Ultrasonographic Characterization of thedb/dbMouse: An Animal Model of Metabolic Abnormalities

Abstract

The availability of an animal model able to reliably mirror organ damage occurring in metabolic diseases is an urgent need. These models, mostly rodents, have not been fully characterized in terms of cardiovascular, renal, and hepatic ultrasound parameters, and only sparse values can be found in literature. Aim of this paper is to provide a detailed, noninvasive description of the heart, vessels, liver, and kidneys of the db/db mouse by ultrasound imaging. Sixteen wild type and thirty-four db/db male mice (11-week-old) were studied. State-of-the-art ultrasound technology was used to acquire images of cardiovascular, renal, and hepatic districts. A set of parameters describing function of the selected organs was evaluated. db/db mice are characterized by systolic and diastolic dysfunction, confirmed by strain analysis. Abdominal aortic and carotid stiffness do not seem to be increased in diabetic rodents; furthermore, they are characterized by a smaller mean diameter for both vessels. Renal microcirculation is significantly compromised, while liver steatosis is only slightly higher in db/db mice than in controls. We offer here for the first time an in vivo detailed ultrasonographic characterization of the db/db mouse, providing a useful tool for a thoughtful choice of the right rodent model for any experimental design.

Endothelial Dysfunction and Passive Changes in the Aorta and Coronary Arteries of Diabetic db/db Mice

“…In the present study, the maximum stiffness of the aorta was decreased in the male db/db mice consistent with the decreased wall thickness, while the maximal elastic modulus remained the same. The aortic stiffness evaluated in vivo also appeared unchanged consistent with a recent study (Faita et al, 2018). The stress-strain relationship was rightward shifted in coronary arteries from male db/db mice.…”

“…Diabetic cardiomyopathy can occur in the hypertrophic and/or the dilated form or as restrictive cardiomyopathy in diabetic patients with preserved ejection fraction (Seferoviae and Paulus, 2015). In db/db mice, a recent study observed low LV mass and systolic dysfunction suggesting restrictive cardiomyopathy rather than hypertrophic remodeling of the heart in db/db animals (Faita et al, 2018). In the present study, heart weight was unaltered expressed as raw weight and as a ratio to tibia length.…”

“…In aorta from diabetic ob/ob mice, the media thickness is increased and this is ascribed to an increased amount of proteoglycans in the vessel wall (Okon et al, 2003), while in db/db mice, wall thickness of the aorta was reported to be similar to that of the control mice (Guo et al, 2005). In vitro studies reported larger diameters of stretched aorta segments from db/db mice (Piercy and Taylor, 1998), but recent in vivo studies suggested similar aortic diameters measured with echocardiography (Faita et al, 2018). In the present study, the diameters of the aorta in db/db versus control mice were similar using echocardiography, and in segments without active contribution from smooth muscle cells.…”

HuangqiGuizhiWuwu Decoction Prevents Vascular Dysfunction in Diabetes via Inhibition of Endothelial Arginase 1

“…Blood glucose and body weight levels of each animal were measured at the first day, second, eighth, and tenth weeks of STZ injection. Both hemodynamic function and vascular wall function were assessed by ultrasound as previously described (Bhatta et al, 2015;Kenwright et al, 2015;Faita et al, 2018;Esfandiarei et al, 2019). Vascular endothelial function was measured by myograph as previously described (Yao et al, 2013).…”

“…The function of the vascular system can be regulated by both hemodynamic function and vascular wall function (Pugsley and Tabrizchi, 2000;Lee, 2013). In diabetes patients and animal models, abnormal characteristics of hemodynamic and vascular wall function have been reported in vivo studies by non-invasive ultrasonography (Cardoso et al, 2015;Faita et al, 2018;Chirinos et al, 2019;Kozera et al, 2019). In this study, we chose mean velocity (MV) to represent the kinetic energy of the blood flow, pulsatility index (PI) to evaluate the vascular resistance and pulse wave velocity (PWV) to predict vascular wall stiffness (Panaritis et al, 2005;Lee, 2013;Alman et al, 2018), which are commonly used in evaluating the function of vascular system.…”