Vasa vasorum neovascularization and lesion distribution among different vascular beds in ApoE^−/−/LDL^−/− double knockout mice

Abstract 

Objective

To increase understanding of the substantial variation in the incidence and distribution of atherosclerotic lesions among different vascular beds. In view of some evidence that there are different distributions of adventitial vasa vasorum (VV) in different vascular beds, and that this correlates with lesion formation, we explored this possible linkage in apoE^−/−/LDL^−/− double knockout mice, which develop VV at age beyond 16 weeks.

Methods and results

Samples from the aorta, coronary, pulmonary, carotid, and cerebral arteries in apoE^−/−/LDL^−/− double knockout mice at the age of 16–80 weeks (n=24) were scanned by micro-CT. Using those 3D images, we characterized plaque volume, vessel luminal diameter and VV luminal volume along the vessels. Results were complemented by histology.

Advanced atherosclerotic lesions were found in the aorta, pulmonary artery and carotid artery. Occluded intramyocardial vessels (vessel diameter ∼0.1mm) with concomitant myocardial infarctions were found without any evidence of adventitial VV neovascularization. VV luminal volume follows the order: aorta>pulmonary arteries>carotid arteries. VV were only observed in atherosclerotic diseased vessels with a lumen diameter>0.4mm. No atherosclerotic lesions, and no VV, were observed in cerebral arteries.

Conclusion

The spatial heterogeneity in the development of atherosclerotic lesions among different vascular beds is linked to appearance of VV and to vessel lumen diameter.

Keywords: Atherosclerosis, Inflammation, Vasa vasorum, Micro-CT, Imaging