Novel Epigenetic Mechanisms of Endogenous CSE/H2S in Smooth Muscle Cells for Abdominal Aortic Aneurysm
Background: The incidence of abdominal aortic aneurysm is increasing year by year. Its rupture is associated with a high mortality rate, and recurrence is extremely likely even after treatment. The gasotransmitter hydrogen sulfide (H2S) and its key generating enzyme, cystathionine -? -lyase (CSE), possess anti -inflammatory, antioxidant, and anti -apoptotic properties, and have a cardiovascular protective effect. However, the role of CSE in AAA development and progression remains elusive. Methods: Using smooth muscle cell-specific CSE-knockout mice as models and angiotensin II, ß-aminopropionitrile as inducers, it was found that CSE knockout in smooth muscle cells increased AAA incidence and mortality. Experimental results confirmed smooth muscle endogenous CSE/H2S is involved in AAA development. However, its molecular mechanism remains a key scientific issue urgently needing solution. Thus, whole-genome RNA sequencing analysis was carried out on primary aortic smooth muscle cells isolated from Ang II-stimulated C57BL/6J mice (CSE WT)  and global CSE-knockout mice (CSE KO) to identify potential key downstream genes regulated by CSE. Results: The RNA - seq data highlighted the crucial role of CSE in the regulation of extracellular matrix and the PRC complex, which has implications for the development of AAA. Overall design: Primary aortic smooth muscle cells isolated from C57BL/6J mice and global CSE - knockout mice were stimulated with angiotensin II for 24 hours. Subsequently, we performed RNA sequencing to explore the changes in the gene expression profile after the reduction of CSE levels. Our aim was to elucidate the downstream effects of CSE deficiency on the transcriptome of vascular smooth muscle cells, so as to gain in - depth insights into its regulatory mechanisms in abdominal aortic aneurysm (AAA).