Source: American Heart Association
The results of a new mouse model may help to understand how depression and prolonged and severe stress increase the risk of cardiovascular disease, according to preliminary research presented to the American Heart Association’s Vascular Discovery: From Genes to Medicine Scientific Sessions 2022.
“Previous research has shown that major depressive disorders and anxiety due to prolonged and severe stress have been associated with an increase in the rate of cardiovascular disease. The risk of developing cardiovascular disease increases in proportion to the severity. of depression, ”said study lead author Özlem Tufanli Kireccibasi, Ph.D., postdoctoral fellow in the laboratory of Edward A. Fisher, MD, Ph.D., MPH, FAHA, Research Center Cardiovascular from the NYU Grossman School of Medicine in New York City.
“When there is both a major depressive disorder and a cardiovascular disease, the prognosis is worse for both conditions.”
Researchers say theirs is the first study to use a mouse model of chronic stress and depression to investigate whether and how chronic stress can affect cholesterol-lowering medications.
The researchers examined mice that lacked a low-density lipoprotein (LDLr) receptor, which is needed to remove LDL (bad) cholesterol from the body. These mice, like people born without the receptor, are prone to developing accumulations of fat called plaque in their arteries and are prone to premature and aggressive cardiovascular disease.
Unstable plaque (prone to rupture) can rupture causing blood clots to form that block blood flow, which can lead to a heart attack or stroke. To mimic the development of plaque in people, the mice were fed a high-cholesterol diet for 24 weeks.
Half of the mice were exposed to social stress by sharing their living space with other larger, more aggressive mice for short periods of time for ten days. After each episode of stress, mice were evaluated for social avoidance and behaviors similar to depression or anxiety.
The mice that showed the behaviors were classified as susceptible (depressed) and the others were classified as resilient (effective coping). The other half of the mice (controls) were not exposed to social stress.
Both susceptible (depressed) and control mice were treated with a drug that lowers LDL for 3 weeks, to mimic the treatment of cholesterol in humans. Previous studies have found that when LDLr-deficient mice are treated with lipid-lowering drugs, the arterial plaque becomes less inflammatory and more stable.
After treatment, the mice were tested for changes in the number of inflammatory cells in their plaque, the number of inflammatory white blood cells (monocytes) circulating in the blood, and the number of bone marrow cells. , which are precursors of abundant immune cells. on plate.
Resistant mice were evaluated similarly, however, analyzes of this group of mice are ongoing.
The analyzes found that, compared to mice not exposed to stress (the control group), susceptible (depressed) mice from the group exposed to social stress had:
- 50% greater increase in immune cells within the plaque of their arteries;
- double the number of circulating monocytes, which are precursors of inflammatory cells;
- 80% increase in the number of immune cell precursors in the bone marrow;
- less collagen inside the artery plate, which is an indicator of instability; i
- a similar reduction in lipid levels compared to the response of control groups to medication that lowers LDL.
“The main finding is that repeated stress and the physiological and behavioral effects of hostile interactions (social defeat) appear to prevent complete beneficial changes in plaques that should be induced by lipid-lowering drugs,” said Tufanli Kireccibasi.
The researchers also looked at whether differences in the bone marrow of depressed mice may be the basis for differences in plaque size and characteristics.
To test this, another group of LDLr-deficient mice received a bone marrow transplant from susceptible (depressed) mice or the control group.
After the bone marrow transplant, the mice were fed the high-cholesterol diet for 24 weeks.
Compared to mice that received bone marrow from the control group (no stress), mice that received bone marrow from the susceptible group had:
- 16% greater increase in immune cell precursors in bone marrow;
- 50% greater increase in inflammatory monocytes in the blood; i
- no change in the size of the plaque, but in the composition of the plaque, with 23% more inflammation inside the plaques.
“With all our results together, we suggest that in situations where there is chronic stress, the adverse effects of high cholesterol can be improved and the benefits of low cholesterol reduced.
“This suggests that chronic stress mediates genetic reprogramming, called epigenetic changes, in the bone marrow precursors of monocytes, so that when cells enter the plaques they are already more inflammatory,” he said. dir Tufanli Kireccibasi.
This mouse model can provide a way to research and improve the treatment of depression and prolonged stress and, in turn, improve cardiovascular outcomes.
“These findings may indicate that more mental health care is needed to combat cardiovascular disease, especially for people with depression or chronic stress. In the coming decades, new therapies for atherosclerosis should focus on altering immune responses, inhibit inflammation and promote plaque resolution pathways.
“These therapies have great potential to benefit people with cardiovascular disease, and probably especially those with depression,” said Tufanli Kireccibasi.
Researchers are currently collecting samples from mice that were exposed to the same repeated stress but appeared to be resistant.
“We will do the same analyzes as this study to determine if it is exposure to or susceptibility to stress that causes plaque changes that lead to a decrease or worsening of plaque,” said Tufanli Kireccibasi.
Co-authors are Bianca Scolaro, Ph.D .; Ada Weinstock, Ph.D .; Angelica Torres Berrio, Ph.D .; Eric Parise, Ph.D .; Flurin Cathomas, MD; Kenny Chan, Ph.D .; Eric J. Nestler, MD, Ph.D .; Scott J. Russo, Ph.D .; and Edward A. Fisher, MD, Ph.D., MPH, FAHA. The authors’ disclosures are listed in the summary.
About this research news on mental health and heart disease
Author: Press Office
Source: American Heart Association
Contact: Press Office – American Heart Association
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Original research: The findings will be presented at the American Heart Association’s Vascular Discovery: From Genes to Medicine Scientific Sessions 2022