Published online before print July 22, 2002, doi: 10.1161/01.CIR.0000027104.33206.C8
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:993.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Prevention of Diabetes-Induced Microangiopathy by Human Tissue Kallikrein Gene Transfer
From Cardiovascular Medicine and Gene Therapy Section, National Laboratory of the National Institute of Biostructures and Biosystems (INBB) (C.E., M.B.S., A.P., T.S., A.F.M., A.S., P.M.), Osilo, Italy; Internal Medicine (P.M.) and Physiological, Biochemical and Cellular Sciences (A.S., L.S.), University of Sassari, Sassari, Italy; and Department of Biochemistry and Molecular Biology (J.C, L.C.), Medical University of South Carolina, Charleston, SC.
Correspondence to Paolo Madeddu, Cardiovascular Medicine and Gene Therapy Section, INBB National Laboratory, Viale S. Antonio, 07033 Osilo (SS), Italy. E-mail madeddu{at}yahoo.com
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.
Key Words: diabetes mellitus • microangiopathy • gene therapy • angiogenesis • apoptosis
This article has been cited by other articles:
 |
|
 |
|
  D. Westermann, T. Walther, K. Savvatis, F. Escher, M. Sobirey, A. Riad, M. Bader, H.-P. Schultheiss, and C. Tschope Gene Deletion of the Kinin Receptor B1 Attenuates Cardiac Inflammation and Fibrosis During the Development of Experimental Diabetic Cardiomyopathy Diabetes, June 1, 2009; 58(6): 1373 - 1381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. A. Stone, C. Richer, C. Emanueli, V. van Weel, P. H.A. Quax, R. Katare, N. Kraenkel, P. Campagnolo, L. S. Barcelos, M. Siragusa, et al. Critical Role of Tissue Kallikrein in Vessel Formation and Maturation: Implications for Therapeutic Revascularization Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 657 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Y. Yao, H. Yin, B. Shen, R. S. Smith Jr, Y. Liu, L. Gao, L. Chao, and J. Chao Tissue kallikrein promotes neovascularization and improves cardiac function by the Akt-glycogen synthase kinase-3{beta} pathway Cardiovasc Res, December 1, 2008; 80(3): 354 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Spinetti, N. Kraenkel, C. Emanueli, and P. Madeddu Diabetes and vessel wall remodelling: from mechanistic insights to regenerative therapies Cardiovasc Res, May 1, 2008; 78(2): 265 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kobayashi, F. A. DeLano, and G. W. Schmid-Schonbein Oxidative Stress Promotes Endothelial Cell Apoptosis and Loss of Microvessels in the Spontaneously Hypertensive Rats Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2114 - 2121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Y. Kostrominova, D. E. Dow, R. G. Dennis, R. A. Miller, and J. A. Faulkner Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles Physiol Genomics, July 14, 2005; 22(2): 227 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chao and L. Chao Kallikrein-kinin in stroke, cardiovascular and renal disease Exp Physiol, May 1, 2005; 90(3): 291 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Madeddu Therapeutic angiogenesis and vasculogenesis for tissue regeneration Exp Physiol, May 1, 2005; 90(3): 315 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Emanueli, M. B. Salis, S. Van Linthout, M. Meloni, E. Desortes, J.-S. Silvestre, M. Clergue, C. D. Figueroa, S. Gadau, G. Condorelli, et al. Akt/Protein Kinase B and Endothelial Nitric Oxide Synthase Mediate Muscular Neovascularization Induced by Tissue Kallikrein Gene Transfer Circulation, September 21, 2004; 110(12): 1638 - 1644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Porcu, C. Emanueli, E. Desortes, G. M. Marongiu, F. Piredda, L. Chao, J. Chao, and P. Madeddu Circulating Tissue Kallikrein Levels Correlate With Severity of Carotid Atherosclerosis Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1104 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. TSCHOPE, T. WALTHER, J. KONIGER, F. SPILLMANN, D. WESTERMANN, F. ESCHER, M. PAUSCHINGER, J. B. PESQUERO, M. BADER, H.-P. SCHULTHEISS, et al. Prevention of cardiac fibrosis and left ventricular dysfunction in diabetic cardiomyopathy in rats by transgenic expression of the human tissue kallikrein gene FASEB J, May 1, 2004; 18(7): 828 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Emanueli, G. Graiani, M. B. Salis, S. Gadau, E. Desortes, and P. Madeddu Prophylactic Gene Therapy With Human Tissue Kallikrein Ameliorates Limb Ischemia Recovery in Type 1 Diabetic Mice Diabetes, April 1, 2004; 53(4): 1096 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Frisbee Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H104 - H111. [Abstract] [Full Text] [PDF]
|
|