👤 Suzan Shochat

Pulmonary artery (PA) dilatation is a common feature of pulmonary hypertension (PH). While lung transplantation (LTx) leads to significant hemodynamic improvements, the effect on PA diameter remains unclear. This study aims to evaluate changes in PA diameter following LTx in patients with preexisting PH and determine whether structural vascular changes regress alongside pulmonary pressure normalization. We retrospectively assessed 18 patients with PH who underwent LTx between 2002 and 2023. Main PA, right PA (RPA), and left PA (LPA) diameters were measured via computed tomography (CT) imaging pre-transplant and annually post-transplant (up to 12 years). Systolic pulmonary arterial pressure (SPAP) was assessed by echocardiography. Despite a significant reduction in SPAP, PA diameter remained largely unchanged (mean pre-LTx: 29.7 mm; post-LTx: 30.0 mm, P=0.670). The aorta diameter increased slightly (P=0.0027), and the PA-to-aorta (PA/Ao) ratio decreased (from 1.08 to 1.00; P=0.027). RPA and LPA showed no significant dimensional changes. Correlation between PA size and SPAP was weak and not significant both pre- and post-LTx (r=0.087 and 0.388, respectively). In contrast to some previous reports suggesting vascular remodeling post-LTx, our findings suggest that PA diameter may remain dilated in some PH patients, even after normalization of pulmonary pressures. This could reflect the presence of structural changes that are less responsive to hemodynamic improvements and warrants a careful interpretation of persistent PA dilation on chest CTs following LTx. Show less

Angiopoietin-like 4 (ANGPTL4) is a secretory protein that can be cleaved to form an N-terminal and a C-terminal protein. Studies performed thus far have linked ANGPTL4 to several cancer-related and metabolic processes. Notably, several point mutations in the C-terminal ANGPTL4 (cANGPTL4) have been reported, although no studies have been performed that ascribed these mutations to cancer-related and metabolic processes. In this study, we compared the characteristics of tumors with and without wild-type (wt) cANGPTL4 and tumors with cANGPTL4 bearing the T266M mutation (T266M cANGPTL4). We found that T266M cANGPTL4 bound to integrin α5β1 with a reduced affinity compared to wt, leading to weaker activation of downstream signaling molecules. The mutant tumors exhibited impaired proliferation, anoikis resistance, and migratory capability and had reduced adenylate energy charge. Further investigations also revealed that cANGPTL4 regulated the expression of Glut2. These findings may explain the differences in the tumor characteristics and energy metabolism observed with the cANGPTL4 T266M mutation compared to tumors without the mutation. Show less

A subdomain of the human leptin receptor encoding part of the extracellular domain (amino acids 428 to 635) was subcloned, expressed in a prokaryotic host, and purified to homogeneity, as evidenced by SDS-PAGE, with over 95% monomeric protein. The purified leptin-binding domain (LBD) exhibited the predicted beta structure, was capable of binding human, ovine, and chicken leptins, and formed a stable 1:1 complex with all mammalian leptins. The binding kinetics, assayed by surface plasmon resonance methodology, showed respective k(on) and k(off) values (mean +/- S.E.) of 1.20 +/- 0.23 x 10(-5) mol(-1) s(-1) and 1.85 +/- 0.30 x 10(-3) s(-1) and a K(d) value of 1.54 x 10(-8) m. Similar results were achieved with conventional binding experiments. LBD blocked leptin-induced, but not interleukin-3-induced, proliferation of BAF/3 cells stably transfected with the long form of human leptin receptor. The modeled LBD structure and the known three-dimensional structure of human leptin were used to construct a model of 1:1 LBD.human leptin complex. Two main residues, Phe-500, located in loop L3, and Tyr-441, located in L1, are suggested to contribute to leptin binding. Show less