Huang Xiangfeng, Yin Bo, Hu Qingzhou, Zheng Qinbo, Chen Bingbing, Wang Jiale, Ji Xinyu, Su Kun
Wenzhou Medical University, Zhejiang, China.
Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China.
Mol Neurobiol. 2025 Apr 29. doi: 10.1007/s12035-025-04987-2.
Cerebrovascular diseases have caused substantial social and economic burdens, and new treatment methods are urgently needed. Evaluating the feasibility of the use of antidiabetic drugs for treating cerebrovascular diseases is meaningful in this field. We designed a comprehensive study process that includes two-sample Mendelian randomization (MR), which uses genetic proxies for antidiabetic drug targets, summary-based MR (SMR) for mRNAs, and colocalization for drug target genes to assess their causal relationships with 10 cerebrovascular disease phenotypes. Seven of the eight main types of clinical antidiabetic drugs were identified, yielding eleven potential drug targets. Our study observed that sulfonylureas (KCNJ11) and metformin (GPD1) reduce the risk of stroke and that TZDs (PPARG) reduce the risk of hippocampal perivascular spaces. In addition, sulfonylureas can reduce the risk of certain cerebral small vessel disease. These results show that antidiabetic drugs have hypoglycemic properties and affect cerebrovascular health. Our study supports repurposing antidiabetic drugs as disease-modifying therapies to improve cerebrovascular health. Future research should focus on studying the role of drugs in different phenotypes of cerebrovascular diseases and explore the potential molecular mechanisms to analyze further the potential effects of antidiabetic drugs on cerebrovascular diseases.
脑血管疾病已造成巨大的社会和经济负担，因此迫切需要新的治疗方法。评估使用抗糖尿病药物治疗脑血管疾病的可行性在该领域具有重要意义。我们设计了一个全面的研究过程，包括两样本孟德尔随机化（MR），其使用抗糖尿病药物靶点的遗传代理，基于汇总数据的mRNA的MR（SMR），以及药物靶基因的共定位，以评估它们与10种脑血管疾病表型的因果关系。确定了八种主要类型的临床抗糖尿病药物中的七种，产生了十一个潜在的药物靶点。我们的研究观察到磺脲类药物（KCNJ11）和二甲双胍（GPD1）可降低中风风险，噻唑烷二酮类药物（PPARG）可降低海马血管周围间隙的风险。此外，磺脲类药物可降低某些脑小血管疾病的风险。这些结果表明，抗糖尿病药物具有降血糖特性，并影响脑血管健康。我们的研究支持将抗糖尿病药物重新用作改善脑血管健康的疾病修饰疗法。未来的研究应集中于研究药物在脑血管疾病不同表型中的作用，并探索潜在的分子机制，以进一步分析抗糖尿病药物对脑血管疾病的潜在影响。
