Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: April 13, 2023

Abstract Among the complications of diabetes, cardiovascular events and cardiac insufficiency are considered two most important causes death. Experimental clinical evidence supports effectiveness SGLT2i for improving dysfunction. treatment benefits metabolism, microcirculation, mitochondrial function, fibrosis, oxidative stress, endoplasmic reticulum programmed cell death, autophagy, intestinal flora, which involved in diabetic cardiomyopathy. This review summarizes current knowledge mechanisms Graphical

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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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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Inflammation: A New Look at an Old Problem

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4596 - 4596

Published: April 21, 2022

Pro-inflammatory stress is inherent in any cells that are subject to damage or threat of damage. It defined by a number universal components, including oxidative stress, cellular response DNA damage, unfolded protein mitochondrial and endoplasmic reticulum changes autophagy, inflammasome formation, non-coding RNA response, formation an inducible network signaling pathways, epigenetic changes. The presence receptor secretory phenotype many the cause tissue pro-inflammatory stress. key phenomenon determining occurrence classical inflammatory focus microvascular (exudation, leukocyte migration alteration zone). This same reaction at systemic level leads development life-critical inflammation. From this standpoint, we can characterize common mechanisms pathologies differ their clinical appearance. division inflammation into alternative variants has deep evolutionary roots. Evolutionary aspects also described review. aim review provide theoretical arguments for need up-to-date theory relationship between human pathological processes based on integrative role molecular

Language: Английский

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The Role of Peritoneal Macrophages in Endometriosis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(19), P. 10792 - 10792

Published: Oct. 6, 2021

Endometriosis is an estrogen-dependent gynecological disorder, defined as the growth of endometrial stromal cells and glands at extrauterine sites. Endometriotic lesions are more frequently located into abdominal cavity, although they can also be implanted in distant places. Among its etiological factors, presence immune dysregulation occupies a prominent place, pointing out beneficial harmful outcomes macrophages pathogenesis this disease. Macrophages tissue-resident that connect innate adaptive immunity, playing key role maintaining local homeostasis healthy conditions being critical development sustainment many inflammatory diseases. accumulate peritoneal cavity women with endometriosis, but their ability to clear migrated fragments seems inefficient. Hence, characteristics system endometriosis must further studied facilitate search for new diagnostic therapeutic tools. In review, we summarize recent relevant advances obtained both mouse, main animal model used study human, focusing on from endometriotic patients donors, under perspective future clinical translation these play pathology.

Language: Английский

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CD36 as a gatekeeper of myocardial lipid metabolism and therapeutic target for metabolic disease

Physiological Reviews, Journal Year: 2023, Volume and Issue: 104(2), P. 727 - 764

Published: Oct. 26, 2023

The multifunctional membrane glycoprotein CD36 is expressed in different types of cells and plays a key regulatory role cellular lipid metabolism, especially cardiac muscle. facilitates the uptake long-chain fatty acids, mediates signaling, regulates storage oxidation lipids various tissues with active metabolism. deficiency leads to marked impairments peripheral which consequently impact on utilization multiple fuels because integrated nature functional presence at plasma regulated by its reversible subcellular recycling from endosomes under control mechanical, hormonal, nutritional factors. Aberrations this dynamic are causally associated metabolic diseases, particular insulin resistance, diabetic cardiomyopathy, hypertrophy. Recent research muscle has disclosed endosomal proton pump vacuolar-type H

Language: Английский

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Assessing platelet-derived extracellular vesicles for potential as therapeutic targets in cardiovascular diseases

Expert Opinion on Therapeutic Targets, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: Jan. 16, 2025

Introduction Cardiovascular disease (CVD) is the leading cause of death worldwide. Platelet-derived extracellular vesicles (PEV) have attracted extensive attention in cardiovascular research recent years because their cargo involved a variety pathophysiological processes, such as thrombosis, immune response, promotion or inhibition inflammatory angiogenesis well cell proliferation and migration.

Language: Английский

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Inhibition of CD36 ameliorates mouse spinal cord injury by accelerating microglial lipophagy

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Language: Английский

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Lipid-induced S-palmitoylation as a Vital Regulator of Cell Signaling and Disease Development

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(15), P. 4223 - 4237

Published: Jan. 1, 2021

Lipid metabolites are emerging as pivotal regulators of protein function and cell signaling.The availability intracellular fatty acid is tightly regulated by glycolipid metabolism may affect human body through many biological mechanisms.Recent studies have demonstrated palmitate, either from exogenous uptake or de novo synthesis, serve the substrate for palmitoylation regulate via palmitoylation.Palmitoylation, most-studied lipidation, encompasses reversible covalent attachment palmitate moieties to cysteine residues.It controls various cellular physiological processes alters stability, conformation, localization, membrane association interaction with other effectors.Dysregulation has been implicated in a plethora diseases, such metabolic syndrome, cancers, neurological disorders infections.Accordingly, it could be one molecular mechanisms underlying impact metabolite on homeostasis diseases.Herein, we explore relationship between lipid regulation palmitoylation.We review current progress made putative role altering key proteins thus contributing pathogenesis among which focus disorders, inflammation infections, neurodegenerative diseases.We also highlight opportunities new therapeutics target disease development.

Language: Английский

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Lipid scavenging macrophages and inflammation

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2021, Volume and Issue: 1867(1), P. 159066 - 159066

Published: Oct. 8, 2021

Macrophages are professional phagocytes, indispensable for maintenance of tissue homeostasis and integrity. Depending on their resident tissue, macrophages exposed to highly diverse metabolic environments. Adapted niche, they can contribute local turnover through metabolite uptake, conversion, storage release. Disturbances in caused by infection, inflammation or damage dramatically alter the milieu, impacting macrophage activation status metabolism. In case persisting stimuli, defective responses ensue, which promote disease. Especially relevant herein disbalances lipid rich environments, where crucially involved uptake turnover, preventing lipotoxicity. Lipid is a large extent facilitated expressed scavenger receptors that dynamically regulated important many diseases. Here, we review mediating summarize recent findings role health We further highlight underlying pathways driving acquisition impact myeloid remodelling.

Language: Английский

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