Platelet endothelial cell adhesion molecule 1 deficiency misguides venous thrombus resolution

Abstract

Key Points• PECAM-1 deficiency misguides venous thrombus resolution.• PECAM-1 cell surface shedding occurs at the site of venous thrombosis.Platelet endothelial cell adhesion molecule 1 (PECAM-1) is involved in leukocyte migration and angiogenesis, which are key components of venous thrombus resolution. This study investigated the effect of PECAM-1 deficiency on thrombus resolution in FVB/n mice and the extent to which levels of soluble PECAM-1 (sPECAM-1) correlate with delayed thrombus resolution in humans after acute symptomatic deep vein thrombosis (DVT). In a mouse stagnant flow venous thrombosis model Pecam-1 2/2 thrombi were larger, persisted for longer periods of time, and displayed attenuated macrophage invasion and decreased vessel formation in the presence of increased fibrosis. In humans, higher levels of truncated plasma sPECAM-1 possibly cleaved from cell surfaces, were found in patients with delayed thrombus resolution (assessed via duplex-based thrombus scoring) relative to those whose thrombi resolved (median, 25th/75th percentile): 92.5 (87.7/103.4) ng/mL vs 71.5 (51.1/81.0) ng/mL; P < .001. Furthermore, unresolved human deep vein thrombus specimens stained positively with antibodies specific for the extracellular, but not the cytoplasmic domain of PECAM-1, consistent with accumulation of cleaved PECAM-1. Our data suggest a regulatory role of PECAM-1 in venous thrombus resolution and suggest a predictive value of sPECAM-1 for postthrombotic syndrome (PTS) after acute DVT. (Blood. 2013;122(19):3376-3384)

Solitary (juvenile) xanthogranuloma: a comprehensive immunohistochemical study emphasizing recently developed markers of histiocytic lineage

“…CD31 (platelet endothelial cell adhesion molecule-1) is a transmembrane glycoprotein that is expressed by endothelial cells and a variety of hematolymphoid cells [29][30][31]. Although CD31 expression in macrophages is well recognized in the macrophage biology literature [32,33], relatively few reports in the surgical pathology or dermatopathology literature have addressed this finding or the inherent potential for the misdiagnosis of histiocytic processes as endothelial lesions [18,34]. We are aware of only 2 previous series that have evaluated SXG for CD31 expression, one by Tidwell and Googe [26] and another by Nascimento [14].…”

Update on Chronic Thromboembolic Pulmonary Hypertension

“…70 Recently, the sequence of events that promote deep vein thrombosis was analyzed with the use of variations of the murine vena cava ligation model. 3 In the same model, genetic deletion of platelet endothelial cell adhesion molecule 1 4 illustrated the crucial roles of leukocyte migration and angiogenesis 71 in resolution of deep vein thrombosis and resolution of thrombus in CTEPH. Despite all of this evidence, one must bear in mind the limitations of studying thrombosis and thrombus resolution in animals or in in vitro models.…”

“…Those have been set by (1) the International CTEPH Association, which was founded in 2006 as "Association for Research in CTEPH" with the goal to increase awareness, foster worldwide collaboration among centers, provide a platform for surgical centers, establish the European and International CTEPH registries, facilitate training of emerging centers, and advance basic and translational research in CTEPH; (2) the 2008, 2011, and 2014 International Scientific and Educational Workshops in CTEPH in Vienna, Austria, Cambridge, UK, and Paris, France bringing together international groups of experts in the field of CTEPH research; (3) modification and refinement of surgical techniques in addressing patients with distal disease, thereby improving outcomes and availability of the procedure for patients who may have been considered nonoperable in the past; (4) the Fifth World Symposium on Pulmonary Hypertension in Nice, France, in February 2013; and (5) the approval of the first drug for the treatment of nonoperable CTEPH and persistent/ recurrent PH after PEA in October 2013. Scientific advances have been spearheaded by deeper insights into the biology of thrombus resolution, 3,4 the characterization of the European CTEPH population, 5 the definition of the "CTEPH team," 6 the proof of safety of deep hypothermic circulatory arrest during PEA, 7,8 and the technical refinement of balloon pulmonary angioplasty (BPA) 9 by Japanese investigators. [10][11][12][13] It is to be expected that these milestones will lead to a better understanding of CTEPH.…”

Ly6Clow and Not Ly6Chigh Macrophages Accumulate First in the Heart in a Model of Murine Pressure-Overload

“…Here, the expression of the integrin heterodimer CD11b, also known as Mac-1, on the surface of monocytes and granulocytes directly influences cell adhesion and transendothelial migration as it interacts with the intercellular adhesion molecule 1 (ICAM-1) on endothelial cells [16]–[18]. Moreover, platelet/endothelial-cell adhesion molecule 1 (PECAM1), also known as CD31 has been reported to be another important junctional molecule, for which leukocytes express ligands, that facilitates cell adhesion and extravasation [19], [20]. In that context, the chemokine receptor CX3CR1, which is also known as fractalkine receptor, contributes to cell recruitment during inflammation through chemotaxis and mediation of adhesion [21]–[23].…”