Dynamic Expression of Tenascin-C After Myocardial Ischemia and Reperfusion: Assessment by ¹²⁵I-Anti–Tenascin-C Antibody Imaging

Abstract

Tenascin-C, an extracellular matrix glycoprotein, appears only in the early stages of embryonic development. It is not normally expressed in the adult heart but does reappear transiently in distinct areas in association with active tissue remodeling. The aim of this study was to explore serial changes in the expression of tenascin-C after myocardial ischemia and reperfusion, using 125 I-labeled anti-tenascin-C antibody ( 125 I-TNC-Ab) in a rat model of acute ischemia and reperfusion. Methods: The left coronary artery was occluded for 20 or 30 min, followed by reperfusion for 1, 3, or 7 d in rats with 20 min of ischemia and for 1, 3, 7, 14, or 28 d in rats with 30 min of ischemia. At the time of the study, 125 I-TNC-Ab (1.0-2.5 MBq) was injected. Three to 5 h later, to verify the area at risk, 99m Tc-methoxyisobutylisonitrile (100-200 MBq) was injected intravenously just after the left coronary artery reocclusion and the rats were sacrificed 1 min later. Dual-tracer autoradiography was performed to assess 125 I-TNC-Ab uptake and the area at risk. Results: In rats with 20 min of ischemia, 125 I-TNC-Ab uptake peaked at 3 d after reperfusion, followed by faint uptake after 7 d (uptake ratios at 1, 3, and 7 d after reperfusion were 1.81 6 0.53, 2.46 6 0.79, and 1.23 6 0.17, respectively [P , 0.05 vs. 3 d]). In rats with 30 min of ischemia, uptake was high at 1 and 3 d after reperfusion (2.99 6 0.90 and 2.71 6 0.80, respectively), decreased at 7 and 14 d (1.94 6 0.23 and 2.06 6 0.37, respectively), and was weak at 28 d (1.47 6 0.27, P , 0.005 vs. 1 d, P , 0.05 vs. 3 d). Conclusion: These data indicate that 125 I-TNC-Ab imaging may be a way to monitor myocardial injury and its repair process after ischemia and reperfusion by visualizing tenascin-C expression.

Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

“…For instance, it is dynamically expressed following hepatic or myocardial ischemia/reperfusion injury424344. Dysregulation of this glycoprotein was also monitored after cerebral ischemia4546.…”

Comparative mRNA and MicroRNA Profiling during Acute Myocardial Infarction Induced by Coronary Occlusion and Ablation Radio-Frequency Currents

“…We found an increased tenascin (TNC) mRNA expression in both occlusion and ablation. Tenascin is sparsely detected in the normal adult myocardium, but reappears when the heart remodels its structure in response to pathologic insults, such as acute MI (Willems et al, 1996; Imanaka-Yoshida et al, 2001; Sato et al, 2006; Odaka et al, 2008), myocarditis (Imanaka-Yoshida et al, 2002; Sato et al, 2002; Morimoto et al, 2005), hibernation (Frangogiannis et al, 2002), ischemia-reperfusion (Taki et al, 2010), hypertensive cardiac fibrosis (Nishioka et al, 2007), chronic cardiac rejection (Franz et al, 2010), and some cases of dilated cardiomyopathy (DCM) (Tamura et al, 1996; Tsukada et al, 2009) closely associated with inflammation. Several studies suggest that TNC could help tissue reconstruction of the edge of the residual myocardium as a de-adhesion protein.…”

Molecular Imaging of the Cardiac Extracellular Matrix

“…Uptake of antitenascin C monocolonal antibody fragment labeled with 125 I has been evaluated in rat MI models at multiple time points. Tracer uptake in the 20-minute ischemia model peaked at day 3 and declined over time with faint uptake seen at day 7 74 and suggested that probes such as those directed against tenascin may be used to monitor cardiac repair process, the extent of which depends on the severity of tissue damage. To reduce half-life and increase resolution, 111 In-single-chain antitenascin C fragment was produced, and increased uptake in the infarct was demonstrated.…”