Journal article

Publication year: 2017

Journal: Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease

Volume number: 6

Issue number: 6

ISSN: 2047-9980

Open access status: Gold

DOI Link: https://doi.org/10.1161/JAHA.116.004541

Publisher: Wiley

Abstract: 

Background--Following myocardial infarction (MI), peri-infarct myocardial edema formation further impairs cardiac function. Extracellular RNA (eRNA) released from injured cells strongly increases vascular permeability. This study aimed to assess the role of eRNA in MI-induced cardiac edema formation, infarct size, cardiac function, and survival after acute MI and to evaluate the therapeutic potential of ribonuclease 1 (RNase-1) treatment as an eRNA-degrading intervention.

Methods and Results--C57BL/6J mice were subjected to MI by permanent ligation of the left anterior descending coronary artery. Plasma eRNA levels were significantly increased compared with those in controls starting from 30 minutes after ligation. Systemic application of RNase-1, but not DNase, significantly reduced myocardial edema formation 24 hours after ligation compared with controls. Consequently, eRNA degradation by RNase-1 significantly improved the perfusion of collateral arteries in the border zone of the infarcted myocardium 24 hours after ligation of the left anterior descending coronary artery, as detected by micro-computed tomography imaging. Although there was no significant difference in the area at risk, the area of vital myocardium was markedly larger in mice treated with RNase-1 compared with controls, as detected by Evans blue and 2,3,5-triphenylte-trazolium chloride staining. The increase in viable myocardium was associated with significantly preserved left ventricular function, as assessed by echocardiography. Moreover, RNase-1 significantly improved 8-week survival following MI.

Conclusions--eRNA is an unrecognized permeability factor in vivo, associated with myocardial edema formation after acute MI. RNase-1 counteracts eRNA-induced edema formation and preserves perfusion of the infarction border zone, reducing infarct size and protecting cardiac function after MI.

Harvard Citation style: Stieger, P., Daniel, J., Thoelen, C., Dutzmann, J., Knoepp, K., Guenduez, D., et al. (2017) Targeting of Extracellular RNA Reduces Edema Formation and Infarct Size and Improves Survival After Myocardial Infarction in Mice, Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease, 6(6), Article e004541. https://doi.org/10.1161/JAHA.116.004541

APA Citation style: Stieger, P., Daniel, J., Thoelen, C., Dutzmann, J., Knoepp, K., Guenduez, D., Aslam, M., Kampschulte, M., Langheinrich, A., Fischer, S., Cabrera-Fuentes, H., Wang, Y., Wollert, K., Bauersachs, J., Braun-Dullaeus, R., Preissner, K., & Sedding, D. (2017). Targeting of Extracellular RNA Reduces Edema Formation and Infarct Size and Improves Survival After Myocardial Infarction in Mice. Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease. 6(6), Article e004541. https://doi.org/10.1161/JAHA.116.004541