Innovations in Atherosclerosis Have Potential to Benefit Patients With CKD, HIV

Developments in atherosclerosis were among the many novel points of progress highlighted at this year’s American Heart Association (AHA) conference. As the latest research sheds light on the new pathways, therapeutic possibilities, and mechanisms associated with vascular disease, Masanori Aikawa, MD, PhD, professor of medicine, Harvard Medical School, explored how innovations in atherosclerosis could benefit larger patient populations and be applicable to other diseases.

This transcript has been lightly edited for clarity.

Transcript

Can you walk us through some of the novel discoveries in the field of atherosclerosis, and how these might shape future therapies?

So first of all, the approach of my group might be a little bit different from others. We use a so-called “systems approach” that involves omics, screening and network science, and some computational programs like bioinformatics and machine learning to holistically explore disease mechanisms, rather than testing each specific hypothesis. And then we've been particularly focusing on the impact of chronic kidney disease (CKD) on a cardiovascular event, particularly with the focus on macrophage biology.

More recently, we've been working on the clinical impact of HIV infection. Although, because of the innovative therapeutics, people don't die of AIDS; however, HIV infection continues inside our organs, and then those people have kind of chronic, low-degree inflammation. The good news is, they survive for a long, long time. But on the other hand, that particular group is aging. Therefore, we predict that there will be lots of cardiovascular events—particularly in HIV survivors on antiretroviral therapeutics.

Then, we've been working on these aspects using a systems approach. This sort of approach enables you to see something you could miss otherwise, and we found several new mechanisms by which either chronic kidney disease or chronic HIV infection activate pro-inflammatory responses in macrophages in ways that would potentially increase the cardiovascular risk in those patients. There are several mechanisms we are working on. Some of those pathways, using this sort of approach, you can see things you wouldn't have seen using a traditional approach. For example, machine learning can make the impossible possible and the invisible visible; a holistic approach can find unexpected mechanisms. That's what we've been really excited about in the past several years.