<b>Rnd3 Ameliorates Diabetic Cardiac Microvascular Injury via Facilitating Trim40-mediated Rock1 Ubiquitination</b>

• DOI: 10.2337/figshare.28164029
• Publication Date: 2025-01-10T16:04:47Z
• Authors: Jie Lin; Xuebin Zhang; Wen Ge; Yu Duan; Xiao Zhang; Yan Zhang; Xinchun Dai; Mengyuan Jiang; Xiaohua Zhang; Jiye Zhang; Huanhuan Qiang; Dongdong Sun
• Keywords: ROCK1

&lt;p dir="ltr"&gt;Diabetic microvascular dysfunction is evidenced by disrupted endothelial cell junctions and increased permeability. However, effective strategies against these injuries remain scarce. In this study, the type 2 diabetes mouse model was established high-fat diet combined with streptozotocin injection in Rnd3 endothelial-specific transgenic knockout mice. Echocardiography employed to evaluate cardiac function. Microvascular corrosion casts, lanthanum nitrate perfusion, trans-endothelial electrical resistance, FITC-dextran permeability assay laser speckle contrast imaging were performed integrity of RNA sequencing, mass spectrometry, co-immunoprecipitation, immunofluorescence molecular docking used explore downstream regulators Rnd3. Evidence from gain/loss-of-function studies denoted a protective role for diabetic heart. Endothelial-specific deletion significantly exacerbated coronary barrier under conditions, while overexpression effectively prevented effects. Furthermore, also attenuated mice, as indicated LVEF, LVFS, E/A ratio. inhibited CMECs apoptosis migration response HG-PA challenge. Rock1 activity MLC phosphorylation treated stimulus. Mechanically, recruited interacted E3 ubiquitin ligase Trim40 which further facilitated degradation Rock1, thus inhibiting hyperpermeability HG-PA-stimulated CMECs. cardioprotective effects largely abrogated deficiency conditions. Collectively, alleviates hyperpermeability, maintains integrity, mitigates regulating Rock1/MLC signaling pathway state DCM.&lt;/p&gt;