3D model of Dr. Matthew Bramlett’s heart. Credit: NIH

The results of the new mouse model may help to understand how depression and prolonged and severe stress increase the risk of cardiovascular disease, according to previous research presented at scientific sessions of the American Heart Association: From Genes to Medicine. Scientific sessions of 2022. On May 12-14, 2022, Seattle will host a major global exchange of the latest advances in new and new research in atherosclerosis, thrombosis, vascular biology, peripheral vascular disease, vascular surgery, and functional genomics.

“Previous studies have shown severe depressive disorders and anxiety due to prolonged and severe stress were associated with increased speed Cardiovascular disease. The risk of developing cardiovascular disease increases in proportion to the severity of depression, ”said lead author Ozlem Tufanli Kirechibazi, Ph.D., Ph.D. Grossman School of New York in New York. “If both major depressive disorder and cardiovascular disease are present, the prognosis is worse for both diseases.”

The researchers say this 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 drugs.

The researchers studied mice that lack the low-density lipoprotein (LDL) receptor, which is needed to remove LDL (bad) cholesterol from the body. These mice, like people born without a receptor, are prone to the formation of fatty deposits called plaques in the arteries, and are prone to premature and aggressive cardiovascular disease. Unstable plaque (prone to rupture) may fall apart blood clots to form this blockage of blood flow, which can lead to a heart attack or stroke. To mimic the development of fat plaques in humans, mice were fed a high-cholesterol diet for 24 weeks.

Half of the mice were exposed social stress through sharing their living space with other large, aggressive mice for short periods of time for ten days. After each episode of stress, mice were evaluated for avoidance of social activities and behaviors similar to depression or anxiety. Mice that showed behavior were classified as susceptible (depressed) and others were classified as resilient (effective coping). The other half of the mice (control) were not exposed to social stress.

Both susceptible (depressed) mice and control mice were treated with LDL-lowering drugs for 3 weeks to mimic cholesterol treatment in humans. Previous studies have shown that when LDL-deficient mice are treated with lipid-lowering drugs, arterial plaques become less inflammatory and more stable. After treatment, mice were tested for changes in the number of inflammatory cells in their plaques, the number of inflammatory white blood cells (monocytes) circulating in the blood, and the number of bone marrow cells that are precursors. immune cells rich in plaque. Resistant mice were evaluated in a similar manner, however, analyzes for this group of mice are ongoing.

The analysis found that compared to mice that were not exposed to stress ( control group), sensitive (depressed) mice from the group under social stress had:

  • 50% higher growth of immune cells in plaques in their arteries;
  • double the number of circulating monocytes that are precursors of inflammatory cells;
  • 80% increase in the number of precursors of immune cells in the bone marrow;
  • less collagen in plaques in the arteries, which is an indicator of instability; and
  • a similar decrease in lipid levels compared with the response of control groups to drugs that reduce LDL.

“The main conclusion is that repeated stress and the physiological and behavioral effects of hostile interactions (social defeat) appear to prevent the full beneficial changes of plaques that should be caused by lipid-lowering drugs,” said Tufanli Kirechibazi.

The researchers also analyzed whether differences in the bone marrow of depressed mice underlie 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 a control group. After bone marrow transplantmice were fed a high-cholesterol diet for 24 weeks.

Compared with 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 precursor cells in bone marrow;
  • 50% greater growth of inflammatory monocytes in the blood; and
  • without changing the size of the plaque, but in the composition of the plaque, with inflammation inside the plaque by 23% more.

“Taking all our results together, we believe that in situations where there is chronic stress, the adverse effects of high cholesterol may increase and the benefits of low cholesterol decrease. This suggests that chronic stress will mediate reprogramming at the genetic level, called epipe. , art bone marrow precursors of monocytes, so when cells get into plaques, they are already more inflammatory, ”said Tufanli Kirechibazi.

This mouse model can provide a way to investigate and improve the treatment of depression and prolonged stress and in turn improve cardiovascular outcomes.

“These findings may suggest that more attention to mental health is needed to combat cardiovascular disease, especially for people with depression or chronic stress. In the coming decades, new treatments for atherosclerosis should aim to alter immune responses, inhibit inflammation, and stimulate plaque elimination pathways. These treatments have great potential to benefit people with cardiovascular disease, and probably especially those who suffer from depression, ”said Tufanli Kirechibazi.

Researchers are currently collecting samples from mice who were subjected to the same repeated stress, but proved to be resistant to it. “We will conduct the same analysis as in this study to determine whether stress exposure or sensitivity to it is causing changes in plaque that lead to a reduction or deterioration plaque“- said Tufanli Kirechibazi.

Co-authors – Bianca Scalara, PhD; Ada Weinstack, PhD; Angelica Torres Berio, PhD; Eric Paris, PhD; Flurin Katomas, MD; Kenny Chan, Ph.D.; Eric J. Nestler, MD, PhD; Scott J. Rousseau, Doctor of Philosophy; and Edward A. Fisher, MD, PhD, MPH, FAHA. The disclosures of the authors are given in the abstract.

Researchers are revealing new details of inflammation that contributes to heart disease

Additional information:
professional.heart.org/en/meet cient -scientific-sessions

Citation: Links linking stress, depression and heart disease risk found in a mouse model (2022, May 13), obtained May 13, 2022 from https://medicalxpress.com/news/2022-05-links-stress -depression-heart-disease.html

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