title: Tenascin-C may aggravate left ventricular remodeling and function after myocardial infarction in mice.
abstract: Tenascin-C (TN-C) is an extracellular matrix glycoprotein with high bioactivity. It is expressed at low levels in normal adult heart, but upregulated under pathological conditions, such as myocardial infarction (MI). Recently, we (Ref. 34) reported that MI patients with high serum levels of TN-C have a greater incidence of maladaptive cardiac remodeling and a worse prognosis. We hypothesized that TN-C may aggravate left ventricular remodeling. To examine the effects of TN-C, MI was induced by ligating coronary arteries of TN-C knockout (KO) mice under anesthesia and comparing them with sibling wild-type (WT) mice. In WT+MI mice, TN-C expression was upregulated at day 1, peaked at day 5, downregulated and disappeared by day 28, and the molecule was localized in the border zone between intact myocardium and infarct lesions. The morphometrically determined infarct size and survival rate on day 28 were comparable between the WT+MI and KO+MI groups. Echocardiography and hemodynamic analyses demonstrated left ventricular end-diastolic diameter, myocardial stiffness, and left ventricular end-diastolic pressure to be significantly increased in both WT+MI and KO+MI mice compared with sham-operated mice. However, end-diastolic pressure and dimension and myocardial stiffness of KO+MI were lower than those of the WT+MI mice. Histological examination revealed normal tissue healing, but interstitial fibrosis in the residual myocardium in peri-infarcted areas was significantly less pronounced in KO+MI mice than in WT+MI mice. TN-C may thus accelerate adverse ventricular remodeling, cardiac failure, and fibrosis in the residual myocardium after MI.
authors.affiliation: Dept. of Pathology and Matrix Biology, Mie Univ. Graduate School of Medicine, Tsu, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishioka
authors.forename: Katsuya
authors.initials: K
authors.lastname: Onishi
authors.forename: Naoshi
authors.initials: N
authors.lastname: Shimojo
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nagano
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsusaka
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikeuchi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ide
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Michiaki
authors.initials: M
authors.lastname: Hiroe
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imanaka-Yoshida
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein / Q000502:physiology; D019063:Tenascin / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D019063:Tenascin; D016212:Transforming Growth Factor beta