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Comparative Study
. 2010 May;72(4):376-82.
doi: 10.1097/PSY.0b013e3181d74c48. Epub 2010 Apr 5.

Oxytocin attenuates atherosclerosis and adipose tissue inflammation in socially isolated ApoE-/- mice

Daniel A Nation  1 , Angela Szeto, Armando J Mendez, Larry G Brooks, Julia Zaias, Edward E Herderick, Julie Gonzales, Crystal M Noller, Neil Schneiderman, Philip M McCabe
Affiliations
Comparative Study

Oxytocin attenuates atherosclerosis and adipose tissue inflammation in socially isolated ApoE-/- mice

Daniel A Nation et al. Psychosom Med. 2010 May.

Abstract

Objective: To determine the effect of exogenous oxytocin (OT) administration on inflammation and atherosclerosis in socially isolated apoE(-/-) mice. Hyperlipidemic animals housed in isolated or stressful social environments display more extensive atherosclerosis than those in an affiliative social environment. The neurohypophyseal peptide OT may be involved in both affiliative social behavior and cardiovascular homeostasis, suggesting a role in mediating the benefits of positive social interactions on atherosclerosis.

Methods: A total of 43, 12-week-old, apoE(-/-) mice were surgically implanted with osmotic minipumps containing OT (n = 23) or vehicle (n = 20). Blood samples were taken at baseline and after 6 weeks and 12 weeks of treatment. After 12 weeks of treatment, animals were killed, and samples of adipose tissue were dissected from a subset of OT-treated (n = 12) and vehicle-treated (n = 12) animals and incubated in culture media for 6 hours. Media samples were analyzed for interleukin (IL)-6 concentration corrected by sample dry weight. Aortas were dissected, formalin-fixed, and stained with oil-red O for en face quantification of lesion area. t tests were used to compare group means on measures of percent lesion area and IL-6 concentrations.

Results: There were no group differences in plasma lipids. Adipose tissue samples taken from OT-treated animals secreted significantly less IL-6 over 6 hours (p < .01). OT-treated animals displayed significantly less atherosclerosis in the thoracic aorta (p < .05).

Conclusions: These results indicate that peripheral OT administration can inhibit atherosclerotic lesion development and adipose tissue inflammation, suggesting a potential role for this neuropeptide in mediating the benefits of stable group housing on atherosclerosis.

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Figures

Figure 1
Figure 1
Tail-cuff blood pressure measured in awake C57BL/6 pilot mice. Baseline blood pressure from mice was taken 1 day before surgical osmotic minipump implantation and 10 days, 12 days, and 14 days postsurgical pump implantation. Mice with osmotic minipumps containing vehicle showed no differences in systolic and diastolic blood pressure, and data were pooled. There were no observable differences for systolic and diastolic measurements after surgery between the two groups (n = 2/group). Data represent mean and standard error values.
Figure 2
Figure 2
Extent of atherosclerosis in control and oxytocin-treated apoE−/− mice. A) Lesion prevalence maps display the cumulative aortic area covered by atherosclerotic lesions, as indicated by oil-red-O staining, with darker areas representing greater lesion frequency in a given location. Visual inspection of prevalence maps revealed that nearly all of the disease occurred in the aortic arch and the thoracic aorta (circled regions), with an apparent difference in lesion prevalence between groups within the thoracic region (arrows). Quantitative analysis of aortic percent lesion area within the thoracic aorta (B) and the aortic arch (C) confirmed the significant group difference in the thoracic aorta. Data represent mean and standard error values.
Figure 3
Figure 3
Analysis of interleukin (IL)-6 secretion from visceral adipose tissue samples over 6 hours of ex vivo incubation, revealing that samples taken from oxytocin-treated animals produced less IL-6 than those of the vehicle control group. Values are expressed as picograms IL-6 per gram of sample dry weight. Data represent mean and standard error values.
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