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

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 I-125-labeled anti-tenascin-C antibody (I-125-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, 125I-TNC-Ab (1.0-2.5 MBq) was injected. Three to 5 h later, to verify the area at risk, 99mTc-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 125I-TNC-Ab uptake and the area at risk. Results: In rats with 20 min of ischemia, 125I-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 +/- 0.53, 2.46 +/- 0.79, and 1.23 +/- 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 +/- 0.90 and 2.71 +/- 0.80, respectively), decreased at 7 and 14 d (1.94 +/- 0.23 and 2.06 +/- 0.37, respectively), and was weak at 28 d (1.47 +/- 0.27, P, 0.005 vs. 1 d, P, 0.05 vs. 3 d). Conclusion: These data indicate that I-125-TNC-Ab imaging may be a way to monitor myocardial injury and its repair process after ischemia and reperfusion by visualizing tenascin-C expression.