Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society

European Heart Journal, Journal Year: 2021, Volume and Issue: 42(47), P. 4791 - 4806

Published: July 30, 2021

Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for causal association between triglycerides (TG), TG-rich lipoproteins (TRL), TRL remnants, increased risk myocardial infarction, ischaemic stroke, aortic valve stenosis. These data also indicate that their remnants may contribute significantly to residual cardiovascular patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding the structure, function, metabolism TRL, pathophysiological role atherosclerotic disease (ASCVD). Key points are (i) working definition normo- hypertriglyceridaemic states relation ASCVD, (ii) conceptual framework generation due dysregulation production, lipolysis, remodelling, as well clearance remnant from circulation, (iii) pleiotropic proatherogenic actions at arterial wall, (iv) challenges defining, quantitating, assessing atherogenic properties particles, (v) exploration relative atherogenicity compared LDL. Assessment these issues provides foundation evaluating approaches effectively reduce levels by targeting either or hepatic clearance, combination mechanisms. consensus updates an integrated manner, thereby providing platform new therapeutic paradigms aim reducing ASCVD.

Language: Английский

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Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study

European Heart Journal, Journal Year: 2021, Volume and Issue: 42(42), P. 4324 - 4332

Published: June 23, 2021

Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD.

Language: Английский

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Endothelial Dysfunction in Obesity

Advances in experimental medicine and biology, Journal Year: 2017, Volume and Issue: unknown, P. 345 - 379

Published: Jan. 1, 2017

Language: Английский

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Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol

Diabetes, Journal Year: 2016, Volume and Issue: 65(7), P. 1767 - 1778

Published: June 13, 2016

Notwithstanding the effectiveness of lowering LDL cholesterol, residual CVD risk remains in high-risk populations, including patients with diabetes, likely contributed to by non-LDL lipid abnormalities. In this Perspectives Diabetes article, we emphasize that changing demographics and lifestyles over past few decades have resulted an epidemic “atherogenic dyslipidemia complex,” main features which include hypertriglyceridemia, low HDL cholesterol levels, qualitative changes particles, accumulation remnant lipoproteins, postprandial hyperlipidemia. We briefly review underlying pathophysiology form dyslipidemia, particular its association insulin resistance, obesity, type 2 marked atherogenicity condition. explain failure existing classes therapeutic agents such as fibrates, niacin, cholesteryl ester transfer protein inhibitors are known modify components atherogenic complex. Finally, discuss targeted repurposing therapies promising new strategies postulate targeting central abnormality complex, elevation triglyceride-rich lipoprotein represents a frontier prevention is prove most effective strategy correcting aspects thereby preventing events.

Language: Английский

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Metabolism of triglyceride-rich lipoproteins in health and dyslipidaemia

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 19(9), P. 577 - 592

Published: March 22, 2022

Language: Английский

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Addressing dyslipidemic risk beyond LDL-cholesterol

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(1)

Published: Jan. 3, 2022

Despite the success of LDL-lowering drugs in reducing cardiovascular disease (CVD), there remains a large burden residual due part to persistent dyslipidemia characterized by elevated levels triglyceride-rich lipoproteins (TRLs) and reduced HDL. This form is increasing globally as result rising prevalence obesity metabolic syndrome. Accumulating evidence suggests that impaired hepatic clearance cholesterol-rich TRL remnants leads their accumulation arteries, promoting foam cell formation inflammation. Low HDL may associate with cholesterol efflux from cells, aggravating atherosclerosis. While fibrates fish oils reduce TRL, they have not been uniformly successful CVD, unmet need for new approaches CVD. Rare genetic variants lower triglyceride via activation lipolysis CVD suggest treating dyslipidemia. Apolipoprotein C3 (APOC3) angiopoietin-like 3 (ANGPTL3) emerged targets inhibition antibody, antisense, or RNAi approaches. Inhibition either molecule lowers but respectively raises levels. Large clinical trials such agents patients high risk will be required demonstrate efficacy these

Language: Английский

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Metabolic-Dysfunction-Associated Steatotic Liver Disease—Its Pathophysiology, Association with Atherosclerosis and Cardiovascular Disease, and Treatments

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15473 - 15473

Published: Oct. 23, 2023

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a chronic that affects more than quarter of the global population and whose prevalence increasing worldwide due to pandemic obesity. Obesity, impaired glucose metabolism, high blood pressure atherogenic dyslipidemia are risk factors for MASLD. Therefore, insulin resistance may be closely associated with development progression Hepatic entry increased fatty acids released from adipose tissue, increase in acid synthesis reduced oxidation hepatic overproduction triglyceride-rich lipoproteins induce Since also induces atherosclerosis, leading cause death MASLD patients cardiovascular disease. Considering diseases determines prognosis patients, therapeutic interventions should reduce body weight improve coronary factors, addition an improving function. Lifestyle modifications, such as improved diet exercise, surgical interventions, bariatric surgery intragastric balloons, have shown by reducing weight. Sodium cotransporter 2 inhibitors (SGLT2i) glucagon-like peptide-1 receptor agonists (GLP-1RAs) been suppress occurrence diseases. Both SGLT2i GLP-1 reported enzymes, steatosis fibrosis. We recently selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator pemafibrate PPARα multiple anti-atherogenic properties. Here, we consider pathophysiology mechanisms action drugs whether combination therapy could treatments

Language: Английский

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Apolipoprotein B-containing lipoproteins in atherogenesis

Nature Reviews Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

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Lipidomics of familial longevity

Aging Cell, Journal Year: 2013, Volume and Issue: 12(3), P. 426 - 434

Published: March 2, 2013

Middle-aged offspring of nonagenarians, as compared to their spouses (controls), show a favorable lipid metabolism marked by larger LDL particle size in men and lower total triglyceride levels women. To investigate which specific lipids associate with familial longevity, we explore the plasma lipidome measuring 128 species using liquid chromatography coupled mass spectrometry 1526 nonagenarians (59 years ± 6.6) 675 7.4) controls from Leiden Longevity Study. In men, no significant differences were observed between controls. women, however, 19 associated longevity. Female showed higher ether phosphocholine (PC) sphingomyelin (SM) (3.5-8.7%) phosphoethanolamine PE (38:6) long-chain triglycerides (TG) (9.4-12.4%). The association longevity two PC four SM was independent levels. addition, longevity-associated profile characterized ratio monounsaturated (MUFA) over polyunsaturated (PUFA) species, suggesting that female have less prone oxidative stress. Ether identified novel markers females, Several correlated risk hypertension diabetes Study cohort. This sex-specific signature marks may suggest better antioxidant capacity, peroxidation inflammatory precursors, an efficient beta-oxidation function.

Language: Английский

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Diets naturally rich in polyphenols improve fasting and postprandial dyslipidemia and reduce oxidative stress: a randomized controlled trial

American Journal of Clinical Nutrition, Journal Year: 2013, Volume and Issue: 99(3), P. 463 - 471

Published: Dec. 25, 2013

Language: Английский

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