Apolipoprotein B-containing lipoproteins in atherogenesis

Nature Reviews Cardiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Язык: Английский

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Lipoprotein(a): from Causality to Treatment

Current Atherosclerosis Reports, Год журнала: 2024, Номер 26(3), С. 75 - 82

Опубликована: Янв. 22, 2024

Язык: Английский

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Hypercholesterolemia and inflammation—Cooperative cardiovascular risk factors

European Journal of Clinical Investigation, Год журнала: 2024, Номер unknown

Опубликована: Окт. 6, 2024

Abstract Background Maintaining low concentrations of plasma low‐density lipoprotein cholesterol (LDLc) over time decreases the number LDL particles trapped within artery wall, slows progression atherosclerosis and delays age at which mature atherosclerotic plaques develop. This substantially reduces lifetime risk cardiovascular disease (ASCVD) events. In this context, plaque development vulnerability result not only from lipid accumulation but also inflammation. Results Changes in composition immune cells, including macrophages, dendritic T B mast cells neutrophils, along with altered cytokine chemokine release, disrupt equilibrium between inflammation anti‐inflammatory mechanisms sites. Considering that it is a competition LDLc inflammation, instead they are partners crime, present narrative review aims to give an overview main inflammatory molecular pathways linked raised describe impact lipid‐lowering approaches on burden. Although remarkable changes driven by most recent lowering combinations, relative reduction C‐reactive protein appears be independent magnitude lowering. Conclusion Identifying clinical biomarkers (e.g. interleukin‐6) possible targets for therapy holds promise monitoring reducing ASCVD burden suitable patients.

Язык: Английский

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Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Where Do We Stand?

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3537 - 3537

Опубликована: Март 21, 2024

Lipoprotein(a) [Lp(a)] consists of a low-density lipoprotein-like molecule and an apolipoprotein(a) [apo(a)] particle. Lp(a) has been suggested to be independent risk factor atherosclerotic cardiovascular disease (ASCVD). plasma levels are considered 70–90% genetically determined through the codominant expression LPA gene. Therefore, almost stable during individual’s lifetime. This lifelong stability, together with difficulties in measuring standardized manner, may account for scarcity available drugs targeting Lp(a). In this review, we synopsize latest data regarding structure, metabolism, factors affecting circulating Lp(a), as well laboratory determination measurement its role pathogenesis ASCVD thrombosis, potential use various therapeutic agents particular, discuss novel agents, such antisense oligonucleotides (ASOs) small interfering RNAs (siRNAs) that currently being developed target The promising muvalaplin, oral inhibitor formation, is then further analyzed.

Язык: Английский

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Updates in Small Interfering RNA for the Treatment of Dyslipidemias

Current Atherosclerosis Reports, Год журнала: 2023, Номер 25(11), С. 805 - 817

Опубликована: Окт. 4, 2023

Abstract Purpose of Review Atherosclerotic cardiovascular disease (ASCVD) is still the leading cause death worldwide. Despite excellent pharmacological approaches, clinical registries consistently show that many people with dyslipidemia do not achieve optimal management, and them are treated low-intensity lipid-lowering therapies. Beyond well-known association between low-density lipoprotein cholesterol (LDL-C) prevention, atherogenicity lipoprotein(a) impact triglyceride (TG)-rich lipoproteins cannot be overlooked. Within this landscape, use RNA-based therapies can help treatment difficult to target lipid disorders. Recent Findings The safety efficacy LDL-C lowering siRNA inclisiran has been documented in open-label ORION-3 trial, a follow-up 4 years. While outcome trial pending, pooled analysis ORION-9, ORION-10, ORION-11 shown potential reduce composite major adverse events. Concerning lipoprotein(a), data OCEAN(a)-DOSE olpasiran dose-dependent drop levels an pharmacodynamic profile when administered every 12 weeks. TG lowering, although ARO-APOC3 ARO-ANG3 effective lower apolipoprotein(apo)C-III angiopoietin-like 3 (ANGPTL3) levels, these drugs their infancy. Summary In era moving toward personalized risk represents blossoming armamentarium tackle dyslipidaemias for ASCVD reduction.

