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

Dinani Matoso Filho Armstrong, Gautam Sikka, Anderson da Costa Armstrong, Karen Ruggeri Saad, William Rodrigues de Freitas, Dan Ezra Berkowitz, Djalma José Fagundes, Lakshmi Santhanam, Murched Omar Taha

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)991-999
Number of pages9
JournalActa cirurgica brasileira
Volume33
Issue number11
DOIs
StatePublished - Nov 1 2018

Keywords

  • Aging
  • Endothelium-dependent relaxing factors
  • Mice
  • Transglutaminases

ASJC Scopus subject areas

  • Surgery

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