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
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.