Knockdown of transglutaminase-2 prevents early age-induced vascular changes in mice

Academic Article

Abstract

  • Purpose: To determine whether the absence of transglutaminase 2 enzyme (TG2) in TG2 knockout mice (TG2 -/- ) protect them against early age-related functional and histological arterial changes. Methods: Pulse wave velocity (PWV) was measured using non-invasive Doppler and mean arterial pressure (MAP) was measured in awake mice using tail-cuff system. Thoracic aortas were excised for evaluation of endothelial dependent vasodilation (EDV) by wire myography, as well as histological analyses. Results: PWV and MAP were similar in TG2 -/- mice to age-matched wild type (WT) control mice. Old WT mice exhibited a markedly attenuated EDV as compared to young WT animals. The TG2 -/- young and old mice had enhanced EDV responses (p<0.01) as compared to WT mice. There was a significant increase in TG2 crosslinks by IHC in WT old group compared to Young, with no stain in the TG2 -/- animals. Optical microscopy examination of Old WT mice aorta showed thinning and fragmentation of elastic laminae. Young WT mice, old and young TG2 -/- mice presented regularly arranged and parallel elastic laminae of the tunica media. Conclusion: The genetic suppression of TG2 delays the age-induced endothelial dysfunction and histological modifications.
  • Authors

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    Digital Object Identifier (doi)

    Author List

  • Armstrong DMF; Sikka G; Armstrong ADC; Saad KR; de Freitas WR; Berkowitz DE; Fagundes DJ; Santhanam L; Taha MO
  • Start Page

  • 991
  • End Page

  • 999
  • Volume

  • 33
  • Issue

  • 11