Key result
High-resolution vascular ultrasound detected reduced arterial wall elasticity and elevated pulse wave velocity in murine models of atherosclerosis and AAA, correlating with histological findings.
Why the study?
Multiple animal models exist for vascular diseases like atherosclerosis and aortic aneurysm, prompting the evaluation of high-resolution ultrasound for noninvasive monitoring of morphological and functional vascular changes in vivo.
High-resolution vascular ultrasound reliably detects functional and morphological arterial wall changes that correlate with histological collagen deposition in murine models of atherosclerosis and AAA.
Validates ultrasound metrics in murine atherosclerosis and AAA models; leaves open human translation.
Background Vascular diseases like atherosclerosis or aortic aneurysms are common pathologies in the western world, promoting various, potentially fatal conditions. Hence, a plethora of animal models have been developed to investigate underlying mechanisms and potential therapeutics. Here we evaluate high resolution (HR) ultrasound in mouse models of atherosclerosis and abdominal aortic aneurysm (AAA) for noninvasive monitoring of morphological and functional vascular changes in vivo . Methods Eight-week-old ApoE -/- mice were used for disease models. For induction of atherosclerosis, mice were fed a western diet over 12 weeks. To trigger AAA development, osmotic minipumps were implanted, permanently releasing Angiotensin II continuously for 28 days. All animals were on C57Bl6/J background. HR vascular ultrasound of the carotid artery or the abdominal aorta was performed, respectively. Images obtained were analyzed by a speckle tracking algorithm (VevoVasc software) and were correlated with histological analyses by Picro Sirius Red staining and automated collagen quantification. Results Arterial wall distensibility and global radial strain (GRS) as measures of arterial wall elasticity were reduced in the carotids of atherosclerotic mice as well as in the aortas of AAA mice. Pulse wave velocity (PWV) was elevated in both disease models. Intima-media thickness (IMT) was significantly increased in the atherosclerosis model. Matching those findings, area of the tunica media was enlarged in ApoE -/- mice fed a western diet, and in Angiotensin II treated mice as measured by automated image analysis, depicting higher collagen depositions in diseased arteries. Simple regression analysis revealed a strong correlation of media collagen content and area in AAA with IMT and GRS, respectively. In atherosclerosis, media collagen content significantly correlated with PWV and GRS, whereas wall distensibility was associated with the size of media area. Conclusion Vascular imaging using latest generation HR ultrasound devices is suitable to trace changes of arterial wall properties in murine models of atherosclerosis and AAA. Obtained results not only correlate with histological findings but deliver information on functional parameters which may be used as early disease and risk markers in a longitudinal experimental approach.
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Hof et al. (2022) studied Atherosclerosis and abdominal aortic aneurysm. High resolution (HR) vascular ultrasound vs. Histological analyses was evaluated on Morphological and functional vascular changes (arterial wall distensibility, GRS, PWV, IMT). High-resolution vascular ultrasound detected reduced arterial wall elasticity and elevated pulse wave velocity in murine models of atherosclerosis and AAA, correlating with histological findings.
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