Increase in proliferation of adventitial fibroblasts at early stage of atherosclerosis in apoE(-/-) mice

AIM: To study the relationship between the proliferation of adventitial fibroblasts and the early formation of atherosclerotic lesion. METHODS: ApoE(-/-) mice and wild-type C57BL/6 black mice (6-week old) were used in this experiment. 5-Bromo-2-deoxyuridine (BrdU) was administered 24 h before the animals were sacrificed at time points of 0, 2, 4 or 10 weeks after hyperlipidic diet, respectively. The ascending aorta was removed for serial sectioning. The morphological changes of the aortic tissues were observed under microscope with HE staining. Some sections of the aorta were used to observe the BrdU labeling in the adventitia and intima at different time points by the method of immunohistochemistry. In addition the arterial adventitial fibroblasts derived from apoE(-/-) mice and C57BL/6 mice after hyperlipidic diet for 2 weeks were cultured. The proliferation of the cells was examined by BrdU incorporation. The cell cycle was examined by flow cytometry. RESULTS: In vivo the BrdU-labeled cells were first found in the adventitia of apoE(-/-) mice after feeding with hyperlipidic diet for 2 weeks, the time point that no visible intimal lesion formation was found, and then subsequently emerged in the intimal lesion. No BrdU labeling was observed in C57BL/6 mice at any time point. The number of BrdU labeled cells in the adventitial fibroblasts of apoE(-/-) mice was significantly higher than that in C57BL/6 mice in vitro (P<0.01). The adventitial fibroblasts of apoE(-/-) mice exhibited higher percentages of S and G₂/M phases than those in C57BL/6 mice (P<0.05). CONCLUSION: The proliferation of arterial adventitial fibroblasts might participate in the early formation of atherosclerotic lesions.