Summary: Mouse study reveals how depression and chronic stress can have an impact on cholesterol-lowering medications and influence the risk of heart disease.

Results from a new mouse model may aid in understanding how depression and prolonged and severe stress increase the risk of cardiovascular disease, according to preliminary research presented at the American Heart Association’s Vascular Discovery: From Genes to Medicine Scientific Sessions 2022.

“Previous research has shown major depressive disorders and anxiety due to prolonged and severe stress have been associated with an increased rate of cardiovascular disease.

The risk of developing cardiovascular disease increases in proportion to depression severity,” said lead study author Özlem Tufanli Kireccibasi, Ph.D., a postdoctoral fellow in the laboratory of Edward A.

Fisher, M.D., Ph.D., M.P.H., FAHA, in the Cardiovascular Research Center at NYU Grossman School of Medicine in New York City.

These mice, like people who are born lacking the receptor, are prone to develop fatty buildups called plaque in their arteries and are subject to premature and aggressive cardiovascular disease.

The other half of the mice (controls) were not exposed to social stress.

Both the susceptible (depressed) mice and the control mice were treated with an LDL-lowering medication for 3 weeks, to mimic cholesterol treatment in humans.

The analyses found that, compared with mice not exposed to stress (the control group), the susceptible (depressed) mice from the group exposed to social stress had:.

To test this, another group of LDLr-deficient mice received bone marrow transplanted from either the susceptible (depressed) mice or the control group.

Compared with mice that received bone marrow from the control group (no stress), the mice that received bone marrow from the susceptible group had:.

“This suggests that chronic stress mediates reprogramming at the genetic level, called epigenetic changes, in bone marrow precursors of monocytes so that when the cells enter plaques they are already more inflammatory,” Tufanli Kireccibasi said.

This mouse model may provide a way to investigate and improve treatment for depression and prolonged stress and, in turn, improve cardiovascular outcomes.

“These findings may indicate more attention to mental health is needed to fight cardiovascular disease, particularly for people with depression or chronic stress.

The researchers are currently collecting samples from mice that were exposed to the same repeated stress but appeared to be resilient to it.