Effect of Cyclic Stretch on Vascular Endothelial Cells and Abdominal Aortic Aneurysm (AAA): Role in the Inflammatory Response

• Published in: International journal of molecular sciences 2019-01, Vol.20 (2), p.287
• Main Authors: Ramella, Martina, Bertozzi, Giulia, Fusaro, Luca, Talmon, Maria, Manfredi, Marcello, Catoria, Marta Calvo, Casella, Francesco, Porta, Carla Maria, Boldorini, Renzo, Fresu, Luigia Grazia, Marengo, Emilio, Boccafoschi, Francesca
• Format: Article
• Language: English
• Subjects: Abdomen; Aneurysms; Aortic Aneurysm, Abdominal - immunology; Aortic Aneurysm, Abdominal - metabolism; Aortic Aneurysm, Abdominal - physiopathology; Aortic aneurysms; Bioreactors; Calcification; Cell adhesion & migration; Cell Culture Techniques - instrumentation; Cell Line; Endothelial cells; Endothelial Cells - immunology; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelium; Flow velocity; Fluid dynamics; Gene Regulatory Networks; Humans; Inflammation; Inflammatory response; Matrix Metalloproteinase 9 - metabolism; Models, Biological; Morphology; Oxidative Stress; Physiology; Proteins; Rupture; Rupturing; Stiffening; Stress, Mechanical; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Turbulent flow
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20020287

Abdominal aortic aneurysm (AAA) is a focal dilatation of the aorta, caused by both genetic and environmental factors. Although vascular endothelium plays a key role in AAA progression, the biological mechanisms underlying the mechanical stress involvement are only partially understood. In this study, we developed an model to characterize the role of mechanical stress as a potential trigger of endothelial deregulation in terms of inflammatory response bridging between endothelial cells (ECs), inflammatory cells, and matrix remodeling. In AAA patients, data revealed different degrees of calcification, inversely correlated with wall stretching and also with inflammation and extracellular matrix degradation. In order to study the role of mechanical stimulation, endothelial cell line (EA.hy926) has been cultured in healthy (10% strain) and pathological (5% strain) dynamic conditions using a bioreactor. In presence of tumor necrosis factor alpha (TNF-α), high levels of matrix metalloproteinase-9 (MMP-9) expression and inflammation are obtained, while mechanical stimulation significantly counteracts the TNF-α effects. Moreover, physiological deformation also plays a significant role in the control of the oxidative stress. Overall our findings indicate that, due to wall calcification, in AAA there is a significant change in terms of decreased wall stretching.