Hydroxy-oleic acid, but not oleic acid, inhibits pharmacologic vascular responsiveness in isolated aortic tissue
Bass, V., S. Snow, U. Kodavanti, AND M. Madden. Hydroxy-oleic acid, but not oleic acid, inhibits pharmacologic vascular responsiveness in isolated aortic tissue. Society of Toxicology Annual Meeting, Baltimore, MD, March 12 - 16, 2017.
These findings demonstrate that oxidized oleic acid, but not the parent fatty acid, either from endogenous biological sources or from air pollution, induced vascular physiological changes in an in vitro model. These observations have mechanistic and intervention implications for the assigning a role for chemical components in diesel exhaust which are known to alter human vascular reactivity in vivo.
Oleic acid (OA) and other fatty acids can become abundant in the systemic circulation after air pollution exposure as endogenously released lipolysis byproducts or by entering the body as a component of air pollution. Vascular damage has been observed with OA infusion, but it is not yet established whether increased circulating OA is able to produce the type of adverse cardiovascular effects associated with exposure to air pollution, or the mechanisms involved with such damage. Based on responses observed upon exposure of cultured endothelial cells, we hypothesized that OA and a hydroxylated metabolite (12-OH OA) would increase vascular tissue injury and impair vascular reactivity. Thoracic descending aorta tissue was collected from male Wistar Kyoto rats, aged 13-16 weeks. Prior to reactivity testing, independent LDH assays were performed with aortic rings to establish a subcytotoxic OA dose. To determine changes in vascular reactivity, aortic ring segments (n=3-4) were exposed for 1 hr to 100 µM OA, 12-OH OA, or an equivalent EtOH vehicle, followed by testing using myography and pharmacologic agents. Only 12-OH OA exposure significantly inhibited acetylcholine-induced endothelium-dependent vasorelaxation in aortic ring segments (25-30% reduction relative to EtOH control), based on maximum relaxation and dose-response. No change was seen in smooth muscle sensitivity to an exogenous nitric oxide source, sodium nitroprusside. Maximum aortic contractile force generated in response to 10 µM phenylephrine was reduced by 25% in the 12-OH OA group compared to the EtOH group, despite no difference in maximum force response when tested with KCl. Collectively, these data indicate that at non-cytotoxic exposures, 12-OH OA impairs endothelium-dependent relaxation, while its parent compound does not, suggesting that metabolism or conversion of OA may be required to produce vascular effects. Hydroxylated fatty acid products may play a role in the vascular responses observed upon air pollution exposure. (Does not reflect official US EPA policy).
Record Details:Record Type: DOCUMENT (PRESENTATION/POSTER)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CLINICAL RESEARCH BRANCH