Validation of the murine aortic arch as a model to study human vascular diseases

Abstract

Although the murine thoracic aorta and its main branches are widely studied to gain more insight into the pathogenesis of human vascular diseases, detailed anatomical data on the murine aorta are sparse. Moreover, comparative studies between mice and men focusing on the topography and geometry of the heart and aorta are lacking. As this hampers the validation of murine vascular models, the branching pattern of the murine thoracic aorta was examined in 30 vascular corrosion casts. On six casts the intrathoracic position of the heart was compared with that of six younger and six older men of whom contrast-enhanced computer tomography images of the thorax were three-dimensionally reconstructed. In addition, the geometry of the human thoracic aorta was compared with that of the mouse by reconstructing micro-computer tomography images of six murine casts. It was found that the right brachiocephalic trunk, left common carotid artery and left subclavian artery branched subsequently from the aortic arch in both mice and men. The geometry of the branches of the murine aortic arch was quite similar to that of men. In both species the initial segment of the aorta, comprising the ascending aorta, aortic arch and cranial/superior part of the descending aorta, was sigmoidally curved on a cranial/superior view. Although some analogy between the intrathoracic position of the murine and human heart was observed, the murine heart manifestly deviated more ventrally. The major conclusion of this study is that, in both mice and men, the ascending and descending aorta do not lie in a single vertical plane (non-planar aortic geometry). This contrasts clearly with most domestic mammals in which a planar aortic pattern is present. As the vascular branching pattern of the aortic arch is also similar in mice and men, the murine model seems valuable to study human vascular diseases.

Fig. 1

Visual representations of the various angles that were measured concerning the intrathoracic position of the heart and the geometry of the aortic arch. (A) The deviations of the ventricular axis (1) and aortic arch (2) to the left of the median plane were measured on an anterior/ventral view. The same deviations (3 and 4, respectively) were also determined on a superior/cranial view. On a lateral view the deviation of the ventricular axis to ventral (5) and the angle between the ventricular axis and ascending aorta (6) were measured. (B) The angles at which the brachiocephalic trunk (aa-bc), left common carotid artery (aa-lc) and left subclavian artery (aa-ls) branch off from the aortic arch were measured on an anterior/ventral view. The angles between the ascending aorta and descending aorta at the level of the aortic bulb (aa-da) and between the ascending aorta and thoracic aorta after it had joined the vertebral column (aa-ta) were determined on a right lateral view.

Fig. 3

Ventral views of cast murine aortic arches showing the right internal thoracic artery (rit) either branching off from a long brachiocephalic trunk (bct) (left side of the figure) or from the right subclavian artery (rs) (right side of the figure) when the brachiocephalic trunk is very short (R and L = right and left side of the thorax, respectively). rcc, right common carotid artery; lcc, left common carotid artery; ls, left subclavian artery.

Fig. 2

Ventral view of a cast (left side of the figure) and schematically drawn (right side of the figure) murine aortic arch with its originating arteries (R and L = right and left side of the thorax, respectively). bct, brachiocephalic trunk; rit, right internal thoracic artery; rs, right subclavian artery; rcc, right common carotid artery; rv, right vertebral artery; rct, right cervical trunk; rsc, right superficial cervical artery; ra, right axillary artery; rb, right brachial artery; rtd, right thoracodorsal artery; lcc, left common carotid artery; ls, left subclavian artery; lit, left internal thoracic artery; lv, left vertebral artery; lct, left cervical trunk; lsc, left superficial cervical artery; la, left axillary artery; lb, left brachial artery; ltd, left thoracodorsal artery. Notice that the right internal thoracic artery in this specimen branches off from the long brachiocephalic trunk.

Fig. 4

Computerized 3D reconstructions of the hearts (left ventricles in men) and aortic arches of mice, younger and older men allowing the comparison of the geometry and intrathoracic position of these structures.

Fig. 5

Box plots showing the values of the various angles that were measured in mice, younger and older men as illustrated in Fig. 1A,B (A and B of the present figure, respectively). Values marked with the same symbol (*, ° or #) differ significantly from each other. The mean value is represented by the horizontal bar in the box, the box itself represents the interquartile range (25–75% of the values), and the minimal and maximal values are marked by the horizontal bars at the lower and upper ends of the box, respectively.