Heart Disease Inflammation and Cancer Medication

According to a new study, an investigational cancer medication may reduce the advancement of atherosclerosis, which leads to heart disease.

The study, led by experts at NYU Grossman School of Medicine, investigated the factors underlying atherosclerosis, a condition in which fatty deposits accumulate in blood vessels. As this buildup hardens into plaques and triggers erroneous immunological responses (inflammation), it can obstruct blood flow, resulting in a heart disease

The latest study, published on June 8 in the journal Nature Cardiovascular Research, found that plasma (the liquid part of blood) from patients with atherosclerotic disease causes an abnormally strong inflammatory signal in blood immune cells. Further research revealed that the drug saracatinib reduced inflammatory signaling in human blood and sick tissue samples by more than 90%.

“Our findings provide new insight into the inflammatory mechanisms in atherosclerosis and suggest for the first time that saracatinib may offer an effective therapy in cases where standard therapy, in the form of statins, fails to help,” says study co-lead author Letizia Amadori, Ph.D., a senior research scientist at NYU Langone Health.

Statins are prescribed by doctors to lower dangerous lipids in the blood, however studies reveal that even when plaque deposits are decreased, inflammation lingers in many patients, leaving them at high risk for a heart disease. The causes of this chronic immune response in patients, according to the study authors, are not entirely known, and anti-inflammatory medications are occasionally ineffective in patient studies.

The researchers compared blood samples from 34 men and women with atherosclerotic cardiovascular disease (ASCVD), all of whom were taking statins, to samples from 24 healthy donors for the study.

To pinpoint saracatinib, the researchers looked into 4,823 genes, 277 of which are already known to play a role in inflammation and produce cytokines and other substances that cause a persistent immune response.

According to Amadori, the scientists reasoned that if a certain medicine could prevent all of these molecules from being produced, it would be able to calm the response.

Rather than developing a new medicine from start, the researchers looked to a list of pharmaceuticals that were previously approved or being studied for different applications. They specifically searched the Library of Integrated Network-Based Cellular Signatures dataset from the National Institutes of Health, which contains hundreds of thousands of test results mapping the effects of various molecules, signaling proteins, and genetic changes on human cells.

Because saracatinib was shown in this study to reverse target gene expression, the process by which genes are turned on to make proteins, the authors tested it in human cells, diseased tissue, and animal models to see if it could actually stop, slow, or reverse inflammation caused by ASCVD.

Among the findings were that saracatinib inhibits gene activity that produces inflammatory proteins such as interleukin-1 beta and interleukin-6, which sustain ASCVD’s immunological responsiveness. In a previous trial, an inhibitor of interleukin-1 beta was demonstrated to successfully prevent heart disease. At the same time, the medicine increased the expression of genes that produce proteins that assist clear up plaque plaques by moving fat away from the arteries.

In additional rabbit studies, saracatinib reduced plaque-based inflammation by around 97% when compared to untreated animals. In rats, the same therapy resulted in an 80% drop in cells associated with inflammation in plaques and a reduction in plaque deposits ranging from 48% to 70%, according to Amadori.

“Our reverse-engineering method of finding new uses for old drugs can in theory be harnessed to uncover therapies for practically any disease that involves inflammation,” said study senior author Chiara Giannarelli, MD, Ph.D. “Since these chemicals have already been tested for safety, this technique offers a swift and cost-effective approach to pharmaceutical development.”

Giannarelli, an associate professor in the Departments of Medicine and Pathology at NYU Langone, says the research team will utilize the same approach to look at potential treatments for additional inflammatory disorders connected to ASCVD, such as rheumatoid arthritis or type 2 diabetes.

However, Giannarelli warns that, while saracatinib appears promising, it must still be clinically studied to guarantee that it works in people.

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