Effect of Cyclic Stretch on Vascular Endothelial Cells and Abdominal Aortic Aneurysm (AAA): Role in the Inflammatory Response.
Martina RamellaGiulia BertozziLuca FusaroMaria TalmonMarcello ManfrediMarta Calvo CatoriaFrancesco CasellaCarla Maria PortaRenzo BoldoriniLuigia Grazia FresuEmilio MarengoFrancesca BoccafoschiPublished in: International journal of molecular sciences (2019)
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 in vitro 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.
Keyphrases
- endothelial cells
- abdominal aortic aneurysm
- oxidative stress
- inflammatory response
- extracellular matrix
- rheumatoid arthritis
- chronic kidney disease
- end stage renal disease
- induced apoptosis
- high glucose
- poor prognosis
- ejection fraction
- newly diagnosed
- lipopolysaccharide induced
- vascular endothelial growth factor
- coronary artery
- prognostic factors
- wastewater treatment
- dna methylation
- ischemia reperfusion injury
- big data
- long non coding rna
- machine learning
- data analysis
- binding protein
- artificial intelligence
- risk assessment
- deep learning
- pulmonary arterial hypertension