New insights into immunomodulation via overexpressing lipoic acid synthase as a therapeutic potential to reduce atherosclerosis

Shaomin Tian, Jun Nakamura, Sylvia Hiller, Stephen Simington, Darcy W. Holley, Roberto Mota, Monte S. Willis, Scott J. Bultman, J. Christopher Luft, Joseph M. DeSimone, Zhenquan Jia, Nobuyo Maeda, Xianwen Yi

Research output: Contribution to journalArticle

Abstract

Atherosclerosis is a systemic chronic inflammatory disease. Many antioxidants including alpha-lipoic acid (LA), a product of lipoic acid synthase (Lias), have proven to be effective for treatment of this disease. However, the question remains whether LA regulates the immune response as a protective mechanism against atherosclerosis. We initially investigated whether enhanced endogenous antioxidant can retard the development of atherosclerosis via immunomodulation. To explore the impact of enhanced endogenous antioxidant on the retardation of atherosclerosis via immune regulation, our laboratory has recently created a double mutant mouse model, using apolipoprotein E-deficient (Apoe−/−) mice crossbred with mice overexpressing lipoic acid synthase gene (LiasH/H), designated as LiasH/HApoe−/− mice. Their littermates, Lias+/+Apoe−/− mice, served as a control. Distinct redox environments between the two strains of mice have been established and they can be used to facilitate identification of antioxidant targets in the immune response. At 6 months of age, LiasH/HApoe−/− mice had profoundly decreased atherosclerotic lesion size in the aortic sinus compared to their Lias+/+Apoe−/− littermates, accompanied by significantly enhanced numbers of regulatory T cells (Tregs) and anti-oxidized LDL autoantibody in the vascular system, and reduced T cell infiltrates in aortic walls. Our results represent a novel exploration into an environment with increased endogenous antioxidant and its ability to alleviate atherosclerosis, likely through regulation of the immune response. These outcomes shed light on a new therapeutic strategy using antioxidants to lessen atherosclerosis.

Original languageEnglish (US)
Article number106777
JournalVascular Pharmacology
Volume133-134
DOIs
StateAccepted/In press - 2020

Keywords

  • And immune regulation
  • Antioxidant mouse models
  • Atherosclerosis
  • Oxidized LDL autoantibody
  • Regulatory T cells

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'New insights into immunomodulation via overexpressing lipoic acid synthase as a therapeutic potential to reduce atherosclerosis'. Together they form a unique fingerprint.

  • Cite this

    Tian, S., Nakamura, J., Hiller, S., Simington, S., Holley, D. W., Mota, R., Willis, M. S., Bultman, S. J., Luft, J. C., DeSimone, J. M., Jia, Z., Maeda, N., & Yi, X. (Accepted/In press). New insights into immunomodulation via overexpressing lipoic acid synthase as a therapeutic potential to reduce atherosclerosis. Vascular Pharmacology, 133-134, [106777]. https://doi.org/10.1016/j.vph.2020.106777