The vicious circle of chronic kidney disease and hypertriglyceridemia: What is first, the hen or the egg?

Chronic kidney disease (CKD) is documented to cause alterations in lipid metabolism, and this was considered a potent driver of increased cardiovascular risk. Among the diverse alteration of lipid traits in CKD, research endeavours have predominantly concentrated on low-density lipoproteins (LDL) in view of the potent pro-atherogenic role of these lipoprotein particles and the demonstration of protective cardiovascular effect of reducing LDL. However, few studies have focused on the metabolism of triglyceride-rich lipoproteins and even fewer on their role in causing kidney damage.

Treatment With Evinacumab Links a New Pathogenic Variant in the LPL Gene to Persistent Chylomicronemia.

Background: Persistent chylomicronemia is caused by lipoprotein lipase deficiency (LPLD) or lack of lipoprotein lipase (LPL) bioavailability. This disorder is characterized by plasma triglyceride (TG) levels above 10 mmol/L, increased acute pancreatitis risk, and features of familial chylomicronemia syndrome (FCS). Evinacumab is an angiopoietin-like protein 3 (ANGPTL3) monoclonal antibody, and its efficacy in decreasing plasma TG levels depends on LPL bioavailability.

An overview of persistent chylomicronemia: much more than meets the eye.

Purpose Of Review: The aim of this review is to provide an overview of severe hypertriglyceridemia presenting in the form of chylomicronemia that persists despite treatment of secondary causes and the use of conventional lipid-lowering treatment.

Recent Findings: Persistent chylomicronemia is a rare syndromic disorder that affects carriers of bi-allelic combinations of pathogenic gene variants impairing lipoprotein lipase (LPL) activity, as well as a significant number of individuals who do not meet this genetic criterion. It is associated with a high risk of acute pancreatitis and other morbidities.

The Hurdle of Access to Emerging Therapies and Potential Solutions in the Management of Dyslipidemias.

This review explores the many barriers to accessing lipid-lowering therapies (LLTs) for the prevention and management of atherosclerotic cardiovascular disease (ASCVD). Geographical, knowledge, and regulatory barriers significantly impede access to LLTs, exacerbating disparities in healthcare infrastructure and affordability. We highlight the importance of policy reforms, including pricing regulations and reimbursement policies, for enhancing affordability and streamlining regulatory processes.

APOC3 siRNA and ASO therapy for dyslipidemia.

Purpose Of Review: The aim of this review is to present the clinical indications of apolipoprotein C-III (apoC3) inhibition in the therapeutic arsenal for the treatment of lipid disorders and associated risks and to compare the most advanced modalities of apoC3 inhibition currently available or in development, specifically APOC3 antisense oligonucleotides (ASO) and small interfering RNA (siRNA).

Recent Findings: ApoC3 inhibition significantly decreases triglyceride levels by mechanisms coupling both lipoprotein lipase (LPL) upregulation and LPL-independent mechanisms. The main apoC3 inhibitors in advanced clinical development are the GalNAc-ASO olezarsen and the GalNAc-siRNA plozasiran.

Inhibition of Angiopoietin-Like Protein 3 or 3/8 Complex and ApoC-III in Severe Hypertriglyceridemia.

Purpose Of Review: The role of the inhibition of ANGPTL3 in severe or refractory hypercholesterolemia is well documented, less in severe hyperTG. This review focuses on the preclinical and clinical development of ApoC-III inhibitors and ANGPTL3, 4, and 3/8 complex inhibitors for the treatment of severe or refractory forms of hypertriglyceridemia to prevent cardiovascular disease or other morbidities.

Recent Findings: APOC3 and ANGPTL3 became targets for drug development following the identification of naturally occurring loss of function variants in families with a favorable lipid profile and low cardiovascular risk.

Post-prandial analysis of fluctuations in the platelet count and platelet function in patients with the familial chylomicronemia syndrome.

Background: The familial chylomicronemia syndrome (FCS) is an ultra rare disease caused by lipoprotein lipase (LPL) deficiency associated with potentially lethal acute pancreatitis risk. Thrombocytopenia (platelet count < 150,000 × 10/L) has been reported in patients with FCS, treated or not with volanesorsen, a second generation APOC3 anti-sense oligonucleotide. Chylomicrons are the lipoproteins delivering fat after a meal and FCS thus has a post-prandial origin.

Correlation between chylomicronemia diagnosis scores and post-heparin lipoprotein lipase activity.

Introduction: Sustained chylomicronemia is a defect in post-prandial triglyceride management characterized by severe hypertriglyceridemia (triglyceride > 10 mmol/L) due to functional or genetic defects in lipoprotein lipase (LPL)-mediated triglyceride-rich lipoprotein lipolysis. Familial chylomicronemia syndrome (FCS) is a rare mendelian form of chylomicronemia caused by loss-of-function variants in LPL or LPL-related genes. Most individuals with chylomicronemia however present multifactorial chylomicronemia (MCS), in which LPL bio-availability and activity are variable.

Methylation profiles of IL33 and CCL26 in bronchial epithelial cells are associated with asthma.

Aim: This study aimed to characterize DNA methylation (DNA-me) in promoter region of IL33, IL1RL1 and CCL26 in asthma and their impacts on transcriptional activity in bronchial epithelial cells (BECs).

Patients & Methods: We performed bis-pyrosequencing, quantitative real-time PCR and sequencing in BECs from ten asthmatic and ten control individuals.

Results: We detected lower DNA-me levels of IL33 and CCL26 in asthmatic than control BECs.