The Clearly Misunderstood Case of ApoB-100

See allHide authors and affiliations

Science Translational Medicine  28 Nov 2012:
Vol. 4, Issue 162, pp. 162ec214
DOI: 10.1126/scitranslmed.3005332

As often happens in nature, “bad” may not always be wrong, and a balance of forces exists within complex biological systems such as the human body. Due to its major impact on human life, cardiovascular disease is a key area in biomedical research. The understanding that narrowing of blood vessels is not just due to the deposition of fat, but to a process driven by inflammation, was a pivotal discovery from the past 3 decades of medical history.

Low-density lipoproteins (LDL) transport the highest quantities of cholesterol in the blood and therefore are usually known as “bad fats.” In addition to cholesterol, LDL contains a protein called apolipoprotein B-100 (apoB-100), which makes these fat carriers soluble. However, apoB-100 is also required for normal removal and metabolism of LDL by the liver. The current paradigm in cardiovascular research establishes that the accumulation of oxidized LDL particles within the arterial walls is a key mechanism contributing to disease. Through the recognition of apoB-100 by macrophages, LDL accumulates in plaques within the arterial walls, inducing a prolonged activation of inflammatory responses and resulting in enlargement and weakening of the plaques. This weakening is responsible for the plaques’ eventual rupture, leading to the sudden blockage of blood flow that causes a myocardial infarction or a stroke.

Sigel and colleagues have now presented a different role for apoB-100. The investigators showed that the interaction of apoB-100 with lipoteichoic acid (LTA) from Staphylococcus aureus has anti-inflammatory effects that could interfere with the body’s response to infection. Through a combination of in vitro and in vivo experiments, the authors showed that this anti-inflammatory effect selectively mapped to apoB-100–containing LDL particles and not to other lipid-carrying particles in the blood. The interaction of apoB-100 and LTA dampened the white blood cells’ release of proinflammatory molecules known as cytokines, which are crucial in the defense against bacterial invasion. Recent reports have noted anti-inflammatory and anti-atherosclerotic effects of peptides derived from apoB-100. However, this is the first study reporting the lipoprotein’s effect on bacterial infection.

This discovery highlights the question of whether hypercholesterolemia could be a risk factor that makes us more susceptible to infections or whether this change in the immune response could actually be protective against harmful inflammation. Based on these results, could we start hypothesizing that the fight against obesity is also a battle for preventing microbial infections? Or is the interaction between bacterial pathogens and apo-B100 an illustration of the body’s ability to protect itself from excess inflammation and damage? The answers will certainly be complex, but the new intriguing findings should stimulate additional research that could transform our understanding of disease progression.

S. Sigel et al., Apolipoprotein B100 is a suppressor of Staphylococcus aureus-induced innate immune responses in humans and mice. Eur. J. Immunol. 42, 2983–2989 (2012). [Abstract]

Stay Connected to Science Translational Medicine

Navigate This Article