Arterial stiffness is a critical factor in cardiovascular and cerebrovascular events,yet clinical practice lacks specific therapeutic targets and biomarkers for its assessment.Hyperlipidemia closely correlates with ar...Arterial stiffness is a critical factor in cardiovascular and cerebrovascular events,yet clinical practice lacks specific therapeutic targets and biomarkers for its assessment.Hyperlipidemia closely correlates with arterial stiffness,and we observed elevated CCAAT/enhancer-binding protein β(C/EBPβ)expression in atherosclerotic mouse arterial walls.As the arterial medial layer predominantly consists of vascular smooth muscle cells(VSMCs),C/EBPβ's role in VSMCs under hyperlipidemia remains unclear.Our findings demonstrate that cholesterol-induced phenotypic transition of contractile VSMCs to macrophage-like cells coincides with C/EBPβupregulation and activation.The activation of C/EBPβ is closely related to cellular assembly and organization,regulating the cytoskeleton via Disheveled-associated activator of morphogenesis 1(Daam1).Conditional knockout of C/EBPβ in VSMCs of ApoE−/−mice alleviated hyperlipidemia-induced vascular remodeling and reduced the elevation of aortic pulse wave velocity.Additionally,C/EBPβ-regulated cytokine platelet-derived growth factor-CC(PDGF-CC)is correlated with brachial-ankle pulse wave velocity in humans.These results indicate that the activation of C/EBPβ promotes the transition of VSMCs from a contractile phenotype to a macrophagelike phenotype by regulating morphological changes,and C/EBPβ activation contributes to hyperlipidemia-induced arterial stiffness.PDGF-CC exhibited a significant association with arterial stiffness and may serve as a promising indicator of arterial stiffness in humans.Our study reveals molecular mechanisms behind hyperlipidemia-induced arterial stiffness and provides potential therapeutic targets and biomarkers.展开更多
基金funded by the National Natural Science Foundation of China(No.81900404)Natural Science Foundation of Sichuan Province(NO.24NSFSC2535)Science and Technology Program of Tibet Autonomous Region(NO.XZ202303ZY0004G).
文摘Arterial stiffness is a critical factor in cardiovascular and cerebrovascular events,yet clinical practice lacks specific therapeutic targets and biomarkers for its assessment.Hyperlipidemia closely correlates with arterial stiffness,and we observed elevated CCAAT/enhancer-binding protein β(C/EBPβ)expression in atherosclerotic mouse arterial walls.As the arterial medial layer predominantly consists of vascular smooth muscle cells(VSMCs),C/EBPβ's role in VSMCs under hyperlipidemia remains unclear.Our findings demonstrate that cholesterol-induced phenotypic transition of contractile VSMCs to macrophage-like cells coincides with C/EBPβupregulation and activation.The activation of C/EBPβ is closely related to cellular assembly and organization,regulating the cytoskeleton via Disheveled-associated activator of morphogenesis 1(Daam1).Conditional knockout of C/EBPβ in VSMCs of ApoE−/−mice alleviated hyperlipidemia-induced vascular remodeling and reduced the elevation of aortic pulse wave velocity.Additionally,C/EBPβ-regulated cytokine platelet-derived growth factor-CC(PDGF-CC)is correlated with brachial-ankle pulse wave velocity in humans.These results indicate that the activation of C/EBPβ promotes the transition of VSMCs from a contractile phenotype to a macrophagelike phenotype by regulating morphological changes,and C/EBPβ activation contributes to hyperlipidemia-induced arterial stiffness.PDGF-CC exhibited a significant association with arterial stiffness and may serve as a promising indicator of arterial stiffness in humans.Our study reveals molecular mechanisms behind hyperlipidemia-induced arterial stiffness and provides potential therapeutic targets and biomarkers.
