Work

Myofibrillogenesis Regulator-1 in Smooth Muscle Cells Modulates Inflammation Signaling Pathways via Regulating ROCK1 Ubiquitination and Degradation to Impact Aortic Dissection

Year: 2025

Type: article

Abstract: Background: Aortic dissection (AD) is a life-threatening cardiovascular emergency and currently lacks effective drug treatment. Inflammation is a critical mechanism in the development of AD, and identifying specific molecular targets to regulate inflammation is crucial for stopping its progression. This study aimed to investigate the role of MR-1 and ROCK1 in the regulation of inflammation in AD and their potentialities as therapeutic targets. Methods: Researchers performed protein immunoblotting on aortic wall tissue from 10 patients who underwent aortic arch replacement and 10 patients who underwent coronary artery bypass grafting to examine the expression levels of MR-1, ROCK1, and inflammatory pathways in the aortas. In vitro experiments, human aortic smooth muscle cells were extracted, and an in vitro dissection model was constructed with angiotensin II. siRNA silencing studies were performed to investigate the effects of MR-1 and ROCK1 on the development of AD and their interconnections. Results: Analysis of aortic tissues revealed significantly elevated levels of MR-1 and ROCK1 in AD patients, and meanwhile the inflammatory indexes showed the same trend. Furthermore, it was observed that overexpression of MR-1 and ROCK1 facilitated smooth muscle cell phenotypic transformation and augmented matrix metalloproteinase release in in vitro settings through inflammatory pathway activation. The relationship between MR-1 and ROCK1 was elucidated, too. Conclusion: MR-1 and ROCK1 overexpression is associated with the occurrence and development of AD through inflammation. This study highlights the role of inflammation in AD development and tap the potentiality of using MR-1 and ROCK1 as targets to alleviate AD development.

Source: Journal of Inflammation Research

DOI: 10.2147/jir.s485163