Prevention of diabetes-induced microangiopathy by human tissue kallikrein gene transfer.
BACKGROUND
Microvascular insufficiency represents a major cause of end-organ failure among diabetics.


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.
Emanueli
Costanza
C
Cardiovascular Medicine and Gene Therapy Section, National Laboratory of the National Institute of Biostructures and Biosystems, Osilo, Italy.
Salis
Maria B
MB
Pinna
Alessandra
A
Stacca
Tiziana
T
Milia
Anna F
AF
Spano
Alessandra
A
Chao
Julie
J
Chao
Lee
L
Sciola
Luigi
L
Madeddu
Paolo
P
D000818:Animals; D017209:Apoptosis; D003131:Combined Modality Therapy; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015316:Genetic Therapy; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007511:Ischemia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007700:Kinetics; D008297:Male; D051379:Mice; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000737:chemistry / Q000473:pathology; D009712:Nucleotides, Cyclic / Q000032:analysis; D020840:Tissue Kallikreins / Q000235:genetics*
D007004:Hypoglycemic Agents; D007328:Insulin; D009712:Nucleotides, Cyclic; D020840:Tissue Kallikreins