title: Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains.
abstract: Vascular myocytes are central to brain aging. Small vessel disease (SVD; arteriolosclerosis) is a widespread cause of lacunar stroke and vascular dementia and is characterized by fibrosis and depletion of vascular myocytes in small penetrating arteries. Vascular endothelial growth factor (VEGF) is associated with brain aging, and Immunolabeling for vascular endothelial growth factor receptor 2 (VEGFR2) is a potent determinant of cell fate. Here, we tested whether VEGFR2 in vascular myocytes is associated with older age and SVD in human brain. Immunolabeling for VEGFR2 in deep gray matter was assessed in older people with or without moderate-severe SVD or in younger people without brain pathology or with a monogenic form of SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). All cases were without Alzheimer's disease pathology. Myocyte VEGFR2 was associated with increasing age (p = 0.0026) but not with SVD pathology or with sclerotic index or blood vessel density. We conclude that VEGFR2 is consistently expressed in small artery myocytes of older people and may mediate effects of VEGF on brain vascular aging.
authors.affiliation: Stroke and Dementia Research Centre, Cardiac and Cellular Sciences Research Institute, St Georges University of London, London, UK.
authors.forename: Fiyyaz
authors.initials: F
authors.lastname: Ahmed-Jushuf
authors.affiliation: Stroke and Dementia Research Centre, Cardiac and Cellular Sciences Research Institute, St Georges University of London, London, UK.
authors.forename: Nadim S
authors.initials: NS
authors.lastname: Jiwa
authors.affiliation: Stroke and Dementia Research Centre, Cardiac and Cellular Sciences Research Institute, St Georges University of London, London, UK.
authors.forename: Anum S
authors.initials: AS
authors.lastname: Arwani
authors.affiliation: Department of Cellular Pathology, St Georges Healthcare NHS Trust, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Foot
authors.affiliation: Stroke and Dementia Research Centre, Cardiac and Cellular Sciences Research Institute, St Georges University of London, London, UK; Department of Cellular Pathology, St Georges Healthcare NHS Trust, London, UK.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Bridges
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Raj N
authors.initials: RN
authors.lastname: Kalaria
authors.affiliation: OPTIMA and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK; Department of Clinical Neurology, Oxford University, John Radcliffe Hospital, Oxford, UK; Department of Neuropathology, Oxford-Radcliffe NHS Trust, Oxford, UK.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Esiri
authors.affiliation: Stroke and Dementia Research Centre, Cardiac and Cellular Sciences Research Institute, St Georges University of London, London, UK. Electronic address: ahainsworth@sgul.ac.uk.
authors.forename: Atticus H
authors.initials: AH
authors.lastname: Hainsworth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism*; D046589:CADASIL / Q000235:genetics* / Q000378:metabolism*; D002536:Cerebral Arteries / Q000166:cytology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D032342:Muscle Cells / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism*
chemical_list: C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Arteriolosclerosis; Flk-1; Small vessel disease; Vascular dementia; Vasculopathy