Advances in endothelial shear stress proteomics

Abstract

The vascular endothelium lining the luminal surface of all blood vessels is constantly exposed to shear stress exerted by the flowing blood. Blood flow with high laminar shear stress confers protection by activation of antiatherogenic, antithrombotic and anti-inflammatory proteins, whereas low or oscillatory shear stress may promote endothelial dysfunction, thereby contributing to cardiovascular disease. Despite the usefulness of proteomic techniques in medical research, however, there are relatively few reports on proteome analysis of cultured vascular endothelial cells employing conditions that mimic in vivo shear stress attributes. This review focuses on the proteome studies that have utilized cultured endothelial cells to identify molecular mediators of shear stress and the roles they play in the regulation of endothelial function, and their ensuing effect on vascular function in general. It provides an overview on current strategies in shear stress-related proteomics and the key proteins mediating its effects which have been characterized so far.

Keywords::

• endothelial dysfunction
• mass spectrometry
• proteomics
• shear stress

Acknowledgements

The authors acknowledge support by the German Research Foundation (DFG) and the Open Access Publication Fund of the University of Göttingen. S Firasat is the recipient of a German Academic Exchange Service (DAAD) award.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Characteristic changes in blood flow are critical to vascular disease development and progression.

• Endothelial cells (ECs) from different vascular sites are heterogeneous with respect to their physical and physiological characteristics.

• Laminar shear stress and cyclic stretch generated by pulsatile blood flow are important mechanical forces that modulate endothelial function.

• Loss of laminar shear stress is far more important than the relatively small increase in oscillatory shear stress to provoke a proatherosclerotic phenotype.

• For implications of hemodynamic forces with reference to a particular cardiovascular complication a relevant laboratory model should be chosen.

• Cell coculture studies are mandatory to accurately reflect the pathogenesis caused by altered hemodynamics, namely, in the context of endothelial dysfunction.

• Differential proteome analysis of laminar and oscillating shear stress could provide further insights into conversion of functional phenotype of ECs to dysfunctional.

• Improved in vitro devices to mimic pulsating fluid movement of the human vascular system are still wanted to explore endothelial physiology.

• Proteomic investigations of vascular ECs in connection to clinical presentation are central to precisely detect novel disease and therapeutic biomarkers.