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

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 immunoglo...

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Bibliographic Details
Published in:Stroke (1970) Vol. 49; no. 9; p. 2227
Main Authors: Raman, Mekala R, Himali, Jayandra J, Conner, Sarah C, DeCarli, Charles, Vasan, Ramachandran S, Beiser, Alexa S, Seshadri, Sudha, Maillard, Pauline, Satizabal, Claudia L
Format: Journal Article
Language:English
Published: United States 01.09.2018
Subjects:
Adult
Aging - blood
Anisotropy
Apolipoproteins E - genetics
Atrophy
Brain - diagnostic imaging
Brain - pathology
C-Reactive Protein - metabolism
Cerebral Small Vessel Diseases - blood
Cerebral Small Vessel Diseases - diagnostic imaging
Diffusion Tensor Imaging
Female
Gray Matter - diagnostic imaging
Gray Matter - pathology
Hepatocyte Growth Factor - blood
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Male
Middle Aged
Organ Size
Receptor, TIE-2 - blood
Vascular Endothelial Growth Factor A - blood
Vesicular Transport Proteins - blood
White Matter - diagnostic imaging
White Matter - pathology
magnetic resonance imaging
C-reactive protein
aging
apolipoprotein E4
angiogenic proteins
ISSN:1524-4628, 1524-4628
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Summary: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.
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ISSN:1524-4628
1524-4628
DOI:10.1161/STROKEAHA.118.022613