Strikingly Different Atheroprotective Effects of Apolipoprotein A-I in Early- Versus Late-Stage Atherosclerosis

• Published in: JACC. Basic to translational science 2018-04, Vol.3 (2), p.187-199
• Main Authors: Morton, Jamie, MBBS, PhD, Bao, Shisan, MD, PhD, Vanags, Laura Z., BSc, PhD, Tsatralis, Tania, BSc, Ridiandries, Anisyah, BSc, PhD, Siu, Chung-Wah, MBBS, MD, Ng, Kwong-Man, BSc, PhD, Tan, Joanne T.M., BSc, PhD, Celermajer, David S., MBBS, PhD, Ng, Martin K.C., MBBS, PhD, Bursill, Christina A., BSc, PhD
• Format: Article
• Language: English
• Subjects: atherosclerosis; Cardiovascular; cholesterol; high-density lipoproteins; PRECLINICAL RESEARCH
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2017.11.004

[Display omitted] •The atheroprotective effects of apoA-I are dependent on the plaque stage from which apoA-I is infused.•The atheroprotective effects of apoA-I infusions are also impaired in older mice with a greater disease milieu.•Ex vivo studies with mouse HDL found an impairment in HDL functionality with increasing disease/age of the mice as well as a reduced ability of apoA-I infusions to improve the atheroprotective functions of HDL.•Our study provides understanding regarding the disparity between the very positive results of HDL/apoA-I raising in preclinical studies, largely performed in younger animals with early-stage disease, and the large-scale HDL-raising clinical trials in more elderly patients with established plaque that have failed to show benefit. Preclinical studies have shown benefit of apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL) raising in atherosclerosis; however, this has not yet translated into a successful clinical therapy. Our studies demonstrate that apoA-I raising is more effective at reducing early-stage atherosclerosis than late-stage disease, indicating that the timing of HDL raising is a critical factor in its atheroprotective effects. To date, HDL-raising clinical trials have only been performed in aged patients with advanced atherosclerotic disease. Our findings therefore provide insight, related to important temporal aspects of HDL raising, as to why the clinical trials have thus far been largely neutral.