Author/Authors :
Armstrong, Dinani Matoso Filho Medical School - Universidade Federal do Vale do São Francisco (UNIVASF), Petrolina-PE, Brazil , Sikka, Gautam Johns Hopkins University (JHU), Baltimore-MD, USA , Armstrong, Anderson da Costa Medical School - UNIVASF, Petrolina-PE, Brazil , Saad, Karen Ruggeri Medical School - UNIVASF, Petrolina-PE, Brazil , Freitas, William Rodrigues de Medical School - UNIVASF, Petrolina-PE, Brazil , Berkowitz, Dan Ezra Department of Anesthesiology and Critical Care Medicine - JHU, Baltimore-MD, USA , Fagundes, Djalma José Department of Surgery - Universidade Federal de São Paulo (UNIFESP), Brazil , Santhanam, Lakshmi Department of Anesthesiology and Critical Care Medicine - JHU, Baltimore-MD, USA , Taha, Murched Omar Department of Surgery - UNIFESP, Sao Paulo-SP, Brazil
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.
Keywords :
Aging , Transglutaminases , Endothelium-Dependent Relaxing Factors , Mice