BACKGROUND: Microvascular insufficiency represents a major cause of end-organ failure among diabetics. METHODS AND RESULTS: In streptozotocin-induced diabetic mice, we evaluated the potential of human tissue kallikrein (hTK) gene as a sole therapy against peripheral microangiopathy. Local delivery of hTK gene halted the progression of microvascular rarefaction in hindlimb skeletal muscle by inhibiting apoptosis, thus ensuring an improved hemodynamic recovery in case of supervening vascular occlusion. The curative action of hTK did not necessitate insulin supplementation. Application of gene therapy at a stage of established microangiopathy stimulated vascular regeneration. CONCLUSIONS: Our studies indicate that hTK may represent a useful tool for the treatment of microvascular complications in diabetics.
BACKGROUND:Microvascular insufficiency represents a major cause of end-organ failure among diabetics. METHODS AND RESULTS: In streptozotocin-induced diabeticmice, we evaluated the potential of humantissue kallikrein (hTK) gene as a sole therapy against peripheral microangiopathy. Local delivery of hTK gene halted the progression of microvascular rarefaction in hindlimb skeletal muscle by inhibiting apoptosis, thus ensuring an improved hemodynamic recovery in case of supervening vascular occlusion. The curative action of hTK did not necessitate insulin supplementation. Application of gene therapy at a stage of established microangiopathy stimulated vascular regeneration. CONCLUSIONS: Our studies indicate that hTK may represent a useful tool for the treatment of microvascular complications in diabetics.
Authors: Andrea Caporali; Elisabetta Pani; Anton J G Horrevoets; Nicolle Kraenkel; Atsuhiko Oikawa; Graciela B Sala-Newby; Marco Meloni; Brunella Cristofaro; Gallia Graiani; Aurelie S Leroyer; Chantal M Boulanger; Gaia Spinetti; Sung Ok Yoon; Paolo Madeddu; Costanza Emanueli Journal: Circ Res Date: 2008-06-19 Impact factor: 17.367
Authors: Yu-Yu Yao; Hang Yin; Bo Shen; Robert S Smith; Yuying Liu; Lin Gao; Lee Chao; Julie Chao Journal: Cardiovasc Res Date: 2008-08-09 Impact factor: 10.787
Authors: Oliver A Stone; Christine Richer; Costanza Emanueli; Vincent van Weel; Paul H A Quax; Rajesh Katare; Nicolle Kraenkel; Paola Campagnolo; Luciola S Barcelos; Mauro Siragusa; Graciela B Sala-Newby; Danila Baldessari; Marina Mione; Marie P Vincent; Andrew V Benest; Ayman Al Haj Zen; Julien Gonzalez; David O Bates; Francois Alhenc-Gelas; Paolo Madeddu Journal: Arterioscler Thromb Vasc Biol Date: 2009-01-22 Impact factor: 8.311
Authors: G Graiani; C Emanueli; E Desortes; S Van Linthout; A Pinna; C D Figueroa; L Manni; P Madeddu Journal: Diabetologia Date: 2004-05-26 Impact factor: 10.122