Serum levels of large tenascin‐C variants, matrix metalloproteinase‐9, and tissue inhibitors of matrix metalloproteinases in concentric versus eccentric left ventricular hypertrophy

Abstract

AimsChronic hypertension may cause left ventricular hypertrophy (LVH). The role of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), and tenascin-C (Tn-C) splice variants in concentric vs. eccentric left ventricular remodelling has not been investigated. Methods and resultsSerum levels of B or C domain containing Tn-C, MMP-9, TIMP-1, -2, and -4 were determined in concentric (left ventricular posterior wall thickness .13 mm and intraventricular septum .13 mm, n ¼ 61) and eccentric (end-diastolic left ventricular diameter .55 mm or end-systolic left ventricular diameter .40 mm, n ¼ 34) LVH by enzyme-linked immunoassays. Levels of B domain containing Tn-C were higher in patients with LVH than in normal volunteers (P ¼ 0.020) and higher in eccentric LVH (EH) compared with concentric LVH (CH) (P ¼ 0.003). A cut-off value of 900 ng/mL might discriminate between these different forms of LVH. Matrix metalloproteinase-9 was higher in patients with LVH than in normal volunteers (P ¼ 0.042), and levels were decreased in EH compared with CH (P ¼ 0.028). Patients with LVH had higher levels of TIMP-1 (P ¼ 0.059), TIMP-2 (P ¼ 0.043), and TIMP-4 (P ¼ 0.163) than normal volunteers, but there were no differences between the LVH groups. ConclusionOur data suggest that myocardial remodelling in LVH is associated with changes in serum levels of MMP-9, TIMP-1, -2, -4, and Tn-C splice variants. In addition, B domain containing Tn-C discriminated EH from CH and might be suggested as a potential diagnostic marker.--

Tenascin-C in cardiovascular remodeling: potential impact for diagnosis, prognosis estimation and targeted therapy

“…Moreover, in particular B domain containing tenascin-C was capable to discriminate between concentric versus eccentric left ventricular hypertrophy with a cut-off value of 900 ng/ml. 7 Also in patients suffering from pulmonary artery hypertension, a relevant expression of tenascin-C could be observed with a correlation to the extent of pulmonary artery alterations. 13,14 In addition, Celik and co-workers reported on significantly elevated tenascin-C serum levels in patients with acute pulmonary embolism and therefore suggested the molecule to be a promising indicator of the disease.…”

“…2 Cardiac ECM reorganization entails the re-occurrence of fetal variants of cell adhesion modulating proteins like fibronectin or tenascin-C. Tenascin-C is known to regulate cell adhesion, inflammation and tissue remodeling not only in cardiovascular diseases 3 Different variants of the molecule are generated by alternative splicing of the premRNA 4,5 These variants show a high expression during critical steps of heart development, are virtually absent in healthy adult hearts and become abundantly re-expressed in the diseased myocardium [6][7][8][9][10] (Fig. 2).…”

Insights into the Activity, Differential Expression, Mutual Regulation, and Functions of Matrix Metalloproteinases and A Disintegrin and Metalloproteinases in Hypertension and Cardiac Disease

“…There have been many studies in humans evaluating the levels of MMPs and ADAMs in the systemic circulation during hypertension and left ventricular hypertrophy, as well as heart failure [84,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130]. A meta-analysis of these studies concluded that elevation of MMP-2 and MMP-9 can be used as plasma biomarkers for cardiovascular remodeling in hypertension [131].…”

Extra cellular matrix remodelling after heterotopic rat heart transplantation: gene expression profiling and involvement of ED-A+ fibronectin, alpha-smooth muscle actin and B+ tenascin-C in chronic cardiac allograft rejection

“…For tenascin-C, A1, B, C or D domain containing variants could be identiWed (Borsi et al 1995;Jones and Jones 2000). These variants are mostly absent in healthy cardiac tissue and show a disease associated re-expression (Gabler et al 1996;Imanaka-Yoshida et al 2001Franz et al 2009Franz et al , 2010a.…”