Increase in ϵ(γ-glutamyl)lysine crosslinks in atherosclerotic aortas

Tissue Transglutaminase and the Progression of Human Renal Scarring

“…In addition, activation of mesangial cells is known to be associated with their transdifferentiation into a myofibroblastic phenotype sharing characteristics with smooth muscle cells and fibroblasts (28). Vascular injury and atherosclerosis associated with smooth muscle cell proliferation has been associated with the upregulation of tTg within these cells (29). Fibroblasts are also known to express tTg.…”

The role of transglutaminase in the rat subtotal nephrectomy model of renal fibrosis.

“…This mechanism may be the case if ECM polymers were formed with a high proportion of bonds resistant to proteolytic degradation, such as ⑀-(␥-glutamyl) lysine bonds formed by transglutaminase (9). Such a mechanism has been postulated to explain the fibrotic process taking place within the walls of atherosclerotic vessels where the cross-linking of matrix proteins is increased (6)(7)(8). The process also is similar to the cross-linking of fibrin by Factor XIII, which makes the crosslinked fibrin much more resistant to plasmin.…”

“…Another factor in the pathogenesis of renal fibrosis may be the resistance of the deposited ECM to breakdown. This resistance has been put forward as a contributing factor in the development of other fibrogenic processes, including lung fibrosis and atherosclerosis (5)(6)(7)(8). Tissue transglutaminase-induced cross-linking of the ECM may underlie its resistance to breakdown.…”

“…Involvement in ECM diseases has also been noted (5), as raised tissue transglutaminase levels have been detected in paraquat-induced pulmonary fibrosis. Since then, transglutaminase has been ascribed roles in atherosclerosis (6)(7)(8), cataract formation (23), and neurofibrillary tangles in Alzheimer's disease (24) and tau-containing polymers (25).…”

Roles of transglutaminases in cardiac and vascular diseases

“…Both factor XIIIa (101) and TG2 (102,103) are present in human atherosclerotic plaque. Furthermore, the transglutaminase-generated isodipeptide epsilon(gamma-glutamyl) lysine is elevated in fibrolipid plaque obtained from diseased aortas of humans and hyperlipidemic rabbits (104). Transglutaminases may have a variety of roles in regulating both the chronic progression of atherosclerosis as well as its acute manifestations.…”