A common, safe and inexpensive drug for type 2 diabetes, metformin decreases the risk of heart attacks and strokes triggered by air pollution by reducing inflammation in the lungs that triggers clotting, according to a new Northwestern Medicine study in human lung tissue and an animal model, published in Cell Metabolism.
Metformin flips a switch in immune cells that reside in the lung and continuously sample the air we breathe. It prevents those immune cells, macrophages, from releasing dangerous molecules into the blood that promote heart attacks and strokes after pollution exposure.
“These findings suggest metformin as a potential therapy to prevent some of the premature deaths attributable to air pollution exposure worldwide,” said co-lead study author Dr. Scott Budinger, the Ernest S. Bazley Professor of Airway Diseases and chief of Pulmonary and Critical Care in the Department of Medicine. Dr. Budinger is also a Northwestern Medicine pulmonary and critical care physician and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
More than 100 million people take metformin worldwide.
The drug works by targeting the mitochondria — the cell’s energy center — in lung macrophages. When air pollution particles get into the lungs, the mitochondria release hydrogen peroxide that promotes inflammation and clotting. Metformin slows down the mitochondria and the release of hydrogen peroxide.
“The simplest next step would be to validate our study with metformin in people in China or other places where exposure to high levels of air pollution are common to see if it reduces inflammation,” Dr. Budinger said.
Dr. Gökhan Mutlu, chief of pulmonary and critical care medicine at University of Chicago Medicine, is also a co-lead investigator.
Air pollution remains an enormous U.S. public health problem, causing thousands of excess deaths in the Medicare population alone each year. The large majority of these deaths are due to heart attacks and strokes.
Because air pollution levels are about 10 times higher in China, India and other parts of the developing world compared to the U.S., the global health impact of air pollution is much larger, Dr. Budinger noted.
In the study, a pediatric formulation of metformin was given to mice in their drinking water for three days. It was an equivalent concentration to the dose people take for diabetes. Mice were exposed to air pollution from Chicago in a specially designed chamber that concentrates the particles to levels similar to those seen in China.
When mice were exposed to air pollution in the laboratory, their macrophages released an inflammatory molecule called IL-6, which has been linked to heart attacks and strokes. Metformin prevented the release of IL-6 and reduced the speed at which clots formed after an injury. The same findings were seen in lung macrophages from humans.
The findings are a result of Dr. Budinger’s more than 20-year collaboration with Dr. Navdeep Chandel, the David W. Cugell, MD, Professor of Medicine in the division of pulmonary and critical care, who studies metformin and its effects on mitochondrial metabolism.