Leukocyte cell-derived chemotaxin 2 inhibits development of atherosclerosis in mice

Wen-Ming He; Ting Dai; Jiong Chen; Jian-An Wang

doi:10.24272/j.issn.2095-8137.2019.030

Volume 40 Issue 4

Jul. 2019

Turn off MathJax

Article Contents

Article Navigation > Zoological Research > 2019 > 40(4): 317-323

Wen-Ming He, Ting Dai, Jiong Chen, Jian-An Wang. Leukocyte cell-derived chemotaxin 2 inhibits development of atherosclerosis in mice. Zoological Research, 2019, 40(4): 317-323. doi: 10.24272/j.issn.2095-8137.2019.030

Citation:

Wen-Ming He, Ting Dai, Jiong Chen, Jian-An Wang. Leukocyte cell-derived chemotaxin 2 inhibits development of atherosclerosis in mice. Zoological Research, 2019, 40(4): 317-323. doi: 10.24272/j.issn.2095-8137.2019.030

Citation:

PDF( 11040 KB)

Leukocyte cell-derived chemotaxin 2 inhibits development of atherosclerosis in mice

doi: 10.24272/j.issn.2095-8137.2019.030

1.
Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou Zhejiang 310009, China
2.
Department of Cardiology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo Zhejiang 315010, China
3.
Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Meishan Campus, Ningbo University, Ningbo Zhejiang 315832, China

Funds: This project was supported by the Program for the National Natural Science Foundation of China (31772876), Ningbo Municipal Bureau of Science and Technology (2018A610389), Scientific Innovation Team Project of Ningbo (2015C110018), and K.C. Wong Magna Fund in Ningbo University

More Information

Corresponding author: Jiong Chen,Jian-An Wang
Received Date: 2019-04-01
Publish Date: 2019-07-18

Abstract

Abstract

Leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional hepatokine, is involved in many pathological conditions. However, its role in atherosclerosis remains undefined. In this study, we administered vehicle or LECT2 to male Apoe^-/- mice fed a Western diet for 15 weeks. Atherosclerotic lesions were visualized and quantified with Oil-red O and hematoxylin staining. The mRNA expression levels of MCP-1, MMP-1, IL-8, IL-1β, and TNF-α were analyzed by quantitative real-time polymerase chain reaction. Serum TNF-α, IL-1β, IL-8, MCP-1, and MMP-1 concentrations were measured by enzyme-linked immunosorbent assay. CD68, CD31, and α-SMA, markers of macrophages, endothelial cells, and smooth muscle cells, respectively, were detected by immunostaining. Results showed that LECT2 reduced total cholesterol and low-density lipoprotein concentrations in serum and inhibited the development of atherosclerotic lesions, accompanied by reductions in inflammatory cytokines and lower MCP-1, MMP-1, TNF-α, IL-8, and IL-1β mRNA abundance. Furthermore, LECT2 decreased CD68, but increased α-SMA in atherosclerotic lesions, suggesting an increase in smooth muscle cells and reduction in macrophages. In summary, LECT2 inhibited the development of atherosclerosis in mice, accompanied by reduced serum total cholesterol concentration and lower inflammatory responses.
- Leukocyte cell-derived chemotaxin 2 (LECT2),
- Atherosclerosis,
- Inflammation

FullText(HTML)

References(1)

References

[1]

null	Allahverdian S , Chaabane C , Boukais K , Francis GA , Bochaton-Piallat ML . 2018. Smooth muscle cell fate and plasticity in atherosclerosis. Cardiovascular Research, 114(4): 540–550.
null	Boyle JJ , Weissberg PL , Bennett MR . 2003. Tumor necrosis factor-alpha promotes macrophage-induced vascular smooth muscle cell apoptosis by direct and autocrine mechanisms. Arteriosclerosis, Thrombosis, and Vascular Biology, 23(9): 1553–1558.
null	Charo IF , Taubman MB . 2004. Chemokines in the pathogenesis of vascular disease. Circulation Research, 95(9): 858–866.
null	Chistiakov DA , Orekhov AN, Bobryshev YV . 2015. Vascular smooth muscle cell in atherosclerosis. Acta Physiologica, 214(1): 33–50.
null	Daugherty A , Tall AR , MJAP Daemen , Falk E , Fisher EA , Garcia-Cardena G , Lusis AJ , Owens P , III, Rosenfeld ME , Virmani R . 2017. Recommendation on design, execution, and reporting of animal atherosclerosis studies: A scientific statement from the american heart association. Arteriosclerosis, Thrombosis, And Vascular Biology, 37(9): E131–E157.
null	Engelking LJ , Cantoria MJ , Xu Y , Liang G . 2018. Developmental and extrahepatic physiological functions of SREBP pathway genes in mice. Seminars in Cell & Developmental Biology, 81: 98–109.
null	Ference BA, Ginsberg HN , Graham I , Ray KK , Packard CJ , Bruckert E , Hegele RA , Krauss RM , Raal FJ , Schunkert H , Watts GF , Borén J , Fazio S , Horton JD , Masana L , Nicholls SJ , Nordestgaard BG , van de Sluis B , Taskinen MR , Tokg?zo?lu L , Landmesser U , Laufs U , Wiklund O , Stock JK , Chapman MJ , Catapano AL . 2017. Low-density lipoproteins cause atherosclerotic cardiovascular disease.
null	Evidence from genetic, epidemiologic, and studies Oclinical . A consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal, 38(32): 2459–2472.
null	GBD 2017 Risk Factor Collaborators . 2018. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 392(10159): 1923–1994.
null	Han KH , Tangirala RK , Green SR , Quehenberger O . 1998. Chemokine receptor CCR2 expression and monocyte chemoattractant protein-1-mediated chemotaxis in human monocytes. A regulatory role for plasma LDL. Arteriosclerosie, Thrombosis, and Vascular Biology, 18(12): 1983–1991.
null	Hansson GK , Libby P . 2006. The immune response in atherosclerosis: a double-edged sword. Nature Reviews Immunology, 6(7): 508–519.
null	Hwang HJ , Jung TW , Kim BH , Hong HC , Seo JA , Kim SG , Kim NH , Choi KM , Choi DS , Baik SH , Yoo HJ . 2015. A dipeptidyl peptidase-IV inhibitor improves hepatic steatosis and insulin resistance by AMPK-dependent and JNK-dependent inhibition of LECT2 expression. Biochemical Pharmacoloyg, 98(1): 157–166.
null	Johnson JL . 2007. Matrix metalloproteinases: influence on smooth muscle cells and atherosclerotic plaque stability. Expert Review Cardiovascular Therapy, 5(2): 265–282.
null	Jung TW , Chung YH , Kim HC , Abd El-Aty AM , Jeong JH . 2018. LECT2 promotes inflammation and insulin resistance in adipocytes via P38 pathways. Journal of Molecular Endocrinology, 61(1): 37–45.
null	L'Hermitte A , Pham S , Cadoux M , Couchy G , Caruso S , Anson M , Crain-Denoyelle AM , Celton-Morizur S , Yamagoe S , Zucman-Rossi J , Desdouets C , Couty JP . 2019. Lect2 controls inflammatory monocytes to constrain the growth and progression of hepatocellular carcinoma. Hepatology, 69(1): 160–178.
null	Lim S , Park S . 2014. Role of vascular smooth muscle cell in the inflammation of atherosclerosis. BMB Reports, 47(1): 1–7.
null	Lu XJ , Chen J , Yu CH , Shi YH , He YQ , Zhang RC , Huang ZA , Lv JN , Zhang S , Xu L . 2013. LECT2 protects mice against bacterial sepsis by activating macrophages via the CD209a receptor. Journal of Experimental Medicine, 210(1): 5–13.
null	Lu XJ , Chen Q , Rong YJ , Yang GJ , Li CH , Xu NY , Yu CH , Wang HY , Zhang S , Shi YH , Chen J . 2016. LECT2 drives haematopoietic stem cell expansion and mobilization via regulating the macrophages and osteolineage cells. Nature Communications, 7: 12719.
null	Moore KJ , Tabas I . 2011. Macrophages in the pathogenesis of atherosclerosis. Cell, 145(3): 341–355.
null	Mozaffarian D , Benjamin EJ , Go AS , Arnett DK , Blaha MJ , Cushman M , Das SR , de Ferranti S , Despres JP , Fullerton HJ , Howard VJ , Huffman MD , Isasi CR , Jimenez MC , Judd SE , Kissela BM , Lichtman JH , Lisabeth LD , Liu S , Mackey RH , Magid DJ , McGuire DK , Mohler ER , 3rd, Moy CS , Muntner P , Mussolino ME , Nasir K , Neumar RW , Nichol G , Palaniappan L , Pandey DK , Reeves MJ , Rodriguez CJ , Rosamond W , Sorlie PD , Stein J , Towfighi A , Turan TN , Virani SS , Woo D , Yeh RW , Turner MB . 2016. Heart disease and stroke statistics-2016 update: A report from the American Heart Association. Circulation, 133(4): e38–360.
null	Müller A , Kr?mer SD , Meletta R , Beck K , Selivanova SV , Rancic Z , Kaufmann PA , Vos B , Meding J , Stellfeld T , Heinrich TK , Bauser M , Hütter J , Dinkelborg LM , Schibli R , Ametamey SM . 2014. Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability. Nuclear Medicine and Biology, 41(7): 562–569.
null	Okumura A , Saito T , Otani I , Kojima K , Yamada Y , Ishida-Okawara A , Nakazato K , Asano M , Kanayama K , Iwakura Y , Suzuki K , Yamagoe S . 2008. Suppressive role of leukocyte cell-derived chemotaxin 2 in mouse anti-type II collagen antibody-induced arthritis. Arthritis & Rheumatism, 58(2): 413–421.
null	Ovejero C , Cavard C , Périanin A , Hakvoort T , Vermeulen J , Godard C , Fabre M , Chafey P , Suzuki K , Romagnolo B , Yamagoe S , Perret C . 2004. Identification of the leukocyte cell-derived chemotaxin 2 as a direct target gene of β-catenin in the liver. Hepatology, 40(1): 167–176.
null	Sargeant JA , Aithal GP , Takamura T , Misu H , Takayama H , Douglas JA , Turner MC , Stensel DJ , Nimmo MA , Webb DR , Yates T , King JA . 2018. The influence of adiposity and acute exercise on circulating hepatokines in normal-weight and overweight/obese men. Applied Physiology, Nutrition, and Metabolism, 43(5): 482–490.
null	Slowik V , Apte U . 2017. Leukocyte Cell-Derived Chemotaxin-2: It's role in pathophysiology and future in clinical medicine. Clinical and Translational Science, 10(4): 249–259.
null	Wang Y , Ding WX , Li T . 2018. Cholesterol and bile acid-mediated regulation of autophagy in fatty liver diseases and atherosclerosis. Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids, 1863(7): 726–733.
null	Wolf D , Ley K . 2019. Immunity and inflammation in atherosclerosis. Circulation Research, 124(2): 315–327.
null	Yamagoe S , Mizuno S , Suzuki K . 1998. Molecular cloning of human and bovine LECT2 having a neutrophil chemotactic activity and its specific expression in the liver. Biochimica et Biophysica Acta, 1396(1): 105–113.
null	Ye J , DeBose-Boyd RA . 2011. Regulation of cholesterol and fatty acid synthesis. Cold Spring Harbor Perspectives in Biology, 3(7): a004754.
null	Yoo HJ , Choi KM . 2015. Hepatokines as a link between obesity and cardiovascular diseases. Diabetes & Metabolism Journal, 39(1): 10–15.
null	Yoo HJ , Hwang SY , Choi JH , Lee HJ , Chung HS , Seo JA , Kim SG , Kim NH , Baik SH , Choi DS , Choi KM . 2017. Association of leukocyte cell-derived chemotaxin 2 (LECT2) with NAFLD, metabolic syndrome, and atherosclerosis. PLoS One, 12(4): e0174717.
null	Zhang Z , Zeng H , Lin J , Hu Y , Yang R , Sun J , Chen R , Chen H . 2018. Circulating LECT2 levels in newly diagnosed type 2 diabetes mellitus and their association with metabolic parameters: An observational study. Medicine, 97(15): e0354.
null	Zhong S , Zhao L , Li Q , Yang P , Varghese Z , Moorhead JF , Chen Y , Ruan XZ . 2015. Inflammatory stress exacerbated mesangial foam cell formation and renal injury via disrupting cellular cholesterol homeostasis. Inflammation, 38(3): 959–971.