Knockdown of transglutaminase-2 prevents early age-induced vascular changes in mice1

Acta Cir Bras. 2018 Nov;33(11):991-999. doi: 10.1590/s0102-865020180110000006.

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.

MeSH terms

  • Age Factors
  • Aging / physiology*
  • Animals
  • Aorta, Thoracic / physiology*
  • Arterial Pressure / physiology
  • Endothelium, Vascular / physiology*
  • GTP-Binding Proteins / physiology*
  • Immunohistochemistry
  • Male
  • Mice, Knockout
  • Protein Glutamine gamma Glutamyltransferase 2
  • Pulse Wave Analysis
  • Transglutaminases / physiology*
  • Vascular Stiffness / physiology
  • Vasodilation / physiology

Substances

  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins