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 -γ -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, β-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.