Summary: A study of mice shows how depression and chronic stress affect cholesterol-lowering drugs and the risk of heart disease.
A source: American Heart Association
The results of the new mouse model will help to understand how depression and prolonged and severe stress increase the risk of cardiovascular disease, according to a preliminary study presented at the American Heart Association’s Vascular Discovery: Gene to Medicine 2022 scientific session.
“Previous research has shown that major depressive disorders and anxiety caused by prolonged and severe stress are associated with cardiovascular disease. The risk of cardiovascular disease increases with the severity of depression, ”said Dr. Edward A., the study’s lead author. Post-doctoral student in Fisher’s lab, MD, MPH, FAHA, at the Cardiovascular Research Center of the NYU Grossman School of Medicine in New York.
“When there are major depressive disorders and cardiovascular disease, the prognosis for both conditions is worse.”
The first study used a mouse model of chronic stress and depression to study the effects of chronic stress on cholesterol-lowering drugs and the effects of chronic stress, the researchers said.
The researchers found that mice lacked the low-density lipoprotein receptor (LDL) needed to clear LDL (bad) cholesterol from the body. These mice, like those born without receptors, tend to accumulate fat in their arteries, called plaques, and suffer from early and aggressive cardiovascular disease.
An unstable plaque (about to explode) can rupture, causing blood to clot, blocking blood flow, and leading to a heart attack or stroke. To mimic human fatty plaques, mice were fed a cholesterol-rich diet for 24 weeks.
Half of the mice were exposed to social stress for a short period of ten days by sharing their living space with other larger, more aggressive mice. After each stress episode, mice were evaluated for social avoidance and behaviors such as depression or anxiety.
Mice that exhibited behavior were classified as sensitive (depressed), while others were classified as resilient (effective fighting). The remaining half of the mice (controls) were not exposed to social stress.
Sensitive (depressed) mice and control mice were treated with LDL-lowering drugs for 3 weeks, mimicking the treatment of cholesterol in humans. Previous studies have shown that when LDLr-deficient mice are treated with lipid-lowering drugs, the arterial plaque becomes less inflamed and more stable.
After treatment, mice were tested for changes in the number of inflammatory cells in the plaque, the number of inflammatory leukocytes (monocytes) circulating in the blood, and the number of bone marrow cells, which are precursors of abundant immune cells. on a plate.
Stable mice were similarly evaluated, but analyzes for this group of mice are ongoing.
Analyzes compared the non-stressed mice (control group) with the social (stress) group of sensitive (depressed) mice:
- 50% growth of immune cells within the plaque in their arteries;
- doubling the number of circulating monocytes, which are precursors of inflammatory cells;
- 80% increase in the number of immune-cell precursors in the bone marrow;
- low collagen in plaque arteries, this indicator of instability; and the
- A similar decrease in lipid levels compared with the response of control groups to LDL-lowering drugs.
“The main finding is that the physiological and behavioral effects of repetitive stress and hostile interactions (social defeat) appear to prevent complete beneficial changes in plaques caused by lipid-lowering drugs,” Tufanli Kireccibasi said.
The researchers also looked at whether differences in the bone marrow of depressed mice could be the basis for differences in plate size and characteristics.
To test this, another group of mice with insufficient LDLr received bone marrow transplants from sensitive (depressed) mice or a control group.
After the bone marrow transplant, the mice were fed a cholesterol-rich diet for 24 weeks.
Compared to mice that received bone marrow from the control group (without stress), mice that received bone marrow from the susceptible group had:
- a 16% increase in immune-cell precursors in the bone marrow;
- more than 50% increase in inflammatory monocytes in the blood; and the
- There is no change in the size of the plate, but in the composition of the plates, 23% more inflammation within the plaques.
“Taking all our results together, we suggest that the negative effects of high cholesterol may increase in situations of chronic stress, while the benefits of low cholesterol may decrease.
“This chronic stress is called epigenetic changes at the genetic level, causing reprogramming in the precursors of bone marrow monocytes, so when cells enter platelets, they may already be inflamed,” Tufanli Kirechchibasi said.
This mouse model can be studied and provided as a way to improve treatment for depression and prolonged stress and, in turn, improve cardiovascular outcomes.
“These findings suggest that more attention needs to be paid to mental health to combat cardiovascular disease, especially for people with depression or chronic stress. need to.
“This therapy is beneficial for people with cardiovascular disease, especially those with depression,” said Tufanli Kirechchibasi.
Researchers are currently collecting samples from mice that have experienced the same recurrent stress but appear to be resistant to it.
Tufanli Kirechchibasi: “We do the same analysis as this study to determine whether it is stressed or susceptible to plaque changes, which can cause it to shrink or deteriorate.”
Co-authors Bianca Scolaro, Ph.D .; Ada Weinstock, Candidate of Medical Sciences; Angelica Torres Berrio, Ph.D .; Eric Paris, Ph.D .; Flurin Katomas, MD; Kenny Chan, Ph.D. Eric J. Nestler, Ph.D. Scott J. Rousseau, Candidate of Medical Sciences; and Edward A. Fisher, MD, Ph.D., MPH, FAHA. The statements of the authors are given in the annotation.
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Author: Press service
A source: American Heart Association
The connection: The Press Service is the American Heart Association
Photo: Image in public domain
Original study: The research will be presented in 2022 at the American Heart Association’s Blood Discovery: From Genes to Medicine scientific sessions.