Arterial Vimentin Is a Transglutaminase Substrate: A Link between Vasomotor Activity and Remodeling?

Abstract

Background/Aims: The transglutaminases (TG2 and factor XIIIa) may contribute to the stability of arteries by cross-linking a variety of substrates, including extracellular matrix proteins and protease inhibitors. The preferred substrates have never been determined, however. Methods: We used an amine donor, 5-biotinamidopentylamine, that is covalently linked to acceptor glutamine residues, to determine transglutaminase substrates in carotid endarterectomy tissue. Results: The incorporation of 5-biotinamidopentylamine was calcium dependent, resulting in the labeling of several proteins that were detected by streptavidin-peroxidase and purified over a monomeric avidin affinity column. A major band of 42 kDa that was eluted from the column was sequenced along with 2 additional bands (80 and 65 kDa), revealing an internal fragment of vimentin, transferrin and albumin, respectively. Vimentin dimers were detected in 5 out of 5 carotid plaque homogenates. Conclusions: Vimentin is a major arterial substrate for transglutaminases. It has previously been shown that TG2 activity and vimentin contribute to vasomotor activity of arteries. Furthermore, transglutaminases (both TG2 and factor XIIIa), as well as vimentin, regulate structural alterations (inward remodeling) that occur in response to low flow states. Transglutaminase-mediated vimentin dimerization produces a novel unifying pathway by which vasodilatory and remodeling responses may be regulated.

Transglutaminases in Vascular Biology: Relevance for Vascular Remodeling and Atherosclerosis

“…Indeed, we observed complete dilatation upon inhibition of Tgase activity in isolated coronary arteries [12]. Others identified vimentin as a major substrate for type 2 Tgase in vascular tissue, and suggested that vimentin links Tgases to vasomotor activity and remodeling [60]. …”

A Combined Proteomic and Transcriptomic Approach Shows Diverging Molecular Mechanisms in Thoracic Aortic Aneurysm Development in Patients with Tricuspid- And Bicuspid Aortic Valve

“…Previous data have indicated differences in TGF␤ signaling pathway between BAV and TAV patients (4,26). Furthermore, vimentin (VIM), one of the components of intermediate filament, is a major substrate for transglutaminases (27). Hence, medial degeneration in TAV patients may be the result of vimentin crosslinking by TGM2, as has been proposed for arterial remodeling (27).…”

“…Furthermore, vimentin (VIM), one of the components of intermediate filament, is a major substrate for transglutaminases (27). Hence, medial degeneration in TAV patients may be the result of vimentin crosslinking by TGM2, as has been proposed for arterial remodeling (27). Moreover, most of the proteins specifically associated with dilatation in TAV i.e.…”

The role of Lamin A in cytoskeleton organization in colorectal cancer cells

“…TG2 is thought to play a role in cytoskeleton organisation, since β-actin, α-actinin, tubulin, cofilin and vimentin are all TG2 substrates. [28][29][30][31] Three protein chaperones, B23, Hsp60 and mortalin (heat shock 70 kDa protein 9) were all under-represented in the cytoskeleton fraction of SW480/lamA cells. All three proteins have been implicated in cancer progression [32][33][34] and all three bind to cytoskeleton proteins and influence cytoskeleton dynamics and organisation.…”