Arthur HM

Doevendans PA

Driessens MH

Feijen A

Goumans M-J

Jansen MA

Lebrin F

Mager JJ

Mummery CL

Post S

Snijder RJ

Ten Dijke P

Van Den Driesche S

Van Echteld CJA

Van Laake LW

Westermann CJJ

BACKGROUND - Endoglin, an accessory receptor for transforming growth factor-β in vascular endothelial cells, is essential for angiogenesis during mouse development. Mutations in the human gene cause hereditary hemorrhagic telangiectasia type 1 (HHT1), a disease characterized by vascular malformations that increase with age. Although haploinsufficiency is the underlying cause of the disease, HHT1 individuals show great heterogeneity in age of onset, clinical manifestations, and severity. METHODS AND RESULTS - In situ hybridization and immunohistochemical analysis of mouse and human hearts revealed that endoglin is upregulated in neoangiogenic vessels formed after myocardial infarction. Microvascularity within the infarct zone was strikingly lower in mice with reduced levels of endoglin (Eng) compared with wild-type mice, which resulted in a greater deterioration in cardiac function as measured by magnetic resonance imaging. This did not appear to be because of defects in host inflammatory cell numbers in the infarct zone, which accumulated to a similar extent in wild-type and heterozygous mice. However, defects in vessel formation and heart function in Eng mice were rescued by injection of mononuclear cells from healthy human donors but not by mononuclear cells from HHT1 patients. CONCLUSIONS - These results establish defective vascular repair as a significant component of the origin of HHT1. Because vascular damage or inflammation occurs randomly, it may also explain disease heterogeneity. More generally, the efficiency of vascular repair may vary between individuals because of intrinsic differences in their mononuclear cells. \ua9 2006 American Heart Association, Inc

Newcastle University E-Prints

Endoglin has a crucial role in blood cell-mediated vascular repair

Endoglin has a crucial role in blood cell-mediated vascular repair

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