Clinical and Industry News

Vaccine for Heart Disease? New Discovery Points to Possibility

A number of research studies have demonstrated inflammation’s role in fueling atherosclerosis, but knowledge of which immune cells are key to this process has been limited until now.

Researchers at the La Jolla Institute for Allergy & Immunology have identified the specific type of immune cells (CD4 T cells) that orchestrate the inflammatory attack on the artery wall. Further, the researchers discovered that these immune cells behave as if they have previously seen the antigen that causes them to launch the attack. “The thing that excites me most about this finding is that these immune cells appear to have ‘memory’ of the molecule brought forth by the antigen-presenting cells,” said Klaus Ley, MD, an expert in vascular immunology, who led the study in mouse models. “Immune memory is the underlying basis of successful vaccines. This means that conceptually it becomes possible to consider the development of a vaccine for heart disease.”

Dr. Ley said he believes the antigen involved is actually a normal protein that the body mistakes as being foreign and therefore launches an immune attack resulting in inflammation in the arteries. “Essentially, we’re saying that there appears to be a strong autoimmune component in heart disease,” he said, explaining that autoimmune diseases result from the body’s mistaken attack on normal cells. “Consequently, we could explore creating a “tolerogenic” vaccine, such as those now being explored in diabetes, which could induce tolerance by the body of this self-protein to stop the inflammatory attack.”

The study was published online August 13 in the Journal of Clinical Investigation.

Dr. Ley cautions that creating a vaccine is a complex process that could take years to develop. However it offers exciting potential. “If successful, a tolerogenic vaccine could stop the inflammation component of heart disease,” he said. “This could probably be used in conjunction with the statins that have already taken a significant chunk out of the numbers of people with heart disease. Together, they could deliver a nice one-two punch that could be important in further reducing heart disease.”

Dr. Ley said antigen-presenting cells take up infectious organisms, foreign materials and self-proteins (in the case of autoimmune diseases) and “chop them into little pieces called epitopes” and then display the pieces on the surface of the cell. “The T cell comes along, and if it has the correct receptors, it will recognize the epitope pieces and make cytokines (a type of immune system soldier molecule) that attack the material and cause inflammation.”

In the study, Dr. Ley and his team used live cell imaging techniques to track immune cells in normal and artherosclerotic mouse aortas. He said in mice with atherosclerosis, there are a large number of antigen-experienced T cells that have already seen certain epitope pieces (from self proteins) that they perceive as foreign. “The T cells talk to the antigen-presenting cells and, in response, make cytokines that launch an attack. This is what makes the inflammation in the vessel wall persistent.” Inflammatory cells join fat and cholesterol to form plaque.

“It wasn’t previously known that antigen-experienced T cells existed in the vessel wall,” said Dr. Ley. “This experiment makes me now believe that it may be possible to build a vaccine for heart disease.”

Depression Linked With Increased Risk of Peripheral Artery Disease

Depression was linked with an increased risk of peripheral artery disease (PAD) in a study of more than 1,000 men and women with heart disease conducted by researchers at the San Francisco VA Medical Center and the University of California.

The study was published electronically on July 26 in the Journal of the American Heart Association.

Marlene Grenon, MD, CM, a vascular surgeon at SFVAMC and an assistant professor of Surgery at UCSF, led the analysis of data from 1,024 participants in the Heart and Soul Study, a prospective study of men and women with coronary artery disease who were followed for an average of approximately seven years.

“We discovered that there was an association between depression and PAD at baseline, and also found that the patients who were depressed at the beginning of the study had a higher likelihood of developing PAD during follow-up at seven years,” said Grenon.

“These findings add to the growing body of research showing the importance of depression in both the development and progression of PAD,” said senior author Beth Cohen, MD, MAS, a physician at SFVAMC and an assistant professor of medicine at UCSF. “This also emphasizes the need for medical providers to be attentive to the mental health of their patients who have developed, or who are at risk for, PAD.”

The authors found that some of the risk for PAD was partly explained by modifiable risk factors such as smoking and reduced physical activity.

“We still don’t know which comes first,” said Grenon. “Is it that patients with PAD become depressed because their mobility is impaired, or that people who are depressed engage in unhealthy behaviors such as smoking and lack of exercise, and are thus more at risk of developing PAD? Or might it be a vicious cycle, where one leads to the other?”

Further research is needed to tease out cause and effect, she said.

The study authors suggest that whatever the initial cause, lifestyle modifications such as being more physically active, eating better, quitting smoking and managing stress more effectively might reduce the risk for the association, as well as potentially address symptoms of both PAD and depression.

“As providers, we can help patients recognize the connections between mental and physical health,” added Cohen. “This may help reduce the stigma of mental health diagnosis and encourage patients to seek treatment for problems such as depression.”

BPA Link to Severe Coronary Artery Stenosis

A research team from the Peninsula College of Medicine and Dentistry (PCMD), University of Exeter, and University of Cambridge has for the first time established a link between high levels of urinary Bisphenol-A (BPA) and severe coronary artery stenosis. The study was published in PLoS ONE on August 15, 2012.

The team analyzed data from 591 patients who participated in the Metabonomics and Genomics Coronary Artery Disease (MaGiCAD) study in Cambridgeshire, United Kingdom. They compared urinary BPA with grades of severity of coronary artery disease (CAD).

The patients were classified into severe, intermediate or normal CAD categories based on narrowing of their coronary arteries using angiography. In all, 385 patients were identified to have severe CAD, 86 intermediate CAD and 120 had normal coronary arteries.

The study shows that urinary BPA concentration was significantly higher in those with severe CAD compared to those with normal coronary arteries.

The results are important because they suggest that associations between urinary BPA and CAD may be specific to narrowing of the arteries.

This is the fourth study led by PCMD, University of Exeter to identify a statistical link between increased levels of urinary BPA and cardiovascular disease.

Other studies related to BPA carried out by the same research team have found associations with altered testosterone and changes in the expression of BPA target genes in men, suggesting that BPA may be more active in the body than previously thought.

The research team was led by Professor David Melzer, Professor of Epidemiology and Public Health at PCMD, University of Exeter. He said: “Our latest study strengthens a growing body of work that suggests that BPA may be adding to known risk factors for heart disease. Full proof will be very difficult to get, as experiments on this in humans are not feasible.”

Professor Tamara Galloway, lead toxicologist on the study from University of Exeter, said: “These results are important because they give us a better understanding of the mechanisms underlying the association between BPA and heart disease.”

Dr. David Mosedale, Chairman of the MaGiCAD Management Committee, added: “This demonstrates the utility of intensively characterised cohorts like MaGiCAD, and highlights the need for further research into the long-term effects of common environmental chemicals such as BPA.”

BPA is used in polycarbonate plastic products such as refillable drinks containers, compact disks, some plastic eating utensils and many other products in everyday use. It is one of the world’s highest production volume chemicals, with 5.16 million tons produced in 2008 (source: Chemical Weekly 2009).