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Vascular remodeling underlies rebleeding in hemophilic arthropathy
Author(s) -
Bhat Vikas,
Olmer Merissa,
Joshi Shweta,
Durden Donald L.,
Cramer Thomas J.,
Barnes Richard FW,
Ball Scott T.,
Hughes Tudor H.,
Silva Mauricio,
Luck James V.,
Moore Randy E.,
Mosnier Laurent O.,
von Drygalski Annette
Publication year - 2015
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24133
Subject(s) - medicine , hemarthrosis , arthropathy , vascularity , endoglin , pathology , clotting factor , angiogenesis , von willebrand factor , rheumatoid arthritis , osteoarthritis , surgery , platelet , stem cell , alternative medicine , biology , cd34 , genetics
Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII‐deficient mouse. We found soft‐tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft‐tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII‐deficient mice involved pronounced remodeling with expression of α‐Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of α‐SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease. Am. J. Hematol. 90:1027–1035, 2015. © 2015 Wiley Periodicals, Inc.