Severe coronary artery stenoses and reduced coronary flow velocity reserve in atherosclerotic mouse model: Doppler echocardiography validation study

ObjectiveGenetically modified hyperlipidemic mice are increasingly used as an animal model of atherosclerosis, but their coronary artery disease remains poorly characterized. Furthermore, non-invasive tools to detect functional consequences of coronary lesions remain to be tested in mice. Coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography provides a hemodynamic measure of coronary artery stenosis severity in humans. Thus, we applied Doppler echocardiography in atherosclerotic mice to study the relationship between CFVR and histologically determined coronary artery narrowing.MethodsAtherosclerotic LDLR/ApoB48 double knockout mice of 58–72 weeks age (n = 12) and age-matched C57BL/6 mice (n = 5) were studied. CFVR was measured in anesthetized mice by Doppler echocardiography in the middle left coronary artery (LCA) during adenosine-induced maximal vasodilatation. Histopathology of proximal and middle LCA was studied in serial tissue sections.ResultsAll LDLR/ApoB48 double knockout mice had atherosclerotic lesions in the proximal, but not in the middle LCA causing various degrees of luminal narrowing (30–97%). No lesions were found in controls. Compared with controls, CFVR was significantly reduced in the atherosclerotic mice (2.3 ± 0.5 vs. 1.7 ± 0.5, p = 0.02). There was a negative correlation between CFVR and the amount of luminal narrowing (r = −0.91, p = 0.001). Average CFVR was consistently lower in mice that had ≥70% than <70% stenosis (1.3 ± 0.1, n = 7 vs. 2.2 ± 0.4, n = 5, p = 0.0002).ConclusionsLDLR/ApoB48 double knockout mice are characterized with histologically severe coronary artery narrowings. Reduced CFVR is a consistent feature of these lesions. Doppler echocardiography of coronary artery flow can be used to detect flow-limiting stenosis in living atherosclerotic mice.