Effect of tissue transglutaminase (TG2) on cardiac and vascular function in young TG2 knockout mice

Background. Structural changes of the arterial wall are associated with increased arterial stiffness and hypertension. Tissue transglutaminase (TG2), an enzyme ubiquitously expressed in the vasculature, forms stable crosslinks between extracellular matrix proteins, including collagen. Due to its role in small artery remodelling, calcification and atherosclerosis, TG2 has been implicated in cardiovascular disease. The aim of this study was to compare parameters of cardiac and vascular function between TG2 knockout mice and wild-type littermates. Methods. Male TG2^-/- (n=4) and TG2^+/+ (n=4) mice, aged 16 weeks, were anaesthetized with isoflurane. Aortic pressure was recorded with a 1.2F high fidelity sensor via the left carotid artery. Mean and pulse pressure and augmentation index were determined from the pressure signal; baroreflex sensitivity computed from directional changes of systolic pressure and interbeat interval (ECG), and aortic pulse transit time from the R wave to foot of the aortic pulse. Ventricular weight was expressed as percentage of total body weight. Results. TG2^-/- mice showed significant differences only in relative ventricular weight compared to wild-type controls. Conclusion. Although findings suggest a tendency for increased ventricular mass, TG2 does not influence other baseline cardiovascular parameters in young healthy mice. This is consistent with TG2 activity, which is modulated by Ca²⁺ and endothelial nitric oxide, being generally increased in inflammation and ageing. However, this study lays the ground work for future experiments in which inflammation or endothelial dysfunction will be induced, whereby TG2^-/- mice would be expected to be protected from associated increase in vascular dysfunction and stiffness.