Fluorescent probes of tissue transglutaminase reveal its association with arterial stiffening.

Tissue transglutaminase (TG2) catalyzes the crosslinking of proteins. TG2 has been implicated in fibrosis and vascular calcification, both of which lead to a common feature of aging known as arterial stiffness. In order to probe the role of TG2 in arterial rigidification, we have prepared a fluorescent irreversible inhibitor as a probe for TG2 activity (RhodB-PGG-K(Acr)-LPF-OH). This probe was synthesized on solid support, characterized kinetically (k(inact) = 0.68 min⁻¹, K(I) = 79 μM), and then used to stain the aorta from rats used as a model of isolated systolic hypertension (ISH). Interestingly, TG2 activity was thus shown to increase over 4 weeks of the hypertension model, corresponding with the previously observed increase in arterial stiffness. These results clearly suggest an association between TG2 and the phenomenon of arterial rigidification.