated GRP78 offering novel stress-modulating effects. Overall, our findings elucidate multifaceted across various models, emphasizing mitigating through pathway other signaling cascades. These mechanisms may not only contribute enhanced cardiac but underscore address metabolic dysregulation T2D.

Язык: Английский

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Integrating Microfluidics, Hydrogels, and 3D Bioprinting for Personalized Vessel-on-a-Chip Platforms

Biomaterials Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Advancement of vascular models from simple 2D culture to complex vessel-on-a-chip platforms through integration microfluidics, biomimetic hydrogels, and 3D bioprinting, enabling controlled investigation thrombosis mechanisms.

Язык: Английский

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Lung injury in myocardial infarction-associated cardiogenic shock supported by venoarterial extracorporeal membrane oxygenation: a scoping review

BMC Cardiovascular Disorders, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 23, 2025

Язык: Английский

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Intracellular endothelial cell metabolism in vascular function and dysfunction

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Endothelial cells (ECs) form the inner lining of blood vessels that is crucial for vascular function and homeostasis. They regulate tone, oxidative stress, permeability. Dysfunction leads to increased permeability, leukocyte adhesion, thrombosis. ECs undergo metabolic changes in conditions such as wound healing, cancer, atherosclerosis, diabetes, can influence disease progression. We discuss recent research has revealed diverse intracellular pathways are tailored their functional needs, including lipid handling, glycolysis, fatty acid oxidation (FAO). Understanding EC signatures health will be not only basic biology but also exploited when designing new therapies target EC-related functions different diseases.

Язык: Английский

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Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia

Pharmaceuticals, Год журнала: 2025, Номер 18(1), С. 106 - 106

Опубликована: Янв. 16, 2025

Prenatal hypoxia (PH) is a key factor in the development of long-term cardiovascular disorders, which are caused by various mechanisms endothelial dysfunction (ED), including those associated with NO deficiency. This emphasizes potential therapeutic agents modulator properties, such as Thiotriazoline, Angiolin, Mildronate, and L-arginine, treatment PH. Methods: Pregnant female rats were given daily intraperitoneal dose 50 mg/kg sodium nitrite starting on 16th day pregnancy. A control group pregnant received saline instead. The resulting offspring divided into following groups: Group 1-intact rats; 2-rat pups subjected to prenatal treated physiological saline; Groups 3 6-rat exposed from 1st 30th after birth. Levels sEPCR, Tie2 tyrosine kinase, VEGF-B, SOD1/Cu-Zn SOD, GPX4, GPX1 heart's cytosolic homogenate assessed using ELISA. expression VEGF VEGF-B mRNA was analyzed via real-time polymerase chain reaction, nuclear area myocardial microvessel cells evaluated morphometrically. Results: We have shown that only two representatives this group-Angiolin Thiotriazoline-are able exert full effect indices PH decrease increase Tie-2, mRNA, Cu/ZnSOD, GPX cytosol, endotheliocyte nuclei 1- 2-month-old comparison control. Conclusions: Our results experimentally substantiate necessity early postnatal cardio- endothelioprotection modulators, taking account role NO-dependent pathogenesis system disorders neonates

Язык: Английский

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Endothelial dysfunction in cardiovascular diseases: mechanisms and in vitro models

Molecular and Cellular Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 21, 2025

Abstract Endothelial cells (ECs) are arranged side-by-side to create a semi-permeable monolayer, forming the inner lining of every blood vessel (micro and macrocirculation). Serving as first barrier for circulating molecules cells, ECs represent main regulators vascular homeostasis being able respond environmental changes, either physical or chemical signals, by producing several factors that regulate tone cellular adhesion. Healthy endothelium has anticoagulant properties prevent adhesion leukocytes platelets walls, contributing resistance thrombus formation, regulating inflammation, smooth muscle cell proliferation. Many risk cardiovascular diseases (CVDs) promote endothelial expression chemokines, cytokines, molecules. The resultant activation can lead dysfunction (ECD). In vitro models ECD allow study molecular mechanisms disease provide research platform screening potential therapeutic agents. Even though alternative available, such animal ex vivo models, in offer higher experimental flexibility reproducibility, making them valuable tool understanding pathophysiological diseases, CVDs. Therefore, this review aims synthesize currently available regarding ECD, emphasizing This work will focus on 2D culture (endothelial lines primary ECs), 3D systems (scaffold-free scaffold-based), (such organ-on-a-chip). We dissect role external stimuli—chemical mechanical—in triggering ECD.

Язык: Английский

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Human Tendon‐on‐a‐Chip for Modeling the Myofibroblast Microenvironment in Peritendinous Fibrosis

Advanced Healthcare Materials, Год журнала: 2024, Номер 14(4)

Опубликована: Ноя. 15, 2024

Understanding the myofibroblast microenvironment is critical to developing therapies for fibrotic diseases. Here development of a novel human tendon-on-a-chip (hToC) reported model this crosstalk in peritendinous adhesions, which currently lacks biological therapies. The hToC facilitates cellular and paracrine interactions between vascular component, contains endothelial cells monocytes, tissue hydrogel component that houses tendon macrophages. It found replicates some aspects vivo inflammatory phenotypes preclinical clinical samples, including activated mTOR signaling, inflammation, contraction induced by activation, cytokines secretion, transendothelial migration monocytes hydrogel. Transcriptional analysis demonstrates significant overlap enriched pathways with tenolysis activation signaling. Rapamycin suppresses inflammation phenotype hToC, provides proof-of-concept its utility as an vitro tool investigating multicellular fibrosis testing therapeutics mitigate it.

Язык: Английский

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The molecular and cellular landscape of hypertrophic cardiomyopathy phenotypes: transition from obstructive to end-stage heart failure

Journal of Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Язык: Английский

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Endothelial Dysfunction in Acute Myocardial Infarction: A Complex Association With Sleep Health, Traditional Cardiovascular Risk Factors and Prognostic Markers

Clinical Cardiology, Год журнала: 2025, Номер 48(1)

Опубликована: Янв. 1, 2025

ABSTRACT Background Endothelial function (EndFx) is a core component of cardiovascular (CV) health and cardioprotection following acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI). Hypothesis AMI patients experience endothelial dysfunction (EndDys), associated traditional CV risk factors sleep patterns. EndFx may also predict short mid‐term outcomes. Methods was assessed in 63 (56.2 ± 7.6 years) using the Endothelium Quality Index (EQI). Sleep quality quantity were evaluated objective (actigraphy) subjective (Pittsburgh questionnaire) measures. Cardiorespiratory fitness quantified through 6‐min walking test. Cardiac left ventricular ejection fraction. Results Following AMI, tended to EndDys (EQI = 1.4 0.7). A severe observed 23.8% ( n 15), while mild present 63.49% 40). Furthermore, significantly (i.e., low physical activity level [12.8%], age [−4.2%], smoking [−0.7%]) (R 2 adjusted 0.50, p < 0.001). Patients had poor 0.001) efficiency 0.016) compared healthy persons. exhibited lower cardiorespiratory those 0.017). during follow‐up period (nearly 4 months) PCI, major adverse cardiac events four EndDys. Conclusions Our results emphasize importance adequate an active lifestyle, notably practice, as modifiable elements enhance EndFx, which regarded predictive tool AMI. However, other remain be elucidated predictors risk. Trial Registration The study protocol registered Pan African Clinical Registry under trial ID: PACTR202208834230748.

Язык: Английский

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