Protease-activated receptor-2 stimulates angiogenesis and accelerates hemodynamic recovery in a mouse model of hindlimb ischemia

AF Milia, MB Salis, T Stacca, A Pinna… - Circulation …, 2002 - Am Heart Assoc
AF Milia, MB Salis, T Stacca, A Pinna, P Madeddu, M Trevisani, P Geppetti, C Emanueli
Circulation research, 2002Am Heart Assoc
Proteinase-activated receptors (PAR-2) are expressed by the cardiovascular system and
mediate vasodilation, plasma protein extravasation, and endothelial cell proliferation, all
regarded as essential steps for neovascularization. We investigated the angiogenic action of
PAR-2 signaling in vivo. The effect of the PAR-2 activating peptide (PAR-2AP, SLIGRL-NH2)
was assessed in the absence of ischemia, and the therapeutic potential of PAR-2AP and the
PAR-2 agonist trypsin (at 300 and 1.5 nmol IM daily for 21 days, respectively) was also …
Proteinase-activated receptors (PAR-2) are expressed by the cardiovascular system and mediate vasodilation, plasma protein extravasation, and endothelial cell proliferation, all regarded as essential steps for neovascularization. We investigated the angiogenic action of PAR-2 signaling in vivo. The effect of the PAR-2 activating peptide (PAR-2AP, SLIGRL-NH2) was assessed in the absence of ischemia, and the therapeutic potential of PAR-2AP and the PAR-2 agonist trypsin (at 300 and 1.5 nmol IM daily for 21 days, respectively) was also tested in mice subjected to unilateral limb ischemia. PAR-2AP increased capillarity in normoperfused adductor skeletal muscles, whereas neither the vehicle of the PAR2-AP nor the PAR-2 reverse peptide (PAR-2RP, LRGILS-NH2) did produce any effect. In addition, both PAR-2AP and trypsin enhanced reparative angiogenic response to limb ischemia, an effect that was not produced by PAR-2RP or the vehicle of PAR-2 agonists. Potentiation of reparative angiogenesis by PAR-2AP or trypsin resulted in an accelerated hemodynamic recovery and enhanced limb salvage. In conclusions, our study is the first to demonstrate the angiogenic potential of PAR-2 stimulation in vivo. If similar effects occur in humans, PAR-2AP agonists could have some therapeutic potential for the treatment of tissue ischemia.
Am Heart Assoc