Fibrin structure in organized thrombotic material removed during pulmonary artery endarterectormy : the effect of vessel calibre

Pulmonary endarterectomy (PEA) is a curative therapeutic approach in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The location-dependent structural differences of thrombotic material found in pulmonary arteries in CTEPH are poorly investigated. We present the case of a 47-year-old woman with antiphospholipid syndrome, diabetes mellitus and abnormal fibrin phenotype, who underwent PEA for CTEPH. Intravascular material removed bilaterally during PEA (from lobar, segmental and sub-segmental arteries) has been studied using light and scanning electron microscopy (SEM). Light microscopy showed tighter fibrous network in the portions of intraluminal thrombotic material facing the vessel wall, which contained collagen and fibrin fibers, and abundant cells. Cells, evaluated by immunostaining, were present in the whole removed material. Tissue factor expression was also observed with the highest values in the portions of intravascular material facing the vessel wall. In the main pulmonary arteries, SEM images revealed thick fibers of fibrous proteins loosly meshed and few erythrocytes and platelets between them (both dysmorphic “wedged” and fresh cells were present). In the fibrotic layers, containing mainly collagen and fibrin, removed from the lobar/segmental pulmonary arteries we found a stepwise increase in fiber density with decreasing vessel calibre, followed by denser fibrous networks composed of thinner fibers. Elastic fibers in the lobar and segmental arteries were aligned along the blood flow vector. These findings demonstrate differences in the structure of endarterectomized PEA material dependent on the vessel calibre and might contribute to understanding of CTEPH pathophysiology

Homocysteinylated Albumin Promotes Increased Monocyte-Endothelial Cell Adhesion and Up-Regulation of MCP1, Hsp60 and ADAM17

RATIONALE:The cardiovascular risk factor homocysteine is mainly bound to proteins in human plasma, and it has been hypothesized that homocysteinylated proteins are important mediators of the toxic effects of hyperhomocysteinemia. It has been recently demonstrated that homocysteinylated proteins are elevated in hemodialysis patients, a high cardiovascular risk population, and that homocysteinylated albumin shows altered properties. OBJECTIVE:Aim of this work was to investigate the effects of homocysteinylated albumin - the circulating form of this amino acid, utilized at the concentration present in uremia - on monocyte adhesion to a human endothelial cell culture monolayer and the relevant molecular changes induced at both cell levels. METHODS AND RESULTS:Treated endothelial cells showed a significant increase in monocyte adhesion. Endothelial cells showed after treatment a significant, specific and time-dependent increase in ICAM1 and VCAM1. Expression profiling and real time PCR, as well as protein analysis, showed an increase in the expression of genes encoding for chemokines/cytokines regulating the adhesion process and mediators of vascular remodeling (ADAM17, MCP1, and Hsp60). The mature form of ADAM17 was also increased as well as Tnf-α released in the cell medium. At monocyte level, treatment induced up-regulation of ICAM1, MCP1 and its receptor CCR2. CONCLUSIONS:Treatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling

Serum Adhesion Molecule Levels as Prognostic Markers in Patients with Early Systemic Sclerosis: A Multicentre, Prospective, Observational Study

Objective: To assess the utility of circulating adhesion molecule levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease. Methods: Ninety-two Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicentre, observational study. Concentrations of intercellular adhesion molecule (ICAM) -1, E-selectin, L-selectin, and P-selectin in serum samples from all patients were measured by enzyme-linked immunosorbent asssay (ELISA). In 39 patients, adhesion molecule levels were measured each year for four years. The ability of baseline adhesion molecule levels to predict subsequent progression and severity in clinical and laboratory features were evaluated statistically. Results: At their first visit, serum levels of ICAM-1, E-selection, P-selectin were significantly elevated and serum L-selectin levels were significantly reduced in patients with SSc compared with healthy controls. Overall, serum ICAM-1 levels at each time point were significantly inversely associated with the %vital capacity (VC) of the same time and subsequent years by univariate analysis. The initial serum ICAM-1 levels were significantly inversely associated with the %VC at the fourth year by multiple regression analysis. The initial serum P-selectin levels were significantly associated with the health assessment questionnaire disability index (HAQ-DI) at the fourth year by multiple regression analysis. Initial adhesion molecule levels were not significantly associated with other clinical features including skin thickness score. Baseline adhesion molecule levels were not significantly associated with subsequent rate of change of clinical parameters. Conclusion: In patients with SSc, serum levels of ICAM-1 and P-selectin may serve as prognostic indicators of respiratory dysfunction and physical disability, respectively. Further longitudinal studies of larger populations are needed to confirm these findings