Purpose: The present study investigates the potential anti-inflammatory effects of in vivo oxytocin (OT) infusion on adipose tissue inflammation in the Watanabe Heritable Hyperlipidimic Rabbits (WHHL). Methods: Twenty-eight 3-month-old WHHL were surgically implanted with osmotic minipumps containing OT (n = 14, infusion rate 250 ng/kg/hr) or vehicle (n = 14). Blood samples were taken at baseline, midpoint, and endpoint for lipids and C-reactive protein (CRP). After 16 weeks, animals were sacrificed and samples of adipose tissue (epididiymal, retroperitoneal, mesenteric, pericardial, and subcutanous) were collected and analyzed for pro-inflammatory cytokine (IL-6, TNF-α, and MCP-1) and anti- inflammatory adipokine (adiponectin and IL-10) expression levels by Real Time- Polymerase Chain Reaction. Adipose tissue was also immunohistologically analyzed for macrophage infiltration. Aortas were dissected, formalin-fixed, and stained with oil-red O for en face quantification of lesion area. Student’s t-tests were used to compare group means for all measures. Results: Endpoint OT levels were significantly different (p < .05) between the control ( M = 11.28 pg/ml, SEM = 2.5) and treatment group (M = 132.35 pg/ml, SEM = 8.5). Plasma lipids were not altered by OT infusion. OT-treatment significantly decreased plasma CRP, a marker of systemic inflammation, at midpoint and endpoint compared to controls (p = 0.05). OT-treated animals displayed significantly less atherosclerosis in the thoracic aorta (p < 0.05); a finding similar to our previously published study in a mouse model of atherosclerosis. In some fat depots, there was a trend suggesting adiponectin gene expression increased in the OT-treatment group. There were no significant differences or trends regarding macrophage infiltration in adipose tissue. Conclusions: Oxytocin infusion attenuated thoracic aortic atherosclerosis, plasma CRP, and may affect inflammatory cytokine expression in adipose tissue in the WHHL model.

INTRODUCTION: Platelets are involved in the inflammatory and thrombotic complications associated with atherosclerosis. Human neutrophil peptides (HNP), released from activated neutrophils, demonstrate inflammatory effects related to lesion development. HNP bind the low-density lipoprotein receptor (LR) family member LRP1 and LRP8 is the only member on platelets. HYPOTHESIS: HNP enhance platelet activation and aggregation through interactions with LRP8. METHODS: Platelet activation and aggregation in response to HNP were determined using flow cytometry and aggregometry. Activation was also examined in the presence of recombinant LRP8 and in LRP8 knockout platelets. RESULTS: HNP activate platelets as determined by P-selectin expression and the formation of microparticles. HNP sensitize platelets enhancing their aggregatory response to ADP. Lastly, LRP8 plays a role in HNP-induced platelet activation. CONCLUSIONS: With an improved understanding of the mechanism by which HNP induce platelet activation, we may be able to devise therapeutic strategies to treat patients with cardiovascular diseases.

INTRODUCTION: Platelets are involved in the inflammatory and thrombotic complications associated with atherosclerosis. Human neutrophil peptides (HNP), released from activated neutrophils, demonstrate inflammatory effects related to lesion development. HNP bind the low-density lipoprotein receptor (LR) family member LRP1 and LRP8 is the only member on platelets. HYPOTHESIS: HNP enhance platelet activation and aggregation through interactions with LRP8. METHODS: Platelet activation and aggregation in response to HNP were determined using flow cytometry and aggregometry. Activation was also examined in the presence of recombinant LRP8 and in LRP8 knockout platelets. RESULTS: HNP activate platelets as determined by P-selectin expression and the formation of microparticles. HNP sensitize platelets enhancing their aggregatory response to ADP. Lastly, LRP8 plays a role in HNP-induced platelet activation. CONCLUSIONS: With an improved understanding of the mechanism by which HNP induce platelet activation, we may be able to devise therapeutic strategies to treat patients with cardiovascular diseases.

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OBJECTIVE—Absence of stearoyl-CoA desaturase-1 (SCD1) in mice reduces plasma triglycerides and provides protection from obesity and insulin resistance, which would be predicted to be associated with reduced susceptibility to atherosclerosis. The aim of this study was to determine the effect of SCD1 deficiency on atherosclerosis. Methods and RESULTS—Despite an antiatherogenic metabolic profile, SCD1 deficiency increases atherosclerosis in hyperlipidemic low density lipoprotein receptor (LDLR)-deficient mice challenged with a western diet. Lesion area at the aortic root is significantly increased in males and females in two models of SCD1 deficiency. Inflammatory changes are evident in the skin of these mice, including increased intercellular adhesion molecule (ICAM)-1 and ulcerative dermatitis. Increases in ICAM-1 and interleukin-6 are also evident in plasma of SCD1-deficient mice. HDL particles demonstrate changes associated with inflammation, including, decreased plasma apoA-II and apoA-I and paraoxonase-1 and increased plasma serum amyloid A. Lipopolysaccharide-induced inflammatory response and cholesterol efflux are not altered in SCD1-deficient macrophages. In addition, when SCD1 deficiency is limited to bone-marrow derived cells, lesion size is not altered in LDLR-deficient mice. CONCLUSIONS—These studies reinforce the crucial role of chronic inflammation in promoting atherosclerosis, even in the presence of antiatherogenic biochemical and metabolic characteristics. [The original version of this article, along with updated information and services is located on the World Wide Web at: http://atvb.ahajournals.org/cgi/content/full/29/3/341] [UBC users: please click on the UBC eLink icon at the bottom of this record]

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