Hu Fengli, Guo Ruixue, Zhi Yaxin, Hu Haijuan, Tang Ting, Wang Pengfei, Xue Ling
Department of Cardiology, Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Internal Medicine, Hebei Medical University, Shijiazhuang, China.
Front Endocrinol (Lausanne). 2025 Apr 17;16:1561142. doi: 10.3389/fendo.2025.1561142. eCollection 2025.
Diabetic cardiomyopathy has a very high incidence and serious clinical consequences, making it an urgent clinical problem to be solved. Angiogenesis is a significant phenotype in the occurrence and development of diabetic cardiomyopathy, especially the damage to angiogenesis of cardiac microvessels, which is inextricably linked to the cardiac risk of diabetic patients. In the current basic and clinical research, there is still a lack of treatment methods that directly target the angiogenesis of diabetic cardiomyopathy. This study hopes to discover the key molecules related to diabetic cardiomyopathy and angiogenesis damage, to provide ideas for possible interventions.
Sequencing data of animals and cells were obtained from the GEO database, and differentially expressed genes were analyzed. Subsequently, the angiogenesis-related genes were clustered for functional and pathway analysis. Then, the microangiogenesis of the diabetic mice and the angiogenesis changes of high glucose-stimulated HUVECs were verified, and the top three genes related to diabetic cardiomyopathy and angiogenesis were verified using western blot.
24 differentially expressed genes associated with angiogenesis were found in GSE241565(human) and GSE215979(mice). Among them, 11 genes showed the same trend in the two databases. Then CD31 staining of diabetic mice hearts showed that microvascular angiogenesis was impaired, high glucose-stimulated HUVECs decreased tube formation, and wound healing migration was weakened. Finally, the top 3 genes most associated with diabetic cardiomyopathy were verified, and there was no significant difference between the changes of Edn1 and Lepr. At the same time, Efnb2 was significantly increased under high glucose stimulation.
Combined with the sequencing data of animal and cell models of diabetic cardiomyopathy, the differential genes associated with angiogenesis were screened. These findings not only elucidate a novel molecular axis linking angiogenesis damage to diabetic cardiomyopathy but also highlight Efnb2 as a potential therapeutic target.
糖尿病性心肌病发病率极高且临床后果严重，成为亟待解决的临床问题。血管生成是糖尿病性心肌病发生发展中的一个重要表型，尤其是心脏微血管的血管生成受损，这与糖尿病患者的心脏风险密切相关。在目前的基础和临床研究中，仍缺乏直接针对糖尿病性心肌病血管生成的治疗方法。本研究希望发现与糖尿病性心肌病及血管生成损伤相关的关键分子，为可能的干预措施提供思路。
从基因表达综合数据库（GEO数据库）获取动物和细胞的测序数据，并分析差异表达基因。随后，对血管生成相关基因进行聚类以进行功能和通路分析。然后，验证糖尿病小鼠的微血管生成以及高糖刺激的人脐静脉内皮细胞（HUVECs）的血管生成变化，并使用蛋白质免疫印迹法验证与糖尿病性心肌病和血管生成相关的前三个基因。
在GSE241565（人类）和GSE215979（小鼠）中发现了24个与血管生成相关的差异表达基因。其中，11个基因在两个数据库中呈现相同趋势。然后，糖尿病小鼠心脏的CD31染色显示微血管生成受损，高糖刺激的HUVECs管腔形成减少，伤口愈合迁移减弱。最后，验证了与糖尿病性心肌病最相关的前3个基因，内皮素1（Edn1）和瘦素受体（Lepr）的变化之间无显著差异。同时，在高糖刺激下，埃芬B2（Efnb2）显著增加。
结合糖尿病性心肌病动物和细胞模型的测序数据，筛选出了与血管生成相关的差异基因。这些发现不仅阐明了一条将血管生成损伤与糖尿病性心肌病联系起来的新分子轴，还突出了Efnb2作为潜在治疗靶点的地位。
