Elucidating Molecule-Crosstalk of Neutrophil Extracellular Traps Between Cardiovascular Disease and Psoriasis: Insights Into Mendelian Randomization, Single-Cell RNA Analysis, Shared Targets and the Role of Resveratrol

Xiaojun Jin,1,2,* Yun Zhang,3,* Gaofeng Qin,4 Xinyan Fang,5 Xinnan Zhang,6 Jialin Sun,5 Min Zhou,1 Xuecheng Tong,1 Yuan Xue,1 Hui Yang,1 Weihong Tian1 1Department of Clinical Technology Laboratory, Changzhou Clinical College of Xuzhou Medical University, Changzhou Third People’s Hospital, Changzhou, Jiangsu, 213000, People’s Republic of China; 2Department of Clinical Medicine, School of Medicine, Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 3Department of Ophthalmology, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, Guangdong, 510000, People’s Republic of China; 4Department of Life Science Institute, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 5School of Statistics, East China Normal University, Shanghai, 200062, People’s Republic of China; 6School of Teacher Education, Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weihong Tian, Changzhou Clinical College of Xuzhou Medical University, Changzhou Third People’s Hospital, Changzhou, Jiangsu, 213000, People’s Republic of China, Email [email protected]: Left ventricular hypertrophy (LVH) associated with hypertension and psoriasis (PSO) are linked by poor prognosis. Neutrophil extracellular traps (NETs) are implicated in both conditions, but the mechanisms remain unclear.Methods: We integrated bulk and single-cell RNA sequencing, mendelian randomization, immune microenvironment analysis, and molecular docking to explore the molecular interactions between LVH and PSO, focusing on NET-related pathways. Prediction models were also developed, and gene function was validated through in vivo and in vitro experiments.Results: Our findings identified NETs-associated genes, AKT serine/threonine kinase 1 (AKT1), and receptor-interacting protein kinase 1 (RIPK1), regulating inflammation, fibroblast activation, and apoptosis in LVH and PSO. Functional enrichment analysis revealed mitochondrial metabolic disorders and extensive inflammation as the most prominent shared features of LVH and PSO diseases. Additionally, resveratrol exhibited a high binding affinity to the AKT1 and RIPK1 proteins. Functional validation showed that knockdown of AKT1 reduced LVH cell hypertrophy and PSO cell apoptosis.Conclusion: This study highlights molecular pathways linking LVH and PSO, suggesting novel targets for treating cardiac involvement in PSO patients with LVH.Keywords: molecular crosstalk, hypertrophy, psoriasis, neutrophil extracellular traps, molecular docking