Prevention of diabetes-induced microangiopathy by human tissue kallikrein gene transfer

Microvascular insufficiency represents a major cause of end-organ failure among diabetics. 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...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2002-08, Vol.106 (8), p.993-999
Main Authors: EMANUELI, Costanza, SALIS, Maria B, PINNA, Alessandra, STACCA, Tiziana, MILIA, Anna F, SPANO, Alessandra, CHAO, Julie, CHAO, Lee, SCIOLA, Luigi, MADEDDU, Paolo
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Associated diseases and complications
Biological and medical sciences
Combined Modality Therapy
Diabetes Mellitus, Experimental - complications
Diabetes. Impaired glucose tolerance
Diabetic Angiopathies - etiology
Diabetic Angiopathies - pathology
Diabetic Angiopathies - prevention & control
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Genetic Therapy
Hindlimb - blood supply
Humans
Hypoglycemic Agents - therapeutic use
Insulin - therapeutic use
Ischemia - etiology
Ischemia - pathology
Ischemia - prevention & control
Kinetics
Male
Medical sciences
Mice
Microcirculation - drug effects
Microcirculation - pathology
Muscle, Skeletal - blood supply
Muscle, Skeletal - chemistry
Muscle, Skeletal - pathology
Nucleotides, Cyclic - analysis
Tissue Kallikreins - genetics
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Summary:Microvascular insufficiency represents a major cause of end-organ failure among diabetics. 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. Our studies indicate that hTK may represent a useful tool for the treatment of microvascular complications in diabetics.
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.0000027104.33206.C8