Heart artery plaque immune cells cross-react with virus and vascular proteins – a potential cause of heart attack

by Amanda Chase, PhD
May 13, 2022

Researchers at the Stanford Cardiovascular Institute have discovered how viruses like influenza and SARS-CoV-2 as well as their associated vaccines may increase the risk of heart attack, stroke, heart inflammation, and other cardiovascular complications. “Flu has long been associated with heart attack and heart inflammation. The recent COVID-19 pandemic has further highlighted the relationship between viruses and cardiovascular complications. The reasons why respiratory viral infections increase cardiovascular risk remain unclear,” said Patricia Nguyen, MD, a member of the institute and an Assistant Professor in the Division of Cardiovascular Medicine (Department of Medicine) at Stanford University. “If we can better understand the connection between viruses and clotting, we can develop diagnostic tests to identify patients at highest risk and novel therapies to prevent these potentially deadly complications.”

Overview of how the immune cells (T cells and dendritic cells) can react to viruses. Those T cells can become memory T cells, which were found in coronary artery plaque. These T cells may recognize a self-antigen epitope that resembles the viral antigen epitope (mimicry), ultimately implicating T cells in coronary artery disease progression. Figure drawn by Katlyn Alexis Carey from Palo Alto High School.

The Research was recently published in the journal Circulation Research. Nguyen and Professor Mark Davis, PhD, are senior authors on the paper. Dr. Davis is the Burt and Marion Avery Family Professor in the School of Medicine and Director of the Stanford Institute for Immunity, Transplantation, and Infection. Roshni Roy Chowdhury, PhD, who is a former postdoctoral fellow in Dr. Nguyen’s lab, is the co-first author along with Jessica D’Addabbo, BS, a former research assistant, and Xianxi Huang, MD, PhD a former postdoctoral fellow in Dr. Nguyen’s lab.

Coronary artery disease is a leading cause of morbidity and mortality worldwide. Recent studies have found that plaque buildup in the heart arteries is composed of immune cells. An important immune cell subset found in plaques is the T cell population, master regulators of all immune cells. T cells can recruit additional immune cells to sites of inflammation and possess memory and defend the body against repeat attacks by foreign invaders. Using innovative technologies that allowed the investigators to analyze plaque cells at a single cell level, they found that memory T cells make up a large proportion of the cell components of the plaque. Surprisingly, the investigators found that memory T cells in coronary artery plaque were specific for influenza and SARS-CoV-2. But why were the virus-specific memory T cells found, and why were they in patients who were not actively infected? “Viruses do not have a natural affinity to plaques, so their presence in plaque is intriguing,” says Nguyen.

The investigators were able to show that the T cells can be activated and expand, may mediate an attack on self that triggers atherosclerosis development and progression, and can exert pro- and anti-inflammatory effects. “These findings suggest that a subset of patients may be vulnerable to auto-immune clotting complications induced by previous viral infections. Development of diagnostic assays to identify these vulnerable patients is critical so that we may develop appropriate prevention and immune-based treatment strategies for these patients,” concluded Dr. Nguyen.

Patricia Nguyen, MD

Mark Davis, PhD