Irradiation abolishes smooth muscle investment into vascular lesions in specific vascular beds.
The long-term adverse effects of radiotherapy on cardiovascular disease are well documented. However, the underlying mechanisms responsible for this increased risk are poorly understood. Previous studies using rigorous smooth muscle cell (SMC) lineage tracing have shown abundant SMC investment into atherosclerotic lesions, where SMCs contribute to the formation of a protective fibrous cap. Studies herein tested whether radiation impairs protective adaptive SMC responses during vascular disease. To do this, we exposed SMC lineage tracing (Myh11-ERT2Cre YFP+) mice to lethal radiation (1,200 cGy) followed by bone marrow transplantation prior to atherosclerosis development or vessel injury. Surprisingly, following irradiation, we observed a complete loss of SMC investment in 100% of brachiocephalic artery (BCA), carotid artery, and aortic arch lesions. Importantly, this was associated with a decrease in multiple indices of atherosclerotic lesion stability within the BCA. Interestingly, we observed anatomic heterogeneity, as SMCs accumulated normally into lesions of the aortic root and abdominal aorta, suggesting that SMC sensitivity to lethal irradiation occurs in blood vessels of neural crest origin. Taken together, these results reveal an undefined and unintended variable in previous studies using lethal irradiation and may help explain why patients exposed to radiation have increased risk for cardiovascular disease.
['Newman|Alexandra Ac|AA|', 'Baylis|Richard A|RA|', 'Hess|Daniel L|DL|', 'Griffith|Steven D|SD|', 'Shankman|Laura S|LS|', 'Cherepanova|Olga A|OA|', 'Owens|Gary K|GK|']
D000818:Animals D001012:Aorta, Abdominal D050197:Atherosclerosis D001853:Bone Marrow D016026:Bone Marrow Transplantation D016122:Brachiocephalic Trunk D002454:Cell Differentiation D004195:Disease Models, Animal D006801:Humans D008297:Male D051379:Mice D000074085:Mice, Knockout, ApoE D009131:Muscle, Smooth, Vascular D032389:Myocytes, Smooth Muscle D014916:Whole-Body Irradiation
Atherosclerosis Radiation therapy Vascular Biology