Tenascin-C in Heart Diseases—The Role of Inflammation

Abstract

Tenascin-C (TNC) is a large extracellular matrix (ECM) glycoprotein and an original member of the matricellular protein family. TNC is transiently expressed in the heart during embryonic development, but is rarely detected in normal adults; however, its expression is strongly up-regulated with inflammation. Although neither TNC-knockout nor -overexpressing mice show a distinct phenotype, disease models using genetically engineered mice combined with in vitro experiments have revealed multiple significant roles for TNC in responses to injury and myocardial repair, particularly in the regulation of inflammation. In most cases, TNC appears to deteriorate adverse ventricular remodeling by aggravating inflammation/fibrosis. Furthermore, accumulating clinical evidence has shown that high TNC levels predict adverse ventricular remodeling and a poor prognosis in patients with various heart diseases. Since the importance of inflammation has attracted attention in the pathophysiology of heart diseases, this review will focus on the roles of TNC in various types of inflammatory reactions, such as myocardial infarction, hypertensive fibrosis, myocarditis caused by viral infection or autoimmunity, and dilated cardiomyopathy. The utility of TNC as a biomarker for the stratification of myocardial disease conditions and the selection of appropriate therapies will also be discussed from a clinical viewpoint.

Assessment of Right Ventricular Function, Blood Lactate Levels, and Serum Peptidomics Profiles Associated With Mitral Valve Disease in Dogs

“…The previous study reported the proteome expression in heart failure patients associated with the inflammation response and oxidative stress ( 19 , 22 ), similar to our present study. The inflammation network response to mitral degeneration included the presentation of mitogen-activated protein 3 kinases (MAP3K), kallikrein related peptide (KLK), and tenascin C (TNC).…”

“…Many studies reported that the use of protein infusions such as kallikrein could improve cardiac function and reduce cardiomyocyte apoptosis and reduce inflammatory cell accumulation in the heart after myocardial ischemia ( 20 , 21 ). Tenascin-C (TN-C) was also another peptide found in the serum of heart failure patients and suggested using it to predict ventricular remodeling and poor prognosis ( 22 ). The proteomic network assessment might be allowed in the evaluation of therapeutic targets for valvular heart diseases.…”

The Pathogenesis of Cardiac Fibrosis: A Review of Recent Progress

“…In the progression of reactive fibrosis, ‘low-grade (smoldering) chronic inflammation’, mediated by macrophages around the perivascular spaces, might be involved [ 12 , 13 , 14 ]. These patterns usually coexist in most HF patients [ 15 , 16 ], thus it is practically difficult to distinguish between reactive and replacement fibrosis caused by small infarct lesions with low-flow ischemia in the advanced stages of myocardial diseases [ 6 , 7 ].…”

“…αSMA is the most commonly used marker for activated fibroblasts. Tenascin-C (TN-C) is highly expressed in activated CFs and is a potential marker for confirming their phenotype [ 6 , 7 ]. Although these are still under investigation, recent single-cell analyses have revealed several candidate markers that are expressed in cardiac valve interstitial fibroblasts, including wif1 and the cartilage oligomeric matrix protein (COMP) [ 70 ].…”

“…However, pathological cardiac remodeling in excessive and continuous tissue damage with subsequent ECM deposition results in distorted organ architecture and significantly impacts cardiac function [ 2 , 4 ]. Collectively, heart diseases, such as myocardial infarction (MI), cardiac hypertrophy due to pressure or volume overload, diabetic cardiomyopathy, and dilated cardiomyopathy (DCM) [ 2 , 5 , 6 , 7 ] are involved in cardiac fibrosis progression. Although fibrosis has pathophysiological importance in cardiovascular disease development, the development and molecular mechanisms of cardiac fibrosis still require investigation.…”