Despite the advances made in the cardiovascular field, scientists are still looking for therapies that can lower the occurrence of cardiovascular events. In a previous post, I discussed the debate around the benefit of high levels of HDL – or “good cholesterol” – and how when it comes to HDL, quality over quantity matters most. A major way to measure HDL quality is by examining its capacity to remove lipids from lipid-laden cells also known as cholesterol efflux capacity – or CEC. In large clinical studies, CEC correlates better with predicting cardiovascular incidents than does HDL quantity. In this month’s post, I would like to shed light on a particular component of the HDL molecule, Apolipoprotein AI – or ApoAI. The reason is two folds. First, ApoAI is the most functional component of the HDL molecule. Second, I have been studying the effect of ApoAI on the immune system and atherosclerosis for a few years now, and thus know about the therapeutic potential of this molecule.
ApoAI is a protein made in the liver that pairs up with phospholipids to form a lipid-poor molecule that allows for cholesterol efflux from macrophages. Due to this unique property, scientists and clinicians have been interested in understanding how to use ApoAI as a therapeutic agent to reduce cardiovascular incidents. In the past few months, three studies published in the ATVB journal have looked closely at ApoAI, its role in heart disease and correlation with CEC. The most recent of these studies – and perhaps, the most exciting due to its potential therapeutic application – was published in this month’s issue of the journal in the clinical and population studies section. In this study, atherosclerosis patients and healthy individuals were given an infusion of human ApoAI (or CSL112) and the researchers examined the patients’ serum capacity to efflux cholesterol. Because atherosclerosis patients show lower capacity to efflux cholesterol, the authors wanted to see how these patients faired after receiving ApoAI infusions. As one would hope, patients that received CSL112 showed an increase in CEC despite their health condition, showing promise of CSL112 as a therapeutic approach to reduce atherosclerosis and lower the risk of heart disease.
It is also important to note that ApoAI has non-cardiovascular properties, mainly anti-inflammatory ones. ApoAI can reduce the incident of rheumatoid arthritis, lupus and Alzheimer’s disease. ApoAI also is capable of affecting cells of the immune system suggesting that ApoAI effects can reach beyond heart disease to other inflammatory and immune conditions. As more clinical studies continue to investigate how ApoAI infusions work in patients, it will be interesting to see its impact not just on the cardiovascular system and its health but the immune system as well. Do patients that receive ApoAI develop less autoimmune disease or is the effect of ApoAI limited to cholesterol efflux?
One of the main concerns that remain to be addressed with ApoAI is its administration. So far, patients receiving ApoAI get it through an infusion every week. In the study mentioned above some patients were given two infusions per week for four weeks. Patient compliance and feasibility is a caveat in this setting and if ApoAI is to be used more broadly as a preventative therapy against cardiovascular disease, a more patient-friendly approach is needed. Is it possible to make a version of ApoAI that can be easily administered? One would only hope that because of its promise and as we discover more about what makes ApoAI so unique, that such a formula would soon become available.
Dalia Gaddis is a postdoctoral fellow at the La Jolla Institute for Allergy and Immunology. She has a Ph.D. in microbiology and immunology. She is currently working on understanding the interactions between the immune system and atherosclerosis development.