Язык: Английский

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Closing the gaps in patient management of dyslipidemia: stepping into cardiovascular precision diagnostics with apolipoprotein profiling

Clinical Proteomics, Год журнала: 2024, Номер 21(1)

Опубликована: Март 1, 2024

In persons with dyslipidemia, a high residual risk of cardiovascular disease remains despite lipid lowering therapy. Current prediction mainly focuses on low-density lipoprotein cholesterol (LDL-c) levels, neglecting other contributing factors. Moreover, the efficacy LDL-c by statins resulting in reduced is only partially effective. Secondly, from metrological viewpoint falls short as reliable measurand. Both direct and calculated tests produce inaccurate test results at low end under aggressive As underperform both clinically metrologically, there an urging need for molecularly defined biomarkers. Over years, apolipoproteins have emerged promising biomarkers context they are functional workhorses metabolism. Among these, apolipoprotein B (ApoB), present all atherogenic particles, has demonstrated to outperform LDL-c. Other apolipoproteins, such Apo(a) - characteristic emerging factor lipoprotein(a) -, ApoC-III inhibitor triglyceride-rich clearance attracted attention well. To support personalized medicine, we move markers, like apolipoproteins. Molecularly diagnosis targeted therapy require measured This review provides summary scientific validity (patho)physiological role nine serum Apo(a), ApoB, ApoC-I, ApoC-II, ApoC-III, ApoE its phenotypes, ApoA-I, ApoA-II, ApoA-IV, metabolism, their association disease, potential markers when multiplex panel.

Язык: Английский

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Comprehensive evaluation of siRNA therapeutics on Lp(a): A network meta‐analysis

Diabetes Obesity and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

To evaluate the efficacy and safety of siRNA drugs that lower Lp(a) in patients with dyslipidaemia. A network meta-analysis systematic review were conducted to compare targeting Lp(a), based on relevant randomized controlled trials (RCTs). comprehensive search was performed PubMed, Embase, Web Science Cochrane Library (up October 24, 2024). RCTs an intervention duration at least 12 weeks included. Eligible studies compared reduce including both Lp(a)-targeted non-targeted agents, placebo or other Lp(a). The primary outcomes percentage reduction absolute low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo(B)), adverse events serious events, injection-site reactions. risk bias assessed using Risk Bias Tool (ROB2), a random-effects frequentist approach. Confidence effect estimates evaluated In Network Meta-Analysis (CINeMA) framework. total 14 involving 5646 participants particularly Olpasiran, demonstrated strong significantly reducing levels, greatest (mean difference [MD]: -92.06%; 95% CI: -102.43% -81.69%; P-score: 0.98). Olpasiran also showed (MD: -250.70 nmol/L; confidence interval [CI]: -279.89 -221.50; 0.99). Certain non-Lp(a)-targeted such as inclisiran zodasiran, modest reductions by approximately 15%. agents reduced LDL-C more than 20% decreased apo(B) terms safety, most exhibited favourable profiles no significant differences placebo. However, zerlasiran raised concerns regarding reactions when have shown robust effectiveness substantially reductions, moderate improvements concentrations. Non-Lp(a)-targeted demonstrate levels. profile is generally favourable, but may increase incidence

Язык: Английский

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Assessment of Apolipoprotein(a) Isoform Size Using Phenotypic and Genotypic Methods

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(18), С. 13886 - 13886

Опубликована: Сен. 9, 2023

Apolipoprotein(a) (apo(a)) is the protein component that defines lipoprotein(a) (Lp(a)) particles and encoded by LPA gene. The apo(a) extremely heterogeneous in size due to copy number variations kringle-IV type 2 (KIV2) domains. In this review, we aim discuss role of genetics establishing Lp(a) as a risk factor for coronary heart disease (CHD) examining series molecular biology techniques aimed at identifying best strategy possible application clinical research practice, according current gold standard.

Язык: Английский

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Lipoprotein(a) is a highly atherogenic lipoprotein: pathophysiological basis and clinical implications

Current Opinion in Cardiology, Год журнала: 2024, Номер 39(6), С. 503 - 510

Опубликована: Авг. 13, 2024

Purpose of review Lipoprotein(a) has been identified as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. However, reviewed here, there is ongoing debate to the key pathogenic features Lp(a) particles degree atherogenicity relative low-density lipoprotein (LDL). Recent findings Genetic analyses have revealed that on per-particle basis markedly (about six-fold) more atherogenic than LDL. Oxidized phospholipids carried found substantial pro-inflammatory properties triggering pathways may contribute atherogenesis. Whether strength association with ASCVD dependent inflammatory status matter current critical implementing intervention strategies. Contradictory reports continue appear, but most recent studies in large cohorts indicate relationship independent C-reactive protein level. Summary highly viable target significant proportion general population. Better understanding its enhanced important assessment interpreting trials.

Язык: Английский

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What's next for lipoprotein(a)? A national lipid association report from an expert panel discussion

Journal of clinical lipidology, Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

Язык: Английский

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