NEW YORK (GenomeWeb) – A research team from the University of North Carolina at Chapel Hill has found a link between the protein CXCL5 and potential protection against the development of coronary artery disease (CAD) in old age.
CAD is the most common cause of heart attacks and the leading cause of death in the US. While there has been increased public awareness of risk factors and a variety of available treatment options, CAD has remained a public health challenge.
The researchers presented their findings this week at the American Society for Investigative Pathology annual meeting during Experimental Biology 2016 in San Diego.
For this study, the researchers collected blood samples and performed heart scans on 143 people over age 65, who had been referred for cardiovascular screening. They performed gene expression analysis on the blood samples using Agilent two-color microarrays. Each sample was co-hybridized with a human reference RNA sample. The researchers also genotyped the blood samples on the Affymetrix human SNP 6.0 array.
The research team identified 553 genes that correlated with CAD severity. These genes consisted of clusters of inflammatory genes, p38 MAPK signaling genes, and leukocyte activation, consistent with a heightened inflammatory state.
The researchers noted an enriched expression of genes related to leukocyte activation that suggested that inflammation mediated by leukocyte mobilization impacts the CAD gene expression signature. They believe this might impact the extent of the disease as well.
Then, the researchers looked to identify circulating molecules in the blood that may play a role in inflammatory response associated with CAD gene expression. Based on their observations, the researchers decided to look more closely at the protein CXCL5 due to its ability to activate p38 and its proposed role as a mediator in the formation of inflammatory microenvironment in cancer and tuberculosis.
When they analyzed the blood samples for CXCL5, they found that people with clearer arteries had higher levels of the protein than in people with more plaque buildup in their arteries.
This inverse relationship at first seemed counterintuitive; however, it supported research published in the Journal of Clinical Investigation in 2013 that found a protective role for CXCL5 in the context of atherosclerosis in mice.
The researchers did note that one limitation of the study was the lack of a healthy control group. They indicated that future research with such a group would be needed before it would be possible to confirm the role of CXCL5 in CAD.
"Identifying the regulation of CXCL5 may provide insight into the genetic contribution to coronary artery disease," Jonathan Schisler, an assistant professor of pharmacology at McAllister Heart Institute at UNC Chapel Hill and researcher on the study, told GenomeWeb in an email.
Going forward, Schisler and his colleagues want to identify other molecules that may play a role in the development of CAD. "Although CXCL5 is considered a proinflammatory cytokine, identifying partial agonists or the pathways that contribute to its protective qualities may provide new therapies and therapeutic targets for heart disease," he said.