Peripheral artery disease (PAD) is a narrowing of the peripheral arteries that carry blood away from the heart to other parts of the body. Both PAD and coronary artery disease are caused by atherosclerosis, the buildup of fatty plaque in the arteries. New research by researchers at Washington University School of Medicine in St. Louis demonstrates that high levels of a specific protein circulating in the blood accurately detect a severe type of peripheral artery disease.
The protein, called circulating fatty acid synthase (cFAS), is an enzyme that manufactures saturated fatty acids. The new study suggests that cFAS may play a potential role in the plaque formation of cardiovascular disease.
Their findings appear in the journal Scientific Reports in a paper titled, “Prevalence of elevated serum fatty acid synthase in chronic limb-threatening ischemia.”
“There are currently no serum-based evaluations that can corroborate the severity of PAD,” the researchers wrote. “In this cross-sectional study, we assessed the prevalence of elevated serum fatty acid synthase (cFAS) in patients with chronic limb-threatening ischemia (CLTI) and evaluated the accuracy of its use in detecting this condition.”
About 12 million people in the United States have some form of PAD, and about one million of these patients develop a severe form called CLTI. In severe cases, patients may need to have the diseased leg amputated.
“These patients are at risk of losing their legs, which is devastating to quality of life,” explained senior author Mohamed A. Zayed, MD, PhD, an associate professor of surgery and of radiology. “They lose their capacity to walk, and about half of them die within the next two years. We need to identify these patients sooner, so we can help treat them aggressively much earlier in the disease course. Our data suggest that levels of cFAS in the blood could be an accurate predictor for which patients are at high risk of the severe forms of this condition.”
Zayed and his colleagues collected blood samples from 87 patients before they underwent vascular surgery to treat chronic limb-threatening ischemia.
“Preoperative fasting serum samples from 87 patients undergoing vascular intervention were collected between October 2014 and September 2016,” noted the researchers.
The team observed that cFAS levels in the blood were independently associated with the disease. They found that cFAS levels in the blood were associated with the fatty acid synthase content of plaque sampled from the femoral artery. The researchers also reported that cFAS circulates through the bloodstream while bound to LDL.
“Oftentimes, I will see patients in my practice who have high LDL but are otherwise healthy individuals—they don’t have evidence of disease in their arteries,” said Zayed, who is also a vascular surgeon at Barnes-Jewish Hospital. “We’ve scratched our heads at this. Do we put these patients on cholesterol-lowering medication? Are they still at high risk of cardiovascular disease? Our guidelines tell us to be aggressive in treating these patients. But my suspicion is the problem is not just LDL. Rather, the problem is enzymes that are attached to LDL that are conferring the cardiovascular disease that we see, particularly in the peripheral arteries, as well as the coronary arteries that deliver blood to the heart and the carotid arteries that deliver blood to the brain.”
The researchers found that LDL is more abundant than cFAS in the blood, so the key measure may not be LDL itself, but how much of the LDL is carrying cFAS along with it.
The team is investigating cFAS as a potential therapeutic target that could slow plaque buildup and help prevent cardiovascular disease.
“There are drugs that inhibit fatty acid synthase, and we’re working on evaluating new ones that are more targeted,” Zayed said. “None of them are ready for clinical trials in people for this purpose yet, but we’re using those drugs to test animal models of the disease to see if they actually decrease the buildup of plaque in the arteries. It would be wonderful to be able to practice precision vascular medicine—to tailor therapy to high-risk patients to reduce their risk of developing severe complications of cardiovascular disease.”
