Nitric Oxide Signaling and Regulation in the Cardiovascular System: Recent Advances

Pharmacological Reviews, Год журнала: 2024, Номер 76(6), С. 1038 - 1062

Опубликована: Июнь 12, 2024

Nitric oxide (NO) from endothelial NO synthase (eNOS) importantly contributes to vascular homeostasis. Reduced production or increased scavenging during disease conditions with oxidative stress contribute dysfunction and deficiency. In addition the classical enzymatic NOS system, can also be generated via nitrate-nitrite-NO pathway. Dietary pharmacological approaches aimed at increasing bioactivity, especially in cardiovascular have been focus of much research since discovery this small gaseous signaling molecule. Despite wide appreciation biological role NOS/NO signaling, questions still remain about chemical nature NOS-derived bioactivity. Recent studies show that NO-like bioactivity efficiently transduced by mobile NO-ferroheme species which transfer between proteins, partition into a hydrophobic phase, directly activate sGC-cGMP-PKG pathway without intermediacy free NO. Moreover, interaction red blood cells endothelium regulation homeostasis gained attention, cardiometabolic disease. review we discuss both non-classical pathways for generation how these modulated therapeutic purposes. Significance Statement After four decades intensive research, persist transduction control Here health disease, highlighting new findings, such as important Non-classical modes, like pathway, opportunities related system are discussed. Existing potential treatments/strategies, well dietary components influencing covered.

Язык: Английский

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The pleiotropic effects of statins: a comprehensive exploration of neurovascular unit modulation and blood–brain barrier protection

Molecular Medicine, Год журнала: 2024, Номер 30(1)

Опубликована: Дек. 20, 2024

Abstract The blood–brain barrier (BBB) is the most central component of neurovascular unit (NVU) and crucial for maintenance internal environment nervous system regulation homeostasis. A multitude neuroprotective agents have been developed to exert effects improve prognosis patients with ischemic stroke. These designed maintain integrity promote BBB repair. Statins are widely used as pharmacological treatment prevention stroke, making them a cornerstone in armamentarium this condition. primary mechanism action reduction serum cholesterol through inhibition 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase, which results decrease low-density lipoprotein (LDL-C) an increase clearance. Nevertheless, basic clinical research has indicated that statins may additional pleiotropic beyond LDL-C reduction. Previous studies on stroke demonstrated can enhance neurological function, reduce inflammation, angiogenic synaptic processes following increasingly recognized its role development progression also found play potential protective by affecting members NVU. This review aimed provide comprehensive theoretical basis application systematically detailing how influence BBB, particularly focusing function each member Graphical

Язык: Английский

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Endothelin receptor antagonists (ERAs) can potentially be used as therapeutic drugs to reduce hypertension caused by small molecule tyrosine kinase inhibitors (TKIs)

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 9, 2025

The emergence of targeted anti-tumor drugs has significantly prolonged the lifespan and improved prognosis cancer patients. Among these drugs, vascular endothelial growth factor (VEGF) inhibitors, particularly novel small molecule tyrosine kinase inhibitors (TKIs), are extensively employed as VEGF inhibitors; however, they also associated with a higher incidence complications, hypertension being most prevalent cardiovascular toxic side effect. Currently, it is widely accepted that TKIs-induced involves multiple mechanisms including dysregulation endothelin (ET) axis, reduced bioavailability nitric oxide (NO), imbalance in NO-ROS equilibrium system, rarefaction, activation epithelial sodium calcium channels; nevertheless, excessive ET system appears to be predominantly responsible for this condition. Moreover, studies have demonstrated plays pivotal role driving hypertension. Therefore, review aims explore significance pathogenesis induced by investigate potential therapeutic value antagonists managing caused drugs.

Язык: Английский

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Atypical antipsychotics impair the lipid-lowering and pleiotropic effects of simvastatin via activation of the ADMA-NOX-ROS pathway

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 185, С. 117958 - 117958

Опубликована: Март 8, 2025

Язык: Английский

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Endothelial miR-34a deletion guards against aneurysm development despite endothelial dysfunction

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер unknown, С. 167812 - 167812

Опубликована: Март 1, 2025

Язык: Английский

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Cerebral Small Vessel Disease: Therapeutic Approaches Targeting Neuroinflammation, Oxidative Stress, and Endothelial Dysfunction

