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(Circulation. 2002;106:993.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Prevention of Diabetes-Induced Microangiopathy by Human Tissue Kallikrein Gene Transfer

Costanza Emanueli, PhD^*; Maria B. Salis, PharmD^*; Alessandra Pinna, BS; Tiziana Stacca, BS; Anna F. Milia, PharmD; Alessandra Spano, PhD; Julie Chao, PhD; Lee Chao, PhD; Luigi Sciola, BS; Paolo Madeddu, MD

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

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