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
Hypertension is a global public health issue and the leading cause of premature death in humans.Despite more than a century of research,hypertension remains difficult to cure due to its complex mechanisms involving mu...Hypertension is a global public health issue and the leading cause of premature death in humans.Despite more than a century of research,hypertension remains difficult to cure due to its complex mechanisms involving multiple interactive factors and our limited understanding of it.Hypertension is a condition that is named after its clinical features.Vascular function is a factor that affects blood pressure directly,and it is a main strategy for clinically controlling BP to regulate constriction/relaxation function of blood vessels.Vascular elasticity,caliber,and reactivity are all characteristic indicators reflecting vascular function.Blood vessels are composed of three distinct layers,out of which the endothelial cells in intima and the smooth muscle cells in media are the main performers of vascular function.The alterations in signaling pathways in these cells are the key molecular mechanisms underlying vascular dysfunction and hypertension development.In this manuscript,we will comprehensively review the signaling pathways involved in vascular function regulation and hypertension progression,including calcium pathway,NO-NOsGC-cGMP pathway,various vascular remodeling pathways and some important upstream pathways such as renin-angiotensin-aldosterone system,oxidative stress-related signaling pathway,immunity/inflammation pathway,etc.Meanwhile,we will also summarize the treatment methods of hypertension that targets vascular function regulation and discuss the possibility of these signaling pathways being applied to clinical work.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.
基金supported by the National Natural Science Foundation of China (No.81900404,No.81970355).
文摘Hypertension is a global public health issue and the leading cause of premature death in humans.Despite more than a century of research,hypertension remains difficult to cure due to its complex mechanisms involving multiple interactive factors and our limited understanding of it.Hypertension is a condition that is named after its clinical features.Vascular function is a factor that affects blood pressure directly,and it is a main strategy for clinically controlling BP to regulate constriction/relaxation function of blood vessels.Vascular elasticity,caliber,and reactivity are all characteristic indicators reflecting vascular function.Blood vessels are composed of three distinct layers,out of which the endothelial cells in intima and the smooth muscle cells in media are the main performers of vascular function.The alterations in signaling pathways in these cells are the key molecular mechanisms underlying vascular dysfunction and hypertension development.In this manuscript,we will comprehensively review the signaling pathways involved in vascular function regulation and hypertension progression,including calcium pathway,NO-NOsGC-cGMP pathway,various vascular remodeling pathways and some important upstream pathways such as renin-angiotensin-aldosterone system,oxidative stress-related signaling pathway,immunity/inflammation pathway,etc.Meanwhile,we will also summarize the treatment methods of hypertension that targets vascular function regulation and discuss the possibility of these signaling pathways being applied to clinical work.