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(4), С. 232 - 232

Опубликована: Март 27, 2025

Cerebral small vessel disease (cSVD) is a common cause of stroke and dementia. Ageing, hypertension, hyperglycaemia, smoking make up the biggest risk factors for cSVD. They individually or collectively increase levels reactive oxygen species, pro-inflammatory cytokines matrix metalloproteinases, decrease bioavailability nitric oxide, and, in process, compromise structural integrity function vascular endothelium, blood–brain barrier, brain parenchyma. These then appear as white matter hyperintensities, enlarged perivascular spaces, cerebral microbleeds, atrophy imaging. As there currently no curative therapy cSVD, prevention delay cSVD remains particular importance to preserve quality life long possible. Bearing that mind, this review explores whether drugs used other neurovascular conditions may prevent neuroinflammation oxidative damage effectively maintain endothelial barrier integrity. It also examines potential benefits be extended The list includes anti-anginal drugs, acetylcholine esterase inhibitors, β-hydroxy β-methylglutaryl-CoA reductase lithium phosphodiesterase oral antihyperglycaemic tetracycline antibiotics. This discusses mechanisms action these agents critically evaluates preclinical, translational, clinical research pertaining

Язык: Английский

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Enhancement of Solubility and Bioavailability of Bezafibrate Based on Hydrotropy and Solid Dispersion Technique

Journal of Pharmaceutical Innovation, Год журнала: 2025, Номер 20(2)

Опубликована: Апрель 1, 2025

Язык: Английский

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Nanoparticles constructed from natural polyphenols are used in acute kidney injury

Journal of Materials Chemistry B, Год журнала: 2024, Номер 12(36), С. 8883 - 8896

Опубликована: Янв. 1, 2024

Acute kidney injury (AKI) is a severe clinical syndrome characterized by rapid deterioration of renal function caused variety pathogeneses.

Язык: Английский

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Myocardial Expression of Pluripotency, Longevity, and Proinflammatory Genes in the Context of Hypercholesterolemia and Statin Treatment

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(7), С. 1994 - 1994

Опубликована: Март 29, 2024

Background: This study sought to assess the effect of statin therapy on myocardial inflammation in a White New Zealand rabbit model atherogenesis. Methods: The mRNA expression levels pro-inflammatory, pluripotency, and aging-related markers were quantified following controlled feeding protocol treatments. Results: Following high-cholesterol diet induction, we observed significant upregulation MYD88, NF-κB, chemokines (CCL4, CCL20, CCR2), IFN-γ, interleukins (IL-1β, IL-2, IL-4, IL-8, IL-10, IL-18), novel (klotho, KFL4, NANOG, HIF1α). In contrast, HOXA5 was diminished hyperlipidemic diet. Both treatments significantly influenced studied. Nevertheless, rosuvastatin administration resulted greater reduction NF-kB, IL-1β, KLF4, HIF1α than fluvastatin. Fluvastatin, other hand, led stronger decrease IL-4. Downregulation IL-2 IL-18 IFNβ comparable between two statins. Notably, had klotho IL-10. Conclusion: Overall, attenuated inflammatory, tissue under atherogenic conditions. Our findings also highlight differential efficacy over fluvastatin curtailing proatherogenic inflammation, which could have profound implications for clinical management cardiovascular disease.

Язык: Английский

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The effect of supplementation of vitamin D on hyperlipidemia and bone mass in the pediatric with obesity

Critical Reviews in Immunology, Год журнала: 2024, Номер 45(1), С. 31 - 39

Опубликована: Апрель 25, 2024

The objective of this study was to provide guidelines clinicians for the evaluation, treatment, and prevention vitamin D deficiency with an emphasis on care patients who are at risk obesity diabetes. Our aim determine relationship between D3 metabolic syndrome, investigate effect supplementation hyperlipidemia, glucose metabolism, bone mass in pediatric obesity. We conducted a January 2018 2020, total 723 children invited participate. Of these, 283 were supplement group (SG) 440 placebo (PG). evaluated blood pressure, fasting glucose, high-density lipoprotein, cholesterol, low-density mineral density (BMD) all subjects. observed that triglyceride, levels strongly associated 25(OH)D3 baseline. After supplementation, we significant increase body index (BMI) (P = 0.02) serum < 0.01) compared group. Additionally, lipids such as cholesterol <0.01), HDL-c 0.01), cholesterol/HDL-c LDL-c/HDL-c triglycerides/HDL-c significantly decreased Serum inversely triglycerides, glucose. results suggest enhances beneficial

Язык: Английский

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