BMP10 functions independently from BMP9 for the development of a proper arteriovenous network

We examined whether globalBmp10-inducible knockout (iKO) mice develop AVMs at neonatal and adult stages in comparison with control,Bmp9-KO, andBmp9/10-double KO (dKO) mice.Bmp10-iKO andBmp9/10-dKO mice showed AVMs in developing retina, postnatal brain, and adult wounded skin, whileBmp9-KO did not display any noticeable vascular defects.Bmp10 deficiency resulted in increased proliferation and size of endothelial cells in AVM vessels. The impaired neurovascular integrity in the brain and retina ofBmp10-iKO andBmp9/10-dKO mice was detected.Bmp9/10-dKO mice exhibited the lethality and vascular malformation similar toBmp10-iKO mice, but their phenotypes were more pronounced. Administration of BMP10 protein, but not BMP9 protein, prevented retinal AVM inBmp9/10-dKO and endothelial-specificEng-iKO mice. These data indicate that BMP10 is indispensable for the development of a proper arteriovenous network, whereas BMP9 has limited compensatory functions for the loss of BMP10. We suggest that BMP10 is the most relevant physiological ligand of the ENG-ALK1 signaling pathway pertinent to HHT pathogenesis.
Source: Angiogenesis - Category: Molecular Biology Source Type: research