👤 Juliani Juliani

Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary atherosclerosis. Functional aspects of high-density lipoprotein (HDL), including cholesterol transfer capacity, may contribute to cardiovascular risk heterogeneity in FH. To investigate whether cholesterol transfer to HDL and other HDL-related parameters are associated with coronary artery disease (CAD) in patients with heterozygous FH (HeFH). Fifty-three genetically confirmed FH patients (mean age: 49.2 years; 73.6% female) were included. Twenty-seven had plaques, while 26 had no vessel abnormalities as determined by coronary computed tomography angiography. The transfer of both unesterified and esterified cholesterol (UC and EC) to HDL, as well as HDL antioxidant capacity, particle size, and subfractions, plasma concentrations of cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON-1) activity were assessed. Family history of premature CAD (P < .028) and tendinous xanthomas (P = .014) were more frequent in those with plaques. No differences were found in apolipoprotein (apo) B, LDL-C, LDL-C year score, lipoprotein(a), non-HDL-C, apo A-I, HDL-C, HDL subfractions, or triglycerides. Transfer of lipids to HDL and antioxidant capacity did not differ between the groups. LCAT concentrations and PON-1 activity were also similar. In contrast, CETP concentration was higher in those with plaques (P < .008). However, only family history of early CAD (odds ratio [OR]: 4.12, 95% CI, 1.23-13.80, P = .022) and xanthomas (OR: 3.65, 95% CI, 1.06-12.60, P = .040) were independently associated with plaques. Among patients with HeFH, no HDL-related parameter was independently associated with subclinical CAD. Show less

Epithelial and endothelial barriers are essential for tissue homeostasis, protecting the body from environmental insults while regulating selective transport. The integrity of these barriers relies on dynamic intercellular junctions whose composition and organization are constantly remodeled in response to stress and physiological cues. Autophagy and endocytic trafficking are key intracellular pathways that maintain junctional stability and barrier resilience. BECLIN-1 (BECN1), a central regulator of both pathways, coordinates localized membrane dynamics through its interaction with the class III phosphatidylinositol 3-kinase (PtdIns3K) PIK3C3/VPS34. Recent advances reveal that BECN1's dual role in autophagy and endocytic trafficking is crucial for maintaining barriers in diverse tissues, including the gut, skin, and blood-brain barrier. Conversely, BECN1 dysfunction can compromise junctional integrity, driving inflammatory and degenerative diseases. This review summarizes the emerging evidence linking BECN1 to membrane trafficking, stress adaptation, and immune regulation across barrier tissues, highlighting its potential as a therapeutic target for barrier-associated diseases. Show less