Vascular ATGL-dependent lipolysis and the activation of cPLA2–PGI2 pathway protect against postprandial endothelial dysfunction

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: March 12, 2024

Abstract Adipose triglyceride lipase (ATGL) is involved in lipolysis and displays a detrimental pathophysiological role cardio-metabolic diseases. However, the organo-protective effects of ATGL-induced were also suggested. The aim this work was to characterize function lipid droplets (LDs) regulation endothelial function. ATGL-dependent LDs hydrolysis cytosolic phospholipase A 2 (cPLA )-derived eicosanoids production studied aorta, smooth muscle cells exposed exogenous oleic acid (OA) or arachidonic (AA). Functional subsequent activation cPLA /PGI pathway vivo relation postprandial dysfunction. formation invariably associated with elevated endogenous AA-derived prostacyclin (PGI ). In presence inhibitor ATGL , reduced, concomitant increase number LDs. OA administration impaired barrier integrity vitro that further if given together inhibitor. Importantly, vivo, olive oil induced dysfunction significantly deteriorated by inhibition, inhibition (IP) receptor blockade. summary, vascular AA ATGL- -dependent PGI from AA. resulted an impairment . ATGL-cPLA -PGI dependent deterioration upon exposure vivo. conclusion, activated overload linked endothelium has vasoprotective counterbalancing on

Language: Английский

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Metabolic Dysfunction-Associated Steatotic Liver Disease: Pathogenetic Links to Cardiovascular Risk

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 163 - 163

Published: Jan. 22, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is correlated with an increased cardiovascular risk, independent of other traditional risk factors. The mechanisms underlying this pathogenic link are complex yet remain incompletely elucidated. Among these, the most significant visceral adiposity, low-grade inflammation and oxidative stress, endothelial dysfunction, prothrombotic status, insulin resistance, dyslipidemia postprandial hyperlipemia, gut dysbiosis, genetic mutations. Cardiovascular diseases leading cause death in patients MASLD. These have incidence coronary artery disease, carotid structural functional cardiac abnormalities, valvulopathies, as well arrhythmias conduction disorders. In review, we present latest data on association between MASLD focusing that explain correlation these two pathologies. Given high rates morbidity mortality among MASLD, consider it imperative to raise awareness risks associated condition within general population. Further research essential clarify linked This understanding may facilitate identification new diagnostic prognostic biomarkers for patients, novel therapeutic targets.

Language: Английский

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Conditional knockdown of hepatic PCSK9 ameliorates high-fat diet-induced liver inflammation in mice

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

Instruction Accumulating evidence has shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with inflammation in the vascular system. However, roles of PCSK9 hepatic remain unclear. Because mainly expressed liver and modulates lipid uptake through low-density lipoprotein receptor family members, present study aimed to elucidate effect conditional knockdown on hyperlipidemia-induced underlying mechanisms action. Methods PCSK9flox/flox mice were bred ALB-Cre + obtain (−/−) , (+/−) (+/+) mice. These fed a high-fat diet for weeks induce inflammation. The effects investigated by molecular biological techniques. Moreover, findings verified vitro using HepG2 cells. Results Discussion Conditional remarkably decreased plasma levels total cholesterol alleviated injury. Mechanistically, significantly reduced pro-inflammatory factors downregulating expression Toll-like receptors, mitogen-activated protein kinase (MAPK), phosphoinositide-3 kinase/protein B, which subsequently attenuated downstream molecules, namely nuclear factor kappa-B activator protein-1. related confirmed lipid-loaded cells together siRNA, alirocumab (anti-PCSK9 antibody), and/or p38-MAPK inhibitor. attenuates following hyperlipidemia induction modulating multiple signaling pathways; this suggests targeting knockdown/inhibition appropriate agents useful not only treating but also ameliorating

Language: Английский

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Combined and mediating effects of remnant cholesterol and renal function on hypertension risk in Chinese middle-aged and elderly people

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 13, 2025

Background Emerging evidence indicates a potential correlation between remnant cholesterol (RC) and the development of vascular damage hypertension. Nevertheless, precise relationship RC hypertension in relation to renal function remains uncertain. The objective this investigation was employ cohort design evaluate intricate Methods present utilized data from China Health Retirement Longitudinal Study (CHARLS), encompassing total 5,109 participants, for comprehensive analysis examination. Cox regression employed examine interplay among RC, function, within context research study. This study restricted cubic spline (RCS) elucidate interaction hypertension, specifically examining mediating role RC-hypertension nexus. Furthermore, we mediation investigate association Results After 9-year follow-up period, incidence population under observed be 19.01%. Kaplan-Meier curves demonstrated notable statistically significant elevation prevalence subgroup characterized by higher impaired (P <0.001). However, analyses, risk developing significantly ( P < 0.05) those with high estimated glomerular filtration rate (eGFR), low eGFR, compared after adjusting confounders. RCS positive linear baseline Additionally, there negative eGFR levels did not interact any variables. lowering mediated 6% associations Conclusion findings unveiled substantial elevated diminished levels, In addition, may mediate risk.

Language: Английский

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Molecular mechanisms underlying some major common risk factors of stroke

Heliyon, Journal Year: 2022, Volume and Issue: 8(8), P. e10218 - e10218

Published: Aug. 1, 2022

Ischemic and hemorrhagic strokes are the most common known cerebrovascular disease which can be induced by modifiable non-modifiable risk factors. Age race factors of stroke. However, hypertension, diabetes, obesity, dyslipidemia, physical inactivity, cardiovascular disorders major Understanding molecular mechanism mediating each these is expected to contribute significantly reducing stroke, preventing neural damage, enhancing rehabilitation, designing suitable treatments. Abnormalities in structure blood-brain barrier blood vessels, thrombosis, vasoconstriction, atherosclerosis, reduced cerebral flow, oxidative stress, inflammation, apoptosis, impaired synaptic transmission, excitotoxicity, altered expression/activities many channels signaling proteins knows mechanisms responsible for stroke induction. role not well understood requires a lot search reading. This review was designed provide reader with single source information that discusses current update prevalence, pathophysiology, all possible underlying some namely, diabetes mellitus, lipid fraction, inactivity. provides full resource understanding effect

Language: Английский

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Postprandial Metabolic and Oxidative Stress Responses to Grape Pomace Extract in Healthy Normal and Overweight/Obese Women: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

Nutrients, Journal Year: 2022, Volume and Issue: 15(1), P. 156 - 156

Published: Dec. 29, 2022

Postprandial oxidative stress has been shown to promote atherosclerosis. Grape pomace (GP) is a source of similar-to-wine bioactive micro-constituents with known antioxidant properties. The aim the present study was evaluate metabolic and responses after intake grape extract along high-fat meal, in normal overweight healthy women. In randomized, double-blind, placebo-controlled crossover study, 18 women were finally included, 11 BMI < 25 kg/m2 7 > kg/m2, consumed meal placebo or GP capsules two separate visits. Blood samples collected before 6 h consumption. Measurements included basic biochemical markers, uric acid (UA), protein carbonyls (PC), thiobarbituric substance (TBARS) levels, as well superoxide dismutase (SOD) glutathione peroxidase (GPx) activities. At certain time points, consumption normal-weight reduced UA, TBARS SOD activity, whereas it increased UA PC levels overweight/obese women, compared placebo. GP-derived compounds may exert actions during postprandial state through different mechanisms according their status.

Language: Английский

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Food Compass Score and its association with inflammatory markers and homocysteine in cardiovascular disease-free adults: a cross-sectional analysis of the ATTICA epidemiological study

European Journal of Clinical Nutrition, Journal Year: 2023, Volume and Issue: 77(10), P. 998 - 1004

Published: July 3, 2023

Language: Английский

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Effective, disease-modifying, clinical approaches to patients with mild-to-moderate hypertriglyceridaemia

The Lancet Diabetes & Endocrinology, Journal Year: 2021, Volume and Issue: 10(2), P. 142 - 148

Published: Dec. 16, 2021

Language: Английский

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The Association of Remnant Cholesterol with Endothelial Dysfunction and Subclinical Atherosclerosis in a Check-Up Population in China

Journal of Atherosclerosis and Thrombosis, Journal Year: 2022, Volume and Issue: 30(6), P. 684 - 697

Published: Sept. 12, 2022

Vascular endothelial function and atherosclerosis are known to be important risk factors for cardiovascular disease. However, it remains unknown whether remnant cholesterol (RC) correlates with vascular as represented by flow-mediated vasodilation (FMD) brachial-ankle pulse wave velocity (baPWV). Therefore, in this study, we aimed investigate the general population.

Language: Английский

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Pancreatic and cardiometabolic complications of severe hypertriglyceridaemia

Current Opinion in Lipidology, Journal Year: 2024, Volume and Issue: 35(4), P. 208 - 218

Published: June 6, 2024

Purpose of review This endeavours to explore the aetiopathogenesis and impact severe hypertriglyceridemia (SHTG) chylomicronaemia on cardiovascular, pancreatic complications summarizes novel pharmacological options for management. Recent findings SHTG, although rare, presents significant diagnostic therapeutic challenges. Familial syndrome (FCS), is rare monogenic form associated with increased acute pancreatitis (AP) risk, whereas relatively common multifactorial (MCS) leans more towards cardiovascular complications. Despite introduction validation FCS Score, continues be underdiagnosed diagnosis often delayed. Longitudinal data disease progression remains scant. SHTG-induced AP a life-threatening concern, conservative treatment as cornerstone while blood purification techniques offer limited additional benefit. Conventional lipid-lowering medications exhibit minimal efficacy, underscoring growing interest in avenues, that is, antisense oligonucleotides (ASO) short interfering RNA (siRNA) targeting apolipoprotein C3 (ApoC3) angiopoietin-like protein 3 and/or 8 (ANGPTL3/8). Summary advancements understanding genetic basis pathogenesis challenges persist. The rarity heterogenous phenotype MCS underscore need development predictive models tailored personalized strategies. establishment national international registries advocated augment comprehension identify high-risk individuals.

Language: Английский

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