CXCL5 May Protect Against Coronary Artery Disease

Older adults with unclogged, healthy arteries have much higher levels of a protein called C-X-C motif chemokine 5 (CXCL5), researchers at University of North Carolina at Chapel Hill report. The finding may point to the genetic basis for coronary artery disease (CAD) and offers a target for therapies and drugs to fight the disease.

“CXCL5 looks to be protective against CAD, and the more CXCL5 you have, the healthier your coronary arteries are. Our findings suggest that there may be a genetic basis to CAD and that CXCL5 may be of therapeutic interest to combat the disease,”

said Jonathan Schisler, assistant professor of pharmacology at the University of North Carolina at Chapel Hill and member of UNC’s McAllister Heart Institute.

Schisler and his colleagues analyzed blood samples and heart scans from 143 people over the age of 65 who were referred to the UNC Medical Center in Chapel Hill for cardiovascular screening. The analysis showed that people with clear arteries had markedly higher levels of CXCL5, as well as genetic variants near the CXCL5 gene, compared to people with more plaque.

CXCL5 Effects

Coronary artery disease is the most common cause of heart attacks and the leading cause of death in the United States. Despite increased awareness of its risk factors and a variety of available treatment options, CAD has remained a persistent public health challenge.

Previous studies linked C-X-C motif chemokine 5 to inflammation, leading some researchers to assume the protein was harmful. But recent research in mice suggested the protein could help limit plaque buildup by changing the composition of fat and cholesterol deposits in the arteries.

CXCL5 levels

Patients with no obstructed blood flow in the coronary arteries had higher levels of CXCL5 (blue) compared to patients with moderate levels (green) or lower levels (yellow) of CXCL5, who had increased severity of coronary obstructions (indicated by the arrows).
Credit: Schisler lab, UNC School of Medicine

Schisler’s finding offers the first evidence that CXCL5 could play a protective role in people, at least in the context of coronary artery disease.

In addition to offering clues about how CAD develops, the study opens new possibilities for prevention and treatment. For example, it may be possible to develop a drug that mimics the effects ofC-X-C motif chemokine 5 or that increases the body’s natural CXCL5 production to help prevent CAD in people at high risk.

Scientists could even potentially leverage the protein to develop a new, nonsurgical approach to help clear clogged arteries.

Coronary Artery Disease Biomarker

There is more, Schisler notes:

“Another potential application of our findings is in the use of CXCL5 as a biomarker for CAD. Although our goal was not to discover biomarkers that may have diagnostic or prognostic applications, it’s possible and worth exploring,”

One limitation of the study is that because all participants were referred for a heart scan, researchers did not include healthy patients. Confirming the role of CXCL5 in CAD and exploring drug development opportunities requires further research.

Schisler says that for him, although the research is in its early stages, honing in on CXCL5 provides him and his team hope in a battle worth fighting.

The UNC-Chapel Hill and the National Institutes of Health funded the study.

Ravi, Saranya et al.
Clinical Evidence Supports a Protective Role for CXCL5 in Coronary Artery Disease
The American Journal of Pathology DOI: http://dx.doi.org/10.1016/j.ajpath.2017.08.006

Top Image: Sergio Bertazzo, Department of Materials, Imperial College London. Density-dependent colour scanning electron micrograph of the surface of human heart (coronary artery) tissue displaying calcification in the form of spherical particles.