Mena and VASP are required for vascular smooth muscle relaxation

Abstract

Enabled/vasodilator stimulated phosphoproteins (Ena/VASP) proteins are important regulators of the cytoskeleton, linking kinase signaling pathways to actin assembly. In mammals, the Ena/VASP family of proteins consists of mammalian enabled (Mena), VASP, and Ena-VASP-like protein (EVL). The proteins are well known targets of cAMP- and cGMP-dependent protein kinases, PKA and PKG, respectively. Given the importance of cyclic nucleotide signaling in mediating vasodilation, we investigated the role of Ena/VASP protein in vascular smooth muscle relaxation. Whereas VASP and Mena were strongly expressed in vascular smooth muscle cells, EVL was undetectable in the arterial wall and EVL-deficiency had no impact on agonist-induced smooth muscle relaxation. VASP deletion impaired the acetylcholine (ACh)- and nitric oxide (NO)-induced relaxation murine mesenteric arteries ex vivo. Similarly, the ACh-induced and NO-dependent relaxation of aorta from 7-month-old but not 3- month-old VASP-/- mice was also reduced. Aortas from animals lacking VASP and expressing only minimal amounts of Mena displayed significantly impaired relaxations in response to NO, cAMP and cGMP stimulation. These results suggest that Mena and VASP play an important role in agonist induced smooth muscle relaxation and functionally compensate for each other.