Scholarlink

<p>Vascular cognitive impairment and dementia (VCID) is increasingly recognized as a consequence of chronic cerebrovascular dysfunction, including cerebral small vessel disease and clinically defined entities such as post-stroke cognitive impairment (PSCI). Clinical and experimental studies indicate that endothelial injury and maladaptive microvascular remodeling can precede cognitive decline through cerebral blood flow dysregulation, impaired neurovascular coupling, and blood–brain barrier (BBB) disruption, with downstream neuroinflammatory amplification. A recurring feature across these settings is redox imbalance: reactive oxygen species (ROS) derived from mitochondria, NADPH oxidases, and uncoupled endothelial nitric oxide synthase act not only as mediators of oxidative injury but also as compartmentalized signaling cues that remodel endothelial transcriptional and epigenetic states. Here, I review how redox-sensitive modules—including TGF-β/Smad, NF-κB, HIF-1α, Wnt/β-catenin, and Notch signaling, together with chromatin regulation and non-coding RNAs—may initiate or stabilize endothelial-to-mesenchymal transition (EndMT) and partial EndMT-like programs during chronic vascular stress. I then discuss how EndMT-like reprogramming could contribute to BBB fragility, extracellular matrix remodeling, vascular stiffening, hypoperfusion, and neurovascular dysfunction, while highlighting priorities for in vivo causal testing and potential reversibility of partial EndMT. Finally, I map key mechanistic nodes to potential therapeutic classes to inform precision strategies targeting putative pathogenic redox–EndMT circuits rather than global oxidative stress.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

EndMT in vascular cognitive impairment and dementia: mechanisms, evidence gaps, and therapeutic opportunities

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月4日

查看全文
  • Juhyun Song

摘要

Vascular cognitive impairment and dementia (VCID) is increasingly recognized as a consequence of chronic cerebrovascular dysfunction, including cerebral small vessel disease and clinically defined entities such as post-stroke cognitive impairment (PSCI). Clinical and experimental studies indicate that endothelial injury and maladaptive microvascular remodeling can precede cognitive decline through cerebral blood flow dysregulation, impaired neurovascular coupling, and blood–brain barrier (BBB) disruption, with downstream neuroinflammatory amplification. A recurring feature across these settings is redox imbalance: reactive oxygen species (ROS) derived from mitochondria, NADPH oxidases, and uncoupled endothelial nitric oxide synthase act not only as mediators of oxidative injury but also as compartmentalized signaling cues that remodel endothelial transcriptional and epigenetic states. Here, I review how redox-sensitive modules—including TGF-β/Smad, NF-κB, HIF-1α, Wnt/β-catenin, and Notch signaling, together with chromatin regulation and non-coding RNAs—may initiate or stabilize endothelial-to-mesenchymal transition (EndMT) and partial EndMT-like programs during chronic vascular stress. I then discuss how EndMT-like reprogramming could contribute to BBB fragility, extracellular matrix remodeling, vascular stiffening, hypoperfusion, and neurovascular dysfunction, while highlighting priorities for in vivo causal testing and potential reversibility of partial EndMT. Finally, I map key mechanistic nodes to potential therapeutic classes to inform precision strategies targeting putative pathogenic redox–EndMT circuits rather than global oxidative stress.