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bioRxiv · 10.1101/2022.09.03.506447

Cardiovascular Hemodynamics in Mice with Tumor Necrosis Factor Receptor - Associated Factor 2 Mediated Cytoprotection in the Heart

Marshall, A. G.·Neikirk, K.·Vue, Z.·Beasley, H. K.·Garza-Lopez, E.·Vang, L.·Barongan, T.·Evans, Z.·Anudokem, J.·Pham, T. T.·Gomez, J. A.·Exil, V.·Dai, D.-F.·Entman, M. L.·Taffet, G. E.·Hinton, A.·Reddy, A. K.
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Abstract

Many studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, and end-diastolic diameter, and others, are used to assess cardiac function, their dependency on loading conditions somewhat limit their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include of the interaction between the ventricle and the aorta (ventriculo-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity. We measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in mouse model of cardiac-restricted low levels TRAF2 overexpression that conferred cytoprotection in the heart. While previous studies reported that response to myocardial infraction and reperfusion was improved in the TRAF2 overexpressed mice, we found that TRAF2 mice had significantly lower cardiac systolic velocities and accelerations, diastolic atrial velocity, lower aortic pressures and rate-pressure product, lower LV contractility and relaxation, and lower stroke work when compared to littermate control mice. Also, we found significantly longer aortic ejection time, isovolumic contraction and relaxation times, and significantly higher mitral early/atrial ratio, myocardial performance index, and ventricular vascular coupling in the TRAF2 overexpression mice compared to their littermate controls. We found no significant differences in the aortic impedance and pulse wave velocity. While the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate a diminished cardiac function in these mice.

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Marshall, A. G., Neikirk, K., Vue, Z., Beasley, H. K., Garza-Lopez, E., Vang, L., Barongan, T., Evans, Z., Anudokem, J., Pham, T. T., Gomez, J. A., Exil, V., Dai, D.-F., Entman, M. L., Taffet, G. E., Hinton, A., Reddy, A. K.. 2022-09-06. Cardiovascular Hemodynamics in Mice with Tumor Necrosis Factor Receptor - Associated Factor 2 Mediated Cytoprotection in the Heart. https://doi.org/10.1101/2022.09.03.506447

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