Recent studies have provided evidence of the relevance of pulsatility and hypertension in the following areas: (i) pressure and flow pulsatility and regulation of cerebral blood flow, (ii) cerebral and systemic haemodynamics, hypertension and brain pathologies (cognitive impairment, dementia, Alzheimer's disease), (iii) stroke and cerebral small vessel disease, (iv) cerebral haemodynamics and noninvasive estimation of cerebral vascular impedance, (v) cerebral and systemic pulsatile haemodynamics and intracranial pressure, (iv) response of brain endothelial cells to cyclic mechanical stretch and increase in amyloid burden. Studies to date, producing increasing epidemiological, clinical and experimental evidence, suggest a potentially significant role of systemic haemodynamic pulsatility on structure and function of the brain.
Amyloid β (Aβ) deposition is a hallmark of Alzheimer’s disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, β-secretase 1, eventuating increased-Aβ generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aβ levels.
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