Endothelium-dependent contractions induced by aging and diet-induced obesity are attenuated in lipocalin-2 deficient mice

Abstract

AIM: Levels of Lipocalin-2, a pro-inflammatory adipokine, correlates with adiposity, dyslipidemia, hyperglycemia and insulin resistance. The present study evaluates vascular function in mice with deletion of the lipocalin-2 gene (Lcn2-KO). METHODS: Wild type (WT) and Lcn2-KO mice were fed with standard or high fat diet for 3–17 weeks. Intra-arterial blood pressure was measured. Isometric tension was measured in carotid artery rings with or without endothelium. Protein expression was measured by Western blotting. RESULTS: The obesity-induced increase in systolic blood pressure was attenuated in Lcn2-KO mice. In aged or obese WT mice, acetylcholine (ACh)-elicited endothelium-dependent contractions were abolished by the COX-1 selective inhibitor SC560 and the NADH oxidase inhibitor diphenylene iodonium. These contractions were attenuated in Lcn2-KO mice. ACh-stimulated superoxide anion production, COX-1 mRNA and protein expression were decreased in Lcn2-KO arteries. ACh-induced production of prostacyclins (PGI2) was lower in Lcn2-KO preparations. In aged or obese WT mice, PGI2 caused contractions in rings without endothelium but these contractions were reversed to relaxations in Lcn2-KO arteries. CONCLUSIONS: Lipocalin-2 plays an important role in obesity-induced hypertension and endothelial dysfunction through production of superoxide anions and COX-1 expression.