Scientists at the University of Oklahoma announced on June 29 that they have identified a previously unrecognized immune system pathway that helps explain how cigarette smoking increases the risk of cardiovascular disease. The findings, published in Circulation Research, show that cigarette smoke activates immune cells, triggering widespread inflammation and accelerating plaque buildup in arteries.
Cigarette smoking is widely recognized as a major risk factor for cardiovascular disease and is associated with heart attacks, strokes, and other life-threatening conditions. While its effects on lung health are well known, the biological processes connecting cigarette smoke exposure to cardiovascular problems have been less clear.
The study was conducted using a mouse model of atherosclerosis and focused on neutrophils, which are the most abundant white blood cells responsible for responding to pathogens. Researchers found that chemicals from cigarette smoke agitate neutrophils when inhaled into the lungs, causing them to rapidly increase in number. These neutrophils then move into blood vessels where they interact with macrophages—another type of white blood cell—and die as a result. Upon their death, neutrophils release proteins such as Interleukin 1-alpha and Interleukin-1 beta, leading macrophages to become dysfunctional. When macrophages cannot remove dead cells or bad cholesterol effectively, arteries become more susceptible to plaque dislodging and clot formation—events that can cause heart attacks or strokes. Additional factors like high blood pressure can further increase vulnerability.
"Smoking essentially reprograms some of our 'first responder' immune cells," said Prabhakara Nagareddy, Ph.D., professor of medicine at the OU College of Medicine and senior author of the paper. "Instead of helping protect us, they become overactive and drive chronic inflammation inside the arteries."
The research also found that tobacco-related chemicals could trigger these inflammatory effects even when administered orally rather than inhaled. "This suggests that tobacco-related chemicals can directly activate immune cells after they are absorbed into the body," Nagareddy said. "The cardiovascular effects of tobacco exposure may extend beyond inflammation that begins in the lungs." He added, "Most therapies today focus on lowering cholesterol. That's incredibly important, but inflammation is the other half of the story... Understanding how smoking activates inflammation could eventually help us identify new treatments that protect people who are at high cardiovascular risk."
Dipanjan Chattopadhyay, Ph.D., first author and postdoctoral researcher in Nagareddy's laboratory, said: "Cigarette smoke contains more than 7,000 chemical compounds. Our next goal is to identify which ones are actually driving this harmful inflammatory response." The team plans further studies involving other nicotine delivery systems such as vaping and nicotine pouches as well as similar studies in humans.
