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Stroke. 2018 Sep;49(9):2227-2229. doi: 10.1161/STROKEAHA.118.022613.

Circulating Vascular Growth Factors and Magnetic Resonance Imaging Markers of Small Vessel Disease and Atrophy in Middle-Aged Adults.

Raman MR1,2, Himali JJ1,2,3, Conner SC2,3, DeCarli C4, Vasan RS5,2,6, Beiser AS1,2,3, Seshadri S1,2,7,8,9,10, Maillard P4, Satizabal CL1,2,11,10.

Author information

1
From the Department of Neurology (M.R.R., J.J.H., A.S.B., S.S., C.L.S.).
2
Boston University School of Medicine, MA; Framingham Heart Study, MA (M.R.R., J.J.H., S.C.C., R.S.V., A.S.B., S.S., C.L.S.).
3
Department of Biostatistics (J.J.H., S.C.C., A.S.B.).
4
Boston University School of Public Health, MA; Department of Neurology, UC Davis School of Medicine, Sacramento, CA (C.D., P.M.).
5
Department of Medicine (R.S.V.).
6
Department of Epidemiology (R.S.V.).
7
Department of Neurology (S.S.).
8
Department of Psychiatry (S.S.).
9
Department of Cellular and Integrative Physiology (S.S.).
10
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, TX (S.S., C.L.S.).
11
Department of Epidemiology & Biostatistics (C.L.S.).

Abstract

Background and Purpose- Little is known about associations between vascular growth factors and magnetic resonance imaging (MRI) markers in midlife. We investigated the association of serum VEGF (vascular endothelial growth factor), Ang2 (angiopoietin 2), sTie2 (soluble tyrosine kinase with immunoglobulin-like and EGF-like domains 2), and HGF (hepatocyte growth factor) concentrations with MRI markers of brain aging in middle-aged adults. Methods- We evaluated 1853 participants (mean age, 46±9 years; 46% men) from the Framingham Heart Study. Serum growth factor concentrations were measured using standardized immunoassays. Outcomes included total brain, cortical and subcortical gray matter, white matter, cerebrospinal fluid, and white matter hyperintensity volumes derived from MRI; as well as fractional anisotropy in white matter tracts from diffusion tensor imaging. We related VEGF, Ang2, sTie2, and HGF to MRI measures using multivariable regression models adjusting for vascular risk factors. We tested for interactions with APOE (apolipoprotein E) genotype and CRP (C-reactive protein). Results were corrected for multiple comparisons. Results- Higher sTie2 was associated with smaller total brain (estimate by SD unit±SE=-0.08±0.02, P=0.002) and larger white matter hyperintensity (0.08±0.02, P=0.002) volumes. Furthermore, higher Ang2 (0.06±0.02, P=0.049) and HGF (0.09±0.02, P=0.001) were associated with larger cerebrospinal fluid volumes. Finally, higher Ang2 was associated with decreased fractional anisotropy, in APOE-ε4 carriers only. Conclusions- Vascular growth factors are associated with early MRI markers of small vessel disease and neurodegeneration in middle-aged adults.

KEYWORDS:

C-reactive protein; aging; angiogenic proteins; apolipoprotein E4; magnetic resonance imaging

PMID:
30354979
PMCID:
PMC6101979
[Available on 2019-09-01]
DOI:
10.1161/STROKEAHA.118.022613

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