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

Abstract

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Effects of Apolipoprotein A-I/High-Density Lipoprotein Cholesterol on Atherosclerotic Vascular Disease

“…Cumulatively, the findings from Morton et al. (11) support the concept of a functional loss of vasoprotective properties of apoA-I and HDL under advanced age and diseased milieu conditions. Of note, a recent report demonstrated that accumulated apoA-I in human atheromas is largely dysfunctional due to extensive oxidation by myeloperoxidase with subsequently impaired ABCA1-dependent cholesterol acceptor activity (14) .…”

“…The findings from Morton et al. (11) are of particular clinical interest in light of therapeutic strategies to selectively raise apoA1. Such strategies have already been tested, for example, with the agent RVX-208 in the ASSERT trial (Efficacy and Safety of a Novel Oral Inducer of Apolipoprotein A-I Synthesis in Statin-Treated Patients With Stable Coronary Artery Disease), although it failed to achieve a significant change in plaque regression in patients with coronary disease as assessed by intravascular ultrasound imaging (16) .…”

“…Morton et al. (11) , therefore, provide clear evidence that increasing apoA-I may have stage-dependent effects on the progression of atherosclerosis. In early-stage atherosclerosis and in younger ApoE −/− mice apoA-I infusion was effective in preventing atheroma growth with decreased plaque macrophage content and reduced circulating inflammatory markers.…”

“…In this issue of JACC: Basic to Translational Science , Morton et al. (11) report on marked differences between the effects of administration of apolipoprotein A-I (apoA-I), the major structural protein of HDL on atherosclerotic vascular disease between administration in early versus late atherosclerotic vascular disease (12) . This study is highly relevant toward understanding the differences between the earlier experimental studies, suggesting a protective effect of HDL infusion and more recent clinical studies, demonstrating a lack of beneficial effects of apoA-I/HDL infusions in patients with later stages of atherosclerotic vascular disease.…”

Ratio of Baseline Monocyte Counts to Apolipoprotein A1 is Associated with Long-Term Mortality in Patients with Coronary Artery Disease After Percutaneous Coronary Intervention

“…Apolipoprotein a1 (ApoA1) is the main component of HDL, and it may affect the anti-inflammatory and anti-oxidative effects of HDL via various mechanisms [10]. A large number of animal studies confirmed that high ApoAI expression reduced the volume of atherosclerotic plaques [11][12][13][14].…”