Abstract P62: Older Adults With Cerebral Small Vessel Disease Show Increased Levels of Circulating Vascular Endothelial Growth Factor D

Abstract

Introduction: Cerebral small vessel disease (SVD) resulting from pathological changes in cerebral microvessels is a common precursor of stroke and dementia. Progressive and insidious damage to the cerebral microvasculature may trigger angiogenic processes to promote vessel repair. However, few previous studies have explored the angiogenic response to SVD. In a cohort of older adults with early evidence of SVD, we aimed to examine circulating levels of vascular endothelial growth factor D (VEGF-D)—a secreted glycoprotein with high angiogenic and lymphangiogenic potential—which has previously been linked to heart failure, atrial fibrillation, and ischemic stroke. Methods: Sixty independently living older adults (mean age = 69.7 years; SD = 7.5; age range 55-90 years; 38.3% male) free of dementia or clinical stroke were recruited from the community and underwent venipuncture and brain MRI. Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, Flt-1). MRI changes thought to represent microvascular pathologies (white matter hyperintensities, microbleeds and lacunes) were evaluated and total SVD load was determined using a previously validated score. Multiple linear regression examined the relationship between circulating proangiogenic proteins levels and total SVD load. Results: Moderate/severe white matter hyperintensity burden was identified by Fazekas scale in 40.0% of participants, small lacunes were identified in 13.3% and microbleeds in 6.7%. Simple linear regression revealed a positive relationship between circulating VEGF-D and total SVD score (p = .019), which remained significant in multiple regression controlling for age, sex and Framingham stroke score (p = .017). VEGF-D was significantly positively correlated with VEGF-C (r = .37), Flt-1 (r = .31) and Tie-2 (r = .42). Conclusions: These findings suggest that elevated levels of circulating VEGF-D correspond with greater damage to the cerebral microvasculature in older adults with no history of clinical stroke or dementia. Additional studies are warranted to determine whether activation of systemic proangiogenic growth factors represents an early attempt to rescue the vascular endothelium and repair damage in cerebral SVD.