Rescue of impaired angiogenesis in spontaneously hypertensive rats by intramuscular human tissue kallikrein gene transfer

Costanza Emanueli, Maria Bonaria Salis, Tiziana Stacca, Leonardo Gaspa, Julie Chao, Lee Chao, Andrea Piana, Paolo Madeddu

Research output: Contribution to journalArticle

Abstract

Angiogenesis represents a compensatory response targeted to preserve the integrity of tissues subjected to ischemia. The aim of the present study was to examine whether reparative angiogenesis is impaired in spontaneously hypertensive rats (SHR), as a function of progression of hypertension. In addition, the potential of gene therapy with human tissue kallikrein (HK) in revascularization was challenged in SHR and normotensive Wistar-Kyoto rats (WKY) that underwent excision of the left femoral artery. Expression of vascular endothelial growth factor and HK was upregulated in ischemic hindlimb of WKY but not of SHR. Capillary density was increased in ischemic adductor muscle of WKY (from 266±20 to 633±73 capillaries/mm2 at 28 days, P2, P=NS), thus compromising perfusion recovery as indicated by reduced plantar blood flow ratio (0.61±0.08 versus 0.92±0.07 in WKY at 28 days, P9 pfu adenovirus containing the HK gene (Ad.CMV-cHK) or the β-galactosidase gene (Ad.CMV-LacZ) was injected intramuscularly at 7 days after the induction of ischemia. Ad.CMV-cHK augmented capillary density and accelerated hemodynamic recovery in both strains, but these effects were more pronounced in SHR (P

Original languageEnglish
Pages (from-to)136-141
Number of pages6
JournalHypertension
Volume38
Issue number1
Publication statusPublished - 2001

Keywords

  • Angiogenesis
  • Genes
  • Ischemia
  • Kallikrein
  • Muscles

ASJC Scopus subject areas

  • Internal Medicine

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    Emanueli, C., Salis, M. B., Stacca, T., Gaspa, L., Chao, J., Chao, L., Piana, A., & Madeddu, P. (2001). Rescue of impaired angiogenesis in spontaneously hypertensive rats by intramuscular human tissue kallikrein gene transfer. Hypertension, 38(1), 136-141.