Deletion of L-Selectin Increases Atherosclerosis Development in ApoE−/− Mice

PLoS One

Pavani Mocharla¹  Izabela Rozenberg¹  Pierre Rotzius¹  Felix C. Tanner¹  Thomas F. Lüscher¹  Anders Hallenberg²  Susanna H. M. Sluka²  Jan Borén²  Einar E. Eriksson²  Nicolle Kränkel³  Ulf Landmesser³  Lubor Borsig⁴ 

[1] Cardiovascular Research, Institute of Physiology, University of Zurich, Zurich, Switzerland;Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland;Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden;Wallenberg Laboratory, Sahlgrenska Academy at Göteborg University, Goteborg, Sweden

关键词: White blood cells;    Atherosclerosis;    Aorta;    Lymphocytes;    Cytokines;    Blood plasma;    Diet;    Endothelium;   

DOI  :  10.1371/journal.pone.0021675

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Atherosclerosis is an inflammatory disease characterized by accumulation of leukocytes in the arterial intima. Members of the selectin family of adhesion molecules are important mediators of leukocyte extravasation. However, it is unclear whether L-selectin (L-sel) is involved in the pathogenesis of atherosclerosis. In the present study, mice deficient in L-selectin (L-sel−/−) animals were crossed with mice lacking Apolipoprotein E (ApoE−/−). The development of atherosclerosis was analyzed in double-knockout ApoE/L-sel (ApoE−/− L-sel−/−) mice and the corresponding ApoE−/− controls fed either a normal or a high cholesterol diet (HCD). After 6 weeks of HCD, aortic lesions were increased two-fold in ApoE−/− L-sel−/− mice as compared to ApoE−/− controls (2.46%±0.54% vs 1.28%±0.24% of total aortic area; p<0.05). Formation of atherosclerotic lesions was also enhanced in 6-month-old ApoE−/− L-sel−/− animals fed a normal diet (10.45%±2.58% vs 1.87%±0.37%; p<0.05). In contrast, after 12 weeks of HCD, there was no difference in atheroma formation between ApoE−/− L-sel−/− and ApoE−/− mice. Serum cholesterol levels remained unchanged by L-sel deletion. Atherosclerotic plaques did not exhibit any differences in cellular composition assessed by immunohistochemistry for CD68, CD3, CD4, and CD8 in ApoE−/− L-sel−/− as compared to ApoE−/− mice. Leukocyte rolling on lesions in the aorta was similar in ApoE−/− L-sel−/− and ApoE−/− animals. ApoE−/− L-sel−/− mice exhibited reduced size and cellularity of peripheral lymph nodes, increased size of spleen, and increased number of peripheral lymphocytes as compared to ApoE−/− controls. These data indicate that L-sel does not promote atherosclerotic lesion formation and suggest that it rather protects from early atherosclerosis.

【 授权许可】

CC BY