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

Costanza Emanueli, Maria B. Salis, Alessandra Pinna, Tiziana Stacca, Anna F. Milia, Alessandra Spano, Julie Chao, Lee Chao, Luigi Sciola, Paolo Madeddu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)993-999
Number of pages7
JournalCirculation
Volume106
Issue number8
DOIs
Publication statusPublished - Aug 20 2002

Keywords

  • Angiogenesis
  • Apoptosis
  • Diabetes mellitus
  • Gene therapy
  • Microangiopathy

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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