Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 37, Issue 7, Pages 2614-2625Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X16672482
Keywords
Blood-brain barrier; capillaries; cerebrovascular disease; hemodynamics; microcirculation; neurovascular unit; vascular biology
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Funding
- Spain Ministerio de Economia y Competitividad [SAF2013-43302-R]
- NIH [R01 GM 49039]
- Spain's Ministry of Health (Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (FEDER) [RD12/0042/0020]
- Fundacio Empreses IQS
- Banco Santander fellowship programs
- IQS School of Engineering
- Beatriu de Pinos Program, Modalitat-A - AGAUR [2013 BP_A 00051]
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Microvascular endothelial cells at the blood-brain barrier exhibit a protective phenotype, which is highly induced by biochemical and biomechanical stimuli. Amongst them, shear stress enhances junctional tightness and limits transport at capillary-like levels. Abnormal flow patterns can reduce functional features of macrovascular endothelium. We now examine if this is true in brain microvascular endothelial cells. We suggest in this paper a complex response of endothelial cells to aberrant forces under different flow domains. Human brain microvascular endothelial cells were exposed to physiological or abnormal flow patterns. Physiologic shear (10-20dyn/cm(2)) upregulates expression of tight junction markers Zona Occludens 1 (1.7-fold) and Claudin-5 (more than 2-fold). High shear stress (40dyn/cm(2)) and/or pulsatility decreased their expression to basal levels and altered junctional morphology. We exposed cells to pathological shear stress patterns followed by capillary-like conditions. Results showed reversible recovery on the expression of tight junction markers. Flow protection of barrier phenotype commensurate with junctional signaling pathways decrease (Src, 0.25-fold, ERK, 0.77-fold) when compared to static conditions. This decrease was lost under high shear and pulsatile flow. In conclusion, abnormal shear stress inherent to systemic vascular disease leads to barrier impairment, which could be reverted by hemodynamic interventions.
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