Cheryl Wellington, Canada
University of British Columbia Pathology and Laboratory MedicinePresenter of 5 Presentations
LIVE DISCUSSION
LIVE GENERAL DISCUSSION
- Todd Golde, United States of America
- Darren J. Baker, United States of America
- Dorota Skowronska-Krawczyk, United States of America
- Joao Pedro De Magalhães, United Kingdom
- Mike Sapieha, Canada
- Guojun Bu, United States of America
- Rik Ossenkoppele, Netherlands
- Thomas Montine, United States of America
- Steven Barnes, United States of America
- Adriana Di Polo, Canada
- Cheryl Wellington, Canada
- Berislav V. Zlokovic, United States of America
- Luis Alarcon-Martinez, Canada
- Anusha Mishra, United States of America
- Randy Kardon, United States of America
LIVE DISCUSSION & Q&A: WHY ARE THE VASCULAR COMPONENTS AND BLOOD-BRAIN/BLOOD-RETINA BARRIERS OF THE BRAIN AND EYE IMPORTANT CONTRIBUTORS TO THE TIPPING POINT BETWEEN HEALTH AND DISEASE?
BIOENGINEERED VASCULAR MODELS FOR DEMENTIA (INVOLVING ENDOTHELIA, SMOOTH MUSCLE, AND ASTROCYTES)
THE ROLE OF HIGH DENSITY LIPOPROTEINS IN THE VASCULAR CONTRIBUTIONS TO ALZHEIMER’S DISEASE
Abstract
Aims
To determine the physiological functions of human high-density lipoprotein (HDL) particles on human endothelial cells cultured alone or in context with other cells of the neurovascular unit.
Abstract Body
Aims: To determine the physiological functions of human high-density lipoprotein (HDL) particles on human endothelial cells cultured alone or in context with other cells of the neurovascular unit.
Methods: We used primary and human iPSC cells in standard monoculture and in a 3-dimensional bioengineered arterial model of the perfused human cerebrovasculature to study cerebral amyloid angiopathy (CAA) as measured by Aβ deposition and transport, and Aβ-induced endothelial inflammation measured by monocyte binding.
Results: HDL vascular Aβ accumulation independently of its principal binding protein, scavenger receptor (SR)-BI, in contrast to the SR-BI-dependent mechanism by which HDL prevents Aβ-induced vascular inflammation. HDL also reduces CAA through four mechanisms: i) altering Aβ binding to collagen-I, ii) forming a complex with Aβ that maintains its solubility, iii) diminishing collagen-I expression by smooth-muscle cells (SMC), and iv) attenuating Aβ uptake in SMC perhaps by reducing LRP1 expression. Finally, HDL particles enriched in apolipoprotein (apo)E appear to be the major drivers of these effects.
Conclusions: Circulating HDL, particularly HDL particles with apoE, may have beneficial effects on the cerebrovasculature, acting from the lumen to facilitate Ab egress from the brain and reduce cerebrovascular inflammation.
Methods
We used primary and human iPSC cells in standard monoculture and in a 3-dimensional bioengineered arterial model of the perfused human cerebrovasculature to study cerebral amyloid angiopathy (CAA) as measured by Aβ deposition and transport, and Aβ-induced endothelial inflammation measured by monocyte binding.
Results
HDL vascular Aβ accumulation independently of its principal binding protein, scavenger receptor (SR)-BI, in contrast to the SR-BI-dependent mechanism by which HDL prevents Aβ-induced vascular inflammation. HDL also reduces CAA through four mechanisms: i) altering Aβ binding to collagen-I, ii) forming a complex with Aβ that maintains its solubility, iii) diminishing collagen-I expression by smooth-muscle cells (SMC), and iv) attenuating Aβ uptake in SMC perhaps by reducing LRP1 expression. Finally, HDL particles enriched in apolipoprotein (apo)E appear to be the major drivers of these effects.
Conclusions
Circulating HDL, particularly HDL particles with apoE, may have beneficial effects on the cerebrovasculature, acting from the lumen to facilitate Aβ egress from the brain and reduce cerebrovascular inflammation.