Genetic Links Between Depression and Heart Disease in Women
Shira Peretz1, Marina Kurtz1, Aviad Sivan1
1Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
Insights
Young women with depression show genetic markers for increased cardiovascular disease (CVD) risk. Their bodies have a reduced ability to repair blood vessels, accelerating atherosclerosis.
Area of Science:
- Cardiovascular Research
- Genetics
- Psychiatry
Background:
- Cardiovascular disease (CVD) is uncommon in premenopausal women, yet depression increases CVD prevalence.
- Depression is linked to endothelial dysfunction and impaired endothelial progenitor cell (EPC) regeneration.
Purpose of the Study:
- To investigate the association between depression and CVD in young women.
- To identify genetic differences in premenopausal women with and without depression.
Main Methods:
- RNA sequencing was performed on peripheral blood samples from 30 premenopausal women with major depression and 28 controls.
- Gene expression profiles were analyzed to identify differences between the groups.
Main Results:
- 6540 differentially expressed genes were found, with 5577 downregulated and 963 upregulated.
- Key genes for EPCs and vascular regeneration (CD144, CD146, CD133) were significantly decreased.
- Genes promoting atherogenesis and thrombogenesis (CD31, CD45) were significantly increased.
Conclusions:
- Premenopausal women with depression exhibit impaired endothelial progenitor cell (CFU-EPC) growth.
- Genetic vulnerability to CVD in depressed young women stems from downregulated vascular regeneration genes and upregulated platelet/T lymphocyte activation genes.
- These genetic changes accelerate atherosclerotic and atherothrombotic pathways.
Background:
Cardiovascular disease (CVD) events are rare in premenopausal women. Nevertