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

• Main Author: Armstrong,Dinani Matoso Filho
• Publication Date: 2018
• Other Authors: Sikka,Gautam, Armstrong,Anderson da Costa, Saad,Karen Ruggeri, Freitas,William Rodrigues de, Berkowitz,Dan Ezra, Fagundes,Djalma José, Santhanam,Lakshmi, Taha,Murched Omar
• Format: Article
• Language: eng
• Source: Acta Cirúrgica Brasileira (Online)
• Download full: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502018001100991
• topic: Aging; Transglutaminases; Endothelium-Dependent Relaxing Factors; Mice

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.