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High-Density Lipoprotein in Lupus: Disease Biomarkers and Potential Therapeutic Strategy

Sang Yeop Kim1, Minzhi Yu1, Emily E Morin1

  • 1University of Michigan, Ann Arbor.

Arthritis & Rheumatology (Hoboken, N.J.)
|July 28, 2019
PubMed

Insights

Systemic lupus erythematosus (SLE) patients develop dysfunctional high-density lipoproteins (HDLs) that accelerate atherosclerosis. These altered HDLs promote inflammation and cardiovascular disease (CVD), suggesting HDL-targeted therapies for lupus patients.

Area of Science:

  • Cardiovascular Science
  • Immunology
  • Lipid Metabolism

Background:

  • Systemic lupus erythematosus (SLE) is linked to accelerated atherosclerosis and cardiovascular disease (CVD).
  • Traditional risk factors do not fully explain the increased CVD risk in SLE patients.
  • Altered high-density lipoproteins (HDLs) are implicated in the heightened atherosclerosis observed in SLE.

Purpose of the Study:

  • To investigate the role of high-density lipoproteins (HDLs) in the accelerated atherosclerosis of Systemic lupus erythematosus (SLE).
  • To characterize the functional and compositional changes in HDLs from SLE patients.
  • To explore the potential of HDL-based therapies for cardiovascular complications in SLE.

Main Methods:

  • Analysis of HDL composition, including proteomic and lipidomic signatures.
  • Assessment of HDL function, such as cholesterol efflux capacity, antioxidant, and anti-inflammatory properties.
  • Evaluation of HDL's role in promoting or inhibiting inflammation and atherogenesis in the context of SLE.

Main Results:

  • SLE patients exhibit reduced levels of high-density lipoproteins (HDLs) with altered composition and function.
  • Systemic inflammation, oxidative stress, and autoimmunity in SLE lead to dysfunctional, proinflammatory HDLs.
  • These dysfunctional HDLs demonstrate impaired atheroprotective functions, including reduced cholesterol efflux and diminished anti-inflammatory and antioxidant capacities.
  • Dysfunctional HDLs may actively promote atherogenesis by inducing vascular inflammation.

Conclusions:

  • Dysfunctional high-density lipoproteins (HDLs) are a significant factor in accelerated atherosclerosis and cardiovascular disease (CVD) in Systemic lupus erythematosus (SLE) patients.
  • Altered HDLs in SLE possess proinflammatory properties and impaired atheroprotective functions.
  • Dysfunctional HDLs represent a potential biomarker for atherosclerosis in SLE and suggest HDL-targeted therapies, such as reconstituted HDLs, as a promising treatment strategy for CVD in this population.

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