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Effects of Acute and Chronic Biomechanical Strain on Human Cerebral Endothelial Cells in Altering their Proteome Profile

[ Vol. 14 , Issue. 3 ]

Author(s):

Nurul Farhana Jufri, Abidali Mohamedali, Seong Beom Ahn, Alberto Avolio and Mark Scott Baker*   Pages 214 - 223 ( 10 )

Abstract:


Objectives: Hypertension exerts a chronic tensile stretch on the endothelial lining of the inner layer of blood vessels and is thought to cause cellular injury leading to numerous pathologies. Studies have indicated that tensile stretch could alter the phenotype and cellular functions of the cell, depending on the stretch magnitude applied. However, the molecular mechanisms of the cellular injury under these conditions remain unclear.

Method: In order to investigate the protein changes potentially involved in hypertension, human cerebral microvascular endothelial cells were subjected to a simulated physiological (5%) and pathological (20%) cyclic stretch for a period of 2 hr or 18 hr on fibronectin-coated silicone cubes followed by a quantitative label-free proteomics experiment on cell lysates.

Result: Data analysis demonstrated that proteins involved in structural activity were significantly up-regulated in the 20% condition at 2 hrs notably microtubule actin cross-linking factor 1 [MACF1 (+24.6 fold)] and tubulin alpha chain 3 [TUBAL3 (+8.0 fold)]. Similarly, proteins that have been previously observed to be altered in clinical aneurysm formation such as titin [TTN (+60.4)] and apolipoprotein B-100 [APOB (+21.3 fold)]) were also found to be up-regulated at 20% stretch for 18 hrs. Protein interaction network analysis suggested that the signaling pathway involving nuclear factor-kappa B (NFkB) may the main protein network affected by shorter stretch conditions. Compensatory inflammatory processes may have commenced during early exposure to stretch.

Conclusion: This study provides a basis for understanding early and long-term molecular changes that may lead to vascular dysfunction as a consequence of pathological stretch.

Keywords:

Blood pressure, cyclic stretch, endothelial cell, hypertension, proteomics, vascular system.

Affiliation:

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, New South Wales, 2109, Department of Chemistry and Biomolecular Sciences, Faculty of Science, Macquarie University, New South Wales, 2109, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, New South Wales, 2109, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, New South Wales, 2109, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, New South Wales, 2109

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