Platelet endothelial cell adhesion molecule 1 deficiency misguides venous thrombus resolution.

Abstract:

: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(-/-) 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.

journal_name

Blood

journal_title

Blood

authors

Kellermair J,Redwan B,Alias S,Jabkowski J,Panzenboeck A,Kellermair L,Winter MP,Weltermann A,Lang IM

doi

10.1182/blood-2013-04-499558

subject

Has Abstract

pub_date

2013-11-07 00:00:00

pages

3376-84

issue

19

eissn

0006-4971

issn

1528-0020

pii

blood-2013-04-499558

journal_volume

122

pub_type

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