Lactylation-Related Gene CALM1 Promotes Aortic Dissection via Immune Microenvironment Remodeling: Insights from Bioinformatics and Clinical Evidence

Zhiming Yu,* Yue Pan,* Xiaoyu Qian,* Xuesong Zhang, Zhen Zhu, Qun Xue, Weizhang Xiao Department of Cardiovascular Surgery, Affiliated Hospital and Medical School of Nantong University, Nantong, 226001, China*These authors contributed equally to this workCorrespondence: Qun Xue, Email [email protected] Weizhang Xiao, Email [email protected]: Aortic dissection (AD) represents a life-threatening cardiovascular condition with a high mortality rate. Extensive research has implicated inflammation as a pivotal factor in the development of aortic dissection. Lactylation, a process implicated in various inflammatory responses, play a critical role in several cardiovascular diseases. However, the specific role of lactylation-related genes in the pathogenesis of AD remains largely unexplored.Methods: We downloaded and integrated two AD-related datasets (GSE 52093 and GSE 98770) from the GEO database. Subsequently, we pinpointed hub genes associated with lactylation, conducted a comprehensive analysis of their functional implications, and examine the correlation between their expression levels and immune infiltration. Furthermore, we utilized single-cell sequencing data to compare the lactylation levels across various immune cell types between AD patients and healthy individuals.Results: Our analysis identified three hub genes (CALM1, PARP1, and PTBP1) that are strongly associated with lactylation in AD. Importantly, we found a robust correlation between the expression levels of these hub genes and the extent of immune cell infiltration. Single-cell sequencing data further highlighted marked differences in lactylation levels among diverse immune cell types between AD patients and healthy individuals. Notably, the lactylation levels of immune cells in the aortic tissues of AD patients were significantly elevated. In clinical sample validation, the expression of CALM1, but not PARP1 and PTBP1, showed significant differences between the two groups.Conclusion: Our study unveils significant differences in lactylation levels within the immune cells of aortic tissue between AD patients and healthy individuals. Moreover, we provide experimental validation that the lactylation-related gene CALM1 may serve as a promising biomarker for the diagnosis of AD, offering new insights into the pathogenesis and potential diagnostic approaches for this deadly condition.Keywords: aortic dissection, lactylation, immune infiltration, biomarker, molecular docking