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

Authors

Andrea G Marshall
Kit Neikirk
Zer Vue
Heather K Beasley
Edgar Garza-Lopez
Larry Vang
Taylor Barongan
Zoe Evans
Amber Crabtree
Elsie Spencer
Josephs Anudokem
Remi Parker
Jamaine Davis
Dominique Stephens
Steven Damo
Thuy T Pham
Jose A Gomez
Vernat Exil
Dao-Fu Dai
Sandra A Murray
Mark L Entman
George E Taffet
Antentor O Hinton
Anilkumar K Reddy

Publication Date

1-1-2023

Journal

Frontiers in Cardiovascular Medicine

DOI

10.3389/fcvm.2023.1064640

PMID

37229235

PMCID

PMC10203617

PubMedCentral® Posted Date

5-9-2023

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

systolic and diastolic function, myocardial performance index, ventricular-vascular coupling, arterial and left ventricular elastance, aortic impedance

Abstract

INTRODUCTION: 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, end-diastolic diameter, and others are used to assess cardiac function, their dependency on loading conditions somewhat limits their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include the interaction between the ventricle and the aorta (ventricular-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity.

METHODS: We measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in a mouse model of cardiac-restricted low levels of TRAF2 overexpression that conferred cytoprotection in the heart.

RESULTS: While previous studies reported that response to myocardial infarction 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, aortic pressures, rate-pressure product, LV contractility and relaxation, and 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.

DISCUSSION: While the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate diminished cardiac function in these mice.

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