title: Transglutaminase activity is decreased in large arteries from hypertensive rats compared with normotensive controls.
abstract: Transglutaminases (TGs) catalyze the formation of covalent cross-links between glutamine residues and amine groups. This cross-linking 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 Sprague-Dawley 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 < 0.05), expression (TG1: 54% DOCA-salt vs. control rats, P > 0.05, and TG2: 77% DOCA-salt vs. control rats, P < 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.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan; and peter647@msu.edu.
authors.forename: Humphrey G
authors.initials: HG
authors.lastname: Petersen-Jones
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan; and.
authors.forename: Kyle B
authors.initials: KB
authors.lastname: Johnson
authors.affiliation: Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Hitomi
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan; and.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Tykocki
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan; and.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Thompson
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan; and.
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Watts
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology* / Q000503:physiopathology; D002478:Cells, Cultured; D064791:Desoxycorticosterone Acetate; D004195:Disease Models, Animal; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D009392:Nephrectomy; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D011503:Transglutaminases / Q000378:metabolism*; D066253:Vascular Remodeling; D014661:Vasoconstriction; D014682:Vena Cava, Inferior / Q000201:enzymology
chemical_list: C000717609:Tgm2 protein, rat; D064791:Desoxycorticosterone Acetate; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; C105804:transglutaminase 1; D019204:GTP-Binding Proteins
keywords: aorta; arterial remodeling; hypertension; transglutaminase; vena cava