GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease

Nature Reviews Endocrinology, Journal Year: 2021, Volume and Issue: 17(10), P. 592 - 607

Published: Aug. 11, 2021

Language: Английский

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Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 2, 2022

Abstract Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases, such as cardiovascular diseases (CVD), neurodegenerative and cancers, particularly CVD which accumulation lipids (mainly cholesteryl esters) within macrophage/foam cells underneath endothelial layer drives formation atherosclerotic lesions eventually. More more studies have shown that lowering level, especially low-density lipoprotein protects system prevents events effectively. Maintaining is determined by biosynthesis, uptake, efflux, transport, storage, utilization, and/or excretion. All processes should be precisely controlled regulatory pathways. Based on regulation homeostasis, many interventions been developed to lower inhibiting biosynthesis uptake or enhancing utilization Herein, we summarize historical review research events, current understandings molecular pathways playing key regulating cholesterol-lowering clinics preclinical well new targets their clinical advances. importantly, discuss benefits those for treatment including obesity, diabetes, nonalcoholic fatty liver disease, cancer, osteoporosis virus infection.

Language: Английский

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Naringenin and naringin in cardiovascular disease prevention: A preclinical review

European Journal of Pharmacology, Journal Year: 2020, Volume and Issue: 887, P. 173535 - 173535

Published: Sept. 8, 2020

Language: Английский

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Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: June 1, 2022

Atherosclerosis is an immuno-metabolic disease involving chronic inflammation, oxidative stress, epigenetics, and metabolic dysfunction. There compelling evidence suggesting numerous modifications including the change of size, density, biochemical properties in low-density lipoprotein (LDL) within vascular wall. These LDL, addition to LDL transcytosis retention, contribute initiation, development clinical consequences atherosclerosis. Among different atherogenic oxidation represents a primary modification. A series pathophysiological changes caused by oxidized (oxLDL) enhance formation foam cells atherosclerotic plaques. OxLDL also promotes fatty streaks atherogenesis through induction endothelial dysfunction, cells, monocyte chemotaxis, proliferation migration SMCs, platelet activation, which culminate plaque instability ultimately rupture. This article provides concise review oxLDL, enzymes mediating oxidation, receptors pro-atherogenic signaling pathways oxLDL cells. The explores how functions stages dysfunction Future targeted therapies aiming at reducing and/or lowering levels oxLDL-mediated pro-inflammatory responses are discussed.

Language: Английский

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Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review

Acta Pharmacologica Sinica, Journal Year: 2022, Volume and Issue: 43(9), P. 2173 - 2190

Published: Jan. 19, 2022

Language: Английский

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Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 1, 2024

Abstract Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, inflammation. Accumulating evidence has shown that implicated in diseases, such as cancers, cardiac diseases cardiovascular neurological disorders, kidney motor system metabolic disorders. Examining the upstream modulators co-activated partners identifying critical biological events modulated by downstream effectors contribute to presentation elaborate network PGC-1s. Furthermore, discussing correlation between well summarizing therapy targeting helps make individualized precise intervention methods. In this review, we summarize basic knowledge regarding molecular regulatory network, discuss physio-pathological roles human review application PGC-1s, diagnostic prognostic value several therapies pre-clinical studies, suggest directions for future investigations. This presents immense potential treatment hopefully facilitates promotion new therapeutic targets.

Language: Английский

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Inflammatory Cells in Atherosclerosis

Antioxidants, Journal Year: 2022, Volume and Issue: 11(2), P. 233 - 233

Published: Jan. 26, 2022

Atherosclerosis is a chronic progressive disease that involves damage to the intima, inflammatory cell recruitment and accumulation of lipids followed by calcification plaque rupture. Inflammation considered key mediator many events during development progression disease. Various types cells are reported be involved in atherosclerosis. In present paper, we discuss cells, their characteristic functional significance The detailed understanding role all these at different stages sheds more light on subject provides valuable insights as where when therapy should targeted.

Language: Английский

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TREM2 promotes cholesterol uptake and foam cell formation in atherosclerosis

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(5)

Published: May 1, 2023

Language: Английский

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Mechanisms of wogonoside in the treatment of atherosclerosis based on network pharmacology, molecular docking, and experimental validation

BMC Complementary Medicine and Therapies, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 27, 2025

Atherosclerosis serves as the fundamental pathology for a variety of cardiovascular disorders, with its pathogenesis being closely tied to complex interplay among lipid metabolism, oxidative stress, and inflammation. Wogonoside is natural flavonoid extracted from Scutellaria baicalensis biological activities, including anti-inflammatory, hypolipidemic, cardiac function improvement properties. Despite these known effects, specific role wogonoside in context atherosclerosis remains be elucidated. To validate efficacy treatment investigate possible therapeutic mechanisms. Network pharmacology was used obtain core targets signaling pathways that may efficacious wogonoside, which were validated using molecular docking dynamics simulations. further pathway, we performed vivo experiments apolipoprotein E (ApoE)-/- mice. This included pathological morphology deposition analysis mouse aorta, serum level analysis, Elisa stress reactive oxygen species (ROS) fluorescence assay, immunohistochemical protein blot analysis. Predictions obtained has 31 targets, are mainly focused on such Toll-like receptor (TLR) pathway NF-kappa B (NF-κB ) pathway. Molecular simulations showed good binding properties targets. In experimental results significantly inhibited aortic inflammatory response deposition, reduced release levels total cholesterol (TC), triglycerides (TG), low-density-lipoprotein (LDL-C), oxidized low density (ox-LDL) free fatty acid (FFA), factors TNF-α, IL-1β, IL-6 ApoE-/- Further mechanism studies activation TLR4/NF-κB an effective drug monomer atherosclerosis, action related inhibition

Language: Английский

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Impact of sodium glucose cotransporter 2 (SGLT2) inhibitors on atherosclerosis: from pharmacology to pre-clinical and clinical therapeutics

Theranostics, Journal Year: 2021, Volume and Issue: 11(9), P. 4502 - 4515

Published: Jan. 1, 2021

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are new oral drugs for the therapy of patients with type diabetes mellitus (T2DM).Research in past decade has shown that SGLT2i class, such as empagliflozin, canagliflozin, and dapagliflozin, have pleiotropic effects preventing cardiovascular diseases beyond their favorable impact on hyperglycemia.Of clinical relevance, recent landmark outcome trials demonstrated reduce major adverse events, hospitalization heart failure, death T2DM with/without (including atherosclerotic various types failure).The pharmacological action is through inhibiting glucose re-absorption kidney thus promoting excretion.Studies experimental models atherosclerosis ameliorate progression by mechanisms including inhibition vascular inflammation, reduction oxidative stress, reversing endothelial dysfunction, reducing foam cell formation platelet activation.Here, we summarize anti-atherosclerotic actions SGLT2i, an aim to emphasize utility this class agents insidious complications accompanying diabetes.

Language: Английский

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