Transglutaminase activity is decreased in large arteries from hypertensive rats compared with normotensive controls

Abstract

Watts SW. Transglutaminase activity is decreased in large arteries from hypertensive rats compared with normotensive controls. Am J Physiol Heart Circ Physiol 308: H592-H602, 2015. First published January 16, 2015; doi:10.1152/ajpheart.00402.2014 catalyze the formation of covalent crosslinks between glutamine residues and amine groups. This crosslinking activity has been implicated in arterial remodeling. Because hypertension is characterized by arterial remodeling, we hypothesized that TG activity, expression, and functionality would be increased in the aorta, but not in the vena cava (which does not undergo remodeling), from hypertensive rats relative to normotensive rats. Spontaneously hypertensive stroke-prone rats (SHRSP) and DOCA-salt rats as well as their respective normotensive Wistar-Kyoto or SpragueDawley counterparts were used. Immunohistochemistry and Western blot analysis measured the presence and expression of TG1 and TG2, in situ activity assays quantified active TGs, and isometric contractility was used to measure TG functionality. Contrary to our hypothesis, the activity (52% DOCA-salt vs. control rats and 56% SHRSP vs. control rats, P Ͻ 0.05), expression (TG1: 54% DOCA-salt vs. control rats, P Ͼ 0.05, and TG2: 77% DOCA-salt vs. control rats, P Ͻ 0.05), and functionality of TG1 and TG2 were decreased in the aorta, but not in the vena cava, from hypertensive rats. Mass spectrometry identified proteins uniquely amidated by TGs in the aorta that play roles in cytoskeletal regulation, redox regulation, and DNA/RNA/protein synthesis and regulation and in the vena cava that play roles in cytoskeletal regulation, coagulation regulation, and cell metabolism. Consistent with the idea that growing cells lose TG2 expression, vascular smooth muscle cells placed in culture lost TG2 expression. We conclude that the expression, activity, and functionality of TG1 and TG2 are decreased in the aorta, but not in the vena cava, from hypertensive rats compared with control rats. transglutaminase; hypertension; aorta; vena cava; arterial remodeling TRANSGLUTAMINASES (TGs) are a family of Ca 2ϩ -dependent enzymes that are best known for catalyzing the formation of a covalent bond between an amine group and the ␥-carboxamide group of a glutamine residue (8). The amine can come from a variety of sources, including polyamines (7), monoamines such as serotonin [5-hydroxytryptamine (5-HT)] (19), or peptide-or protein-bound lysines (14). TG1, TG2, TG4, and factor XIII have been identified in the vasculature, but only TG1, TG2, and TG4 are expressed by vascular smooth muscle cells (VSMCs) (4, 10). The cross-linking activity of TGs is of particular interest in blood vessels because such activity has the ability to stabilize cytoskeletal and extracellular matrix proteins (4), processes involved in vessel remodeling. TG1 helps maintain endothelial barrier function (4), and small artery inward remodeling in rat in response to low blood flow is dependent on the activity of TG2 (1). Additionally, TG activity is required for multip...

Tissue Transglutaminase Modulates Vascular Stiffness and Function Through Crosslinking‐Dependent and Crosslinking‐Independent Functions

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“…51 TG2 protein expression is lost in the SMCs of hypertensive rats (corresponding to proliferative SMC phenotype). 52 These findings are supportive of our current results. However, in response to stress or growth factors, cell-surface TG2 can promote dedifferentiation and proliferation of SMCs.…”

Cell type specific adhesion to surfaces functionalised by amine plasma polymers

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Vascular Fibrosis in Aging and Hypertension: Molecular Mechanisms and Clinical Implications

“…Recent evidence indicates altered TG2 activity and functionality in large arteries of hypertensive rats. 17 TG2 dysregulation has also been implicated in small-vessel changes and inward remodelling in hypertension. 18 Fundamental to many of the processes underlying ECM reorganization and fibrosis in aging and hypertension is activation of MMPs and TIMPs.…”

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