Objectives: 

Angiogenesis is an essential process for the maintenance and organism recovery. There are many factors that regulate and control this process. The transforming growth factor beta or (TGF-β) is one of them. TGF-β propagates the signal through two types of membrane receptors (type I and type II). ALK1 is a transforming growth factor beta(TGF-β)receptor type I expressed mainly on endothelial cells and involved in vascular remodeling and angiogenesis. ALK1 mutations are associated with hereditary hemorrhagic telangiectasia type 2 (HHT2),a dominantly inherited vascular disorder characterized by multisystemic vascular dysplasia and recurrent hemorrhage. The aim of the present study was to evaluate the effect of ALK1 haploinsufficiency in angiogenesis by using endothelial cells.

Materials: 

We generated primary cultures of mice lung endothelial cells (MLEC) from ALK1 haploinsufficiency (ALK1+/­) mice and its control littermates (ALK1+/+) mice. We analyzed the effects of ALK1 haploinsufficiency on extracellular matrix synthesis by western blot, and cell proliferation by MTT and western blot.

Results: 

ALK1 +/­ MLECs proliferation was increased respect to ALK1+/+ MLECs. Collagen type I synthesis was lower in ALK1 +/­ MLECs than in ALK1+/+ MLECs. These data reveal the role of ALK1 in modulating proliferation and extracellular matrix synthesis in endothelial cells.Our results show the important effect of ALK-1 haploinsufficiecy in the angiogenic process.

Conclusions: 

The main consequence of alterations on these processes is angiogenic disorders. The progression in our understanding on the functional role of ALK1 might have important relevance in the regulation of the angiogenesis processes and it is a key for an advance in diagnostic and clinical treatment.