Vascular smooth muscle cells (VSMC) are involved in many arterial diseases including atherosclerosis and aneurysm formation. VSMC accumulation and apoptosis have implications for atherosclerotic plaque stability and development. In a mouse model of inducible VSMC-specific apoptosis, chronic apoptosis of VSMC has been shown to induce features of plaque instability including fibrous cap thinning, plaque calcification, necrotic core enlargement, medial erosion, elastin breaks and accelerated atherogenesis of established atherosclerotic plaques. Based on previous findings, we questioned the role of medial VSMC in the development of atherosclerotic lesions. To test our research question, ApoE-/- and SM22α-hDTR/ApoE-/- mice were injected with 1 ng diphtheria toxin (DT) /gram bodyweight for 3 weeks to induce medial VSMC cytopenia. After 3 weeks, DT treatment was arrested, mice started a Western type diet (0.25% cholesterol) and were sacrificed after 6 and 18 weeks, respectively. The aortic arch including branches was excised and analysed (immune)histochemically. VSMC cytopenia after 3 weeks of DT treatment was verified by analysing vessel cellularity (cells/mm²) in both control (ApoE-/-) and SM22α-hDTR/ApoE-/- mice. A 2-fold decrease in cellularity was observed in SM22α-hDTR/ApoE-/- mice as compared to the control. Atherosclerotic plaque size was quantified on HE stained sections. SM22α-hDTR/ApoE-/- mice displayed significantly accelerated plaque development as compared to control mice. In vitro, induction of apoptosis by ABT737 significantly induced calcification of primary human VSMC whereas ZVAD significantly inhibited calcification. Additional, conditioned medium from both apoptotic and calcified VSMC cultures served as a chemoattractant for macrophages. In vivo, these in vitro findings may explain the pro-inflammatory phenotype of atherosclerotic plaques. In conclusion, medial VSMC cytopenia results in accelerated development of established atherosclerotic plaques, with increased plaque calcification and vessel stenosis.
- vascular smooth muscle cell
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.