Targeting the E3 ligase RLIM to regulate VSMC phenotypic switching in vascular aging:implications for cold stress
Wenqian Jiang
Madi Guo
Xu Wang
Xin Liu
Yong Zhang
State Key Laboratory of Frigid Zone Cardiovascular Diseases(SKLFZCD),Department of Pharmacology,College of Pharmacy,and Department of Cardiology,the Second Affiliated Hospital,Harbin Medical University,Harbin 150081,China;State Key Laboratory-Province Key Laboratories of Biomedicine-Pharmaceutics of China,and Key Laboratory of Cardiovascular Research,Ministry of Education,College of Pharmacy,Harbin 150081,China;Research Unit of Noninfectious Chronic Diseases in Frigid Zone(2019RU070),Chinese Academy of Medical Sciences,Harbin 150081,China
摘要：Objective:Cold exposure may impair vascular function and promote cardiovascular diseases(CVDs)by causing vasoconstriction,hemodynamic changes,and sympathetic activation.Vascular aging,a key factor in CVDs,is linked to phenotypic switching of vascular smooth muscle cells(VSMCs),but its regulatory mechanisms are not fully understood.Materials and methods:We used aged C57BL/6 mice and D-galactose-induced senescent VSMCs to investigate the role of the E3 ligase RLIM in arterial aging.RLIM knockdown and overexpression in vivo were achieved using adeno-associated virus(AAV)vectors.Vascular aging and stiffness were assessed using β-galactosidase staining,pulse wave velocity(PWV)measurements,and histological staining.Proteomic profiling was conducted to identify key protein alterations associated with vascular dysfunction and to elucidate underlying mechanisms.Results:RLIM expression was significantly upregulated in the aortae of aged mice and D-galactose-induced senescent VSMCs.AAV-mediated RLIM knockdown significantly attenuated vascular aging,as evidenced by vascular ultrasound and histological assessments.Conversely,RLIM overexpression exacerbated vascular damage.Proteomic analysis revealed that RLIM knockdown in VSMCs from aged mice resulted in increased expression of smooth muscle contractile proteins and decreased levels of inflammatory markers,indicating a phenotypic shift toward a more contractile state.Conclusion:These findings identify RLIM as a key regulator of arterial aging and a promising therapeutic target for age-related cardiovascular diseases.
机标关键词：stressvsmccoldagingimplicationsligasephenotypicregulate
论文发表日期：2025-09-30
在线出版日期：2025-11-28（本平台首次上网日期，不代表文献的发表时间）
页数：10( 147-156 )
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