Abstract 18245: Palmitic Acid-induced Endothelial Dysfunction in Human Leptomeningeal and Adipose Arterioles
Introduction: Epidemiologic data show strong link between cardiovascular risk factors and dementia-related illnesses (DRI) such as Alzheimer’s disease (AD) with evidence that the earliest changes in AD involve vascular dysfunction. The mechanisms behind vascular impairment in DRI remain poorly understood, and lack of a human model to study them impedes progress towards a cure.
Aim: The aim of the study is to determine the effects of acute exposure to palmitic acid (PA), a saturated fatty acid implicated in atherosclerosis, on endothelium-dependent and smooth muscle dependent function in human leptomeningeal arterioles (LMA) and peripheral adipose tissue arterioles (AA).
Methods: LMA from cadavers of brain donors (post-mortem interval 3.3±0.4 hours; 2 with mild cognitive impairment, 1 Parkinson's disease, 1 Lewy body dementia) and abdominal subcutaneous AA from living subjects with no vascular disease undergoing routine surgery were isolated, cannulated and pressurized. Following preconstriction with endothelin-1, baseline (control) dilation response to acetylcholine and papaverine was measured. Arterioles were then exposed to 1 hour of PA (150 μM) and a second dilation response was measured.
Results: (see Figure) PA decreased dilator response to acetylcholine in both LMA and AA (PA-induced change in dilator response to acetylcholine 10-4M: -28.1±6.8 % for LMA and -33.8±7.4% for AA, both p<0.05 versus baseline control). There was no significant reduction in dilator response to papaverine. The changes in dilator response with PA versus control were not different between LMA and AA.
Conclusions: Acute exposure to PA induced endothelial dysfunction in human leptomeningeal arterioles suggesting a potential mechanism for vascular dysfunction that could contribute to AD. Similarity in response to saturated fatty acid between LMA and AA suggests that AA, which is easier to obtain, may be a novel surrogate human model to study brain microvascular function.
Author Disclosures: S. Truran: None. N. Karamanova: None. G. Serrano: None. D. Franco: None. C. Burciu: None. T. Beach: Research Grant; Significant; NIH/NIA/NINDS. A. Roher: None. R.Q. Migrino: Research Grant; Significant; NIH/NIA R21, VA BLRD Merit.
- © 2015 by American Heart Association, Inc.