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A Novel Role of Id1 in Regulating Oscillatory Shear Stress-Mediated Lipid Uptake in Endothelial Cells

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Abstract

Inhibitor of DNA binding 1 (Id1) has been shown to be involved in adipogenesis and metabolism, which may contribute to atherosclerotic progression. However, it remains unclear how Id1 regulates endothelial cell functions and atherosclerosis in response to oscillatory shear stress. The current study aims to evaluate the effects of oscillatory shear stress on LDL uptake by endothelial cells and to delineate the roles of Id1 in this process. Using an in vivo ligation model of ApoE−/− mice and applying low and oscillatory shear stress (OSS) in vitro, we found that OSS can effectively promote lipid uptake. In vivo en face staining results showed that OSS down-regulated Id1 expression. In vitro, OSS activated Id1 transiently but eventually inhibited its expression with time. Overexpression of Id1 can abolish OSS-mediated lipid uptake in ECs. In addition, Id1 overexpression and knockdown experiments demonstrated that Id1 can regulate LDLR expression to influence lipid uptake. Immunoprecipitation and subcellular localization results further suggested that Id1 can combine with sterol regulatory element-binding protein1 (SREBP1), which may be related to the Id1-mediated LDLR down-expression. Our study shows a biomechanical role of Id1 in endothelial cells’ uptake of lipid by down-regulating LDLR, which could help understand how oscillatory flow affects atherosclerotic development.

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References

  1. Asakura, T., and T. Karino. Flow patterns and spatial distribution of atherosclerotic lesions in human coronary arteries. Circ. Res. 66:1045–1066, 1990.

    Article  CAS  PubMed  Google Scholar 

  2. Brooks, A. R., P. I. Lelkes, and G. M. Rubanyi. Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol. Genom. 9:27–41, 2002.

    Article  CAS  Google Scholar 

  3. Chatzizisis, Y. S., A. U. Coskun, M. Jonas, E. R. Edelman, C. L. Feldman, and P. H. Stone. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J. Am. Coll. Cardiol. 49:2379–2393, 2007.

    Article  CAS  PubMed  Google Scholar 

  4. Chiu, J. J., and S. Chien. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol. Rev. 91:327–387, 2011.

    Article  PubMed  Google Scholar 

  5. Corti, R., V. Fuster, J. J. Badimon, R. Hutter, and Z. A. Fayad. New understanding of atherosclerosis (clinically and experimentally) with evolving MRI technology in vivo. Ann N Y Acad Sci 947:181–195, 2001; (discussion 195-188).

    Article  CAS  PubMed  Google Scholar 

  6. Cuhlmann, S., K. Van der Heiden, D. Saliba, J. L. Tremoleda, M. Khalil, M. Zakkar, H. Chaudhury, A. Luong le, J. C. Mason, I. Udalova, W. Gsell, H. Jones, D. O. Haskard, R. Krams, and P. C. Evans. Disturbed blood flow induces RelA expression via c-Jun N-terminal kinase 1: a novel mode of NF-kappaB regulation that promotes arterial inflammation. Circ. Res. 108:950–959, 2011.

    Article  CAS  PubMed  Google Scholar 

  7. Eberle, D., B. Hegarty, P. Bossard, P. Ferre, and F. Foufelle. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 86:839–848, 2004.

    Article  CAS  PubMed  Google Scholar 

  8. Farmer, S. R. Transcriptional control of adipocyte formation. Cell Metab. 4:263–273, 2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Getz, G. S., and C. A. Reardon. Do the Apoe−/− and Ldlr−/− mice yield the same insight on atherogenesis? Arterioscler. Thromb. Vasc. Biol. 36:1734–1741, 2016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Goldstein, J. L., and M. S. Brown. The LDL receptor. Arterioscler. Thromb. Vasc. Biol. 29:431–438, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Goldstein, J. L., T. Kita, and M. S. Brown. Defective lipoprotein receptors and atherosclerosis. Lessons from an animal counterpart of familial hypercholesterolemia. N. Engl. J. Med. 309:288–296, 1983.

    Article  CAS  PubMed  Google Scholar 

  12. Guo, D., S. Chien, and J. Y. Shyy. Regulation of endothelial cell cycle by laminar versus oscillatory flow: distinct modes of interactions of AMP-activated protein kinase and Akt pathways. Circ. Res. 100:564–571, 2007.

    Article  CAS  PubMed  Google Scholar 

  13. Hansson, G. K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 352:1685–1695, 2005.

    Article  CAS  PubMed  Google Scholar 

  14. Huo, Y., T. Wischgoll, and G. S. Kassab. Flow patterns in three-dimensional porcine epicardial coronary arterial tree. Am. J. Physiol. Heart Circ. Physiol. 293:H2959–H2970, 2007.

    Article  CAS  PubMed  Google Scholar 

  15. Lasorella, A., R. Benezra, and A. Iavarone. The ID proteins: master regulators of cancer stem cells and tumour aggressiveness. Nat. Rev. Cancer 14:77–91, 2014.

    Article  CAS  PubMed  Google Scholar 

  16. Libby, P., and P. Theroux. Pathophysiology of coronary artery disease. Circulation 111:3481–3488, 2005.

    Article  PubMed  Google Scholar 

  17. Lin, K., P. P. Hsu, B. P. Chen, S. Yuan, S. Usami, J. Y. Shyy, Y. S. Li, and S. Chien. Molecular mechanism of endothelial growth arrest by laminar shear stress. Proc Natl Acad Sci USA 97:9385–9389, 2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu, Y., B. P. Chen, M. Lu, Y. Zhu, M. B. Stemerman, S. Chien, and J. Y. Shyy. Shear stress activation of SREBP1 in endothelial cells is mediated by integrins. Arterioscler. Thromb. Vasc. Biol. 22:76–81, 2002.

    Article  PubMed  Google Scholar 

  19. Liu, D., Z. Ding, M. Wu, W. Xu, M. Qian, Q. Du, L. Zhang, Y. Cui, J. Zheng, H. Chang, C. Huang, D. Lin, and Y. Wang. The apolipoprotein A-I mimetic peptide, D-4F, alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway. J Mol Cell Cardiol 105:77–88, 2017.

    Article  CAS  PubMed  Google Scholar 

  20. Lusis, A. J. Atherosclerosis. Nature 407:233–241, 2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nam, D., C. W. Ni, A. Rezvan, J. Suo, K. Budzyn, A. Llanos, D. Harrison, D. Giddens, and H. Jo. Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis. Am. J. Physiol. Heart Circ. Physiol. 297:H1535–H1543, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ni, C. W., H. Qiu, A. Rezvan, K. Kwon, D. Nam, D. J. Son, J. E. Visvader, and H. Jo. Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow. Blood 116:e66–e73, 2010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Niwa, K., T. Kado, J. Sakai, and T. Karino. The effects of a shear flow on the uptake of LDL and acetylated LDL by an EC monoculture and an EC-SMC coculture. Ann. Biomed. Eng. 32:537–543, 2004.

    Article  PubMed  Google Scholar 

  24. Patil, M., B. K. Sharma, and A. Satyanarayana. Id transcriptional regulators in adipogenesis and adipose tissue metabolism. Front. Biosci. (Landmark Ed) 19:1386–1397, 2014.

    Article  Google Scholar 

  25. Qiu, J., Q. Peng, Y. Zheng, J. Hu, X. Luo, Y. Teng, T. Jiang, T. Yin, C. Tang, and G. Wang. OxLDL stimulates Id1 nucleocytoplasmic shuttling in endothelial cell angiogenesis via PI3 K pathway. Biochim. Biophys. Acta 1361–1369:2012, 1821.

    Google Scholar 

  26. Qiu, J., G. Wang, Y. Zheng, J. Hu, Q. Peng, and T. Yin. Coordination of Id1 and p53 activation by oxidized LDL regulates endothelial cell proliferation and migration. Ann. Biomed. Eng. 39:2869–2878, 2011.

    Article  PubMed  Google Scholar 

  27. Satyanarayana, A., K. D. Klarmann, O. Gavrilova, and J. R. Keller. Ablation of the transcriptional regulator Id1 enhances energy expenditure, increases insulin sensitivity, and protects against age and diet induced insulin resistance, and hepatosteatosis. FASEB J. 26:309–323, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Seale, P., S. Kajimura, and B. M. Spiegelman. Transcriptional control of brown adipocyte development and physiological function—of mice and men. Genes Dev. 23:788–797, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sprague, E. A., B. L. Steinbach, R. M. Nerem, and C. J. Schwartz. Influence of a laminar steady-state fluid-imposed wall shear stress on the binding, internalization, and degradation of low-density lipoproteins by cultured arterial endothelium. Circulation 76:648–656, 1987.

    Article  CAS  PubMed  Google Scholar 

  30. VanderLaan, P. A., C. A. Reardon, and G. S. Getz. Site specificity of atherosclerosis: site-selective responses to atherosclerotic modulators. Arterioscler. Thromb. Vasc. Biol. 24:12–22, 2004.

    Article  CAS  PubMed  Google Scholar 

  31. Yokoyama, C., X. Wang, M. R. Briggs, A. Admon, J. Wu, X. Hua, J. L. Goldstein, and M. S. Brown. SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell 75:187–197, 1993.

    Article  CAS  PubMed  Google Scholar 

  32. Zhang, J., and M. H. Friedman. Adaptive response of vascular endothelial cells to an acute increase in shear stress magnitude. Am. J. Physiol. Heart Circ. Physiol. 302:H983, 2012.

    Article  CAS  PubMed  Google Scholar 

  33. Zhou, J., P. L. Lee, C. S. Tsai, C. I. Lee, T. L. Yang, H. S. Chuang, W. W. Lin, T. E. Lin, S. H. Lim, S. Y. Wei, Y. L. Chen, S. Chien, and J. J. Chiu. Force-specific activation of Smad1/5 regulates vascular endothelial cell cycle progression in response to disturbed flow. Proc. Natl. Acad. Sci USA 109:7770–7775, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank Mr Yiming Zheng and Mr Dongyu Jia at Florida State University for assistance with editing the manuscript. This study was supported by grants from the National Natural Science Foundation of China (31370949, 11332003, 11572064), the National Key Technology R&D Program of China (2016YFC1102305, 2016YFC1101101) and the Fundamental Research Funds for the Central Universities (106112017CDJZRPY0202, 106112017CDJPT230001, 106112017CDJQJ238814) as well as the Public Experiment Center of State Bioindustrial Base (Chongqing), China.

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Authors and Affiliations

  1. Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China

    Kang Zhang, Yidan Chen, Tian Zhang, Lu Huang, Yi Wang, Tieying Yin, Juhui Qiu, Hans Gregersen & Guixue Wang

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  1. Kang Zhang
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  2. Yidan Chen
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  3. Tian Zhang
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Correspondence to Guixue Wang.

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Associate Editor Debra T. Auguste oversaw the review of this article.

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Zhang, K., Chen, Y., Zhang, T. et al. A Novel Role of Id1 in Regulating Oscillatory Shear Stress-Mediated Lipid Uptake in Endothelial Cells. Ann Biomed Eng 46, 849–863 (2018). https://doi.org/10.1007/s10439-018-2000-3

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