Heart disease is the number one cause of death worldwide, according to the World Health Organization, but scientists still do not understand all the factors that affect heart health.

University of Louisville environmental medicine researchers are working to better understand how natural, social and personal environments affect health, particularly the cardiovascular system. In recent months, the National Institutes of Health have awarded four grants totaling $11.6 million to researchers affiliated with UofL’s Christina Lee Brown Envirome Institute to study factors affecting heart health. Through these projects, they hope to better understand how environmental exposures and tobacco products can affect the cardiovascular system, as well as how remodeling takes place in the heart after a heart attack.

“The unique and synergistic research collaborative we have built at the Envirome Institute already has resulted in new discoveries about the biological and the environmental factors that contribute to heart disease,” said Aruni Bhatnagar, chief of the UofL Division of Environmental Medicine and director of the Envirome Institute. “Our studies funded by these new grants will lead to better understanding of the causes and progression of cardiovascular disease and new ways to protect and improve cardiovascular health.”

The new projects address the cardiovascular effects of newly introduced ingredients in electronic cigarette liquids, exposure to benzene, prenatal and infant exposure to combinations of substances and their impact on sleep in adolescence and the metabolic processes occurring after a heart attack that result in scarring in the heart.

One grant provides $3.3 million to investigate how exposure to benzene affects blood vessels. Sanjay Srivastava, professor of medicine who leads the project, said preliminary research shows that benzene worsens atherosclerosis, an underlying cause of cardiovascular disease and stroke. Atherosclerosis, a buildup of fatty deposits in arteries, reduces blood flow and flexibility of the arteries. Benzene is one of the top 20 pollutants from industrial sources in the United States, primarily from gasoline refineries. Outside industrial locations, exposure is higher near gas stations and from automobile exhaust and cigarette smoke. Benzene is known to cause cancer, but this is the first study to evaluate the effects of the chemical on heart disease, especially at levels typically experienced in the environment.

Cardiac fibrosis is essential for upholding the structure of the heart after heart attack, but also tends to produce excessive scar tissue and stiffening of the heart. Bradford Hill is examining the processes behind stiffening and scarring in the heart following myocardial infarction. A $2.3 million grant is funding the professor of medicine’s work to investigate the metabolic processes underlying this process. Hill hopes the work will lead to a therapy that supports the repair process but also reduces excessive scarring, allowing heart attack patients to fare better down the road.

Clara Sears, assistant professor of environmental medicine, received a $2.1 million grant for a project to discover how exposure to mixtures of common chemicals and pollutants before birth and in infancy affects sleep health in adolescence. Ultimately, she hopes to understand whether exposures to phthalates (common components of plastics), metals and per-/polyfluoroalkyl substances (PFAS – known as “forever chemicals”) may be linked to cardiovascular issues later in life.

The largest of the grants, $3.9 million, will fund research into potential toxicity of new synthetic cooling compounds that are being used in electronic cigarette liquids. Daniel J. Conklin leads the project to learn whether these compounds are harmful to the cardiovascular and pulmonary systems when heated and inhaled. The compounds mimic the cooling effect of menthol, which can be irritating in high doses, but they have not been tested for safety or toxicity as inhaled substances. For this new project, Conklin, a professor of medicine who has studied the cardiovascular effects of e-cigarette and cigarette components for more than two decades, is testing the effects of the new constituents as well as documenting the impact of dual use – smoking conventional cigarettes along with vaping. The Food and Drug Administration’s Center for Tobacco Products will use the results of these studies to determine potential recommendations to regulate the products’ use.

“We are going to address the issue of dual use, where there are both cigarettes and e-cigarettes in use, because this is a very common phenomenon and the signals are coming that it’s actually worse than either one alone,” Conklin said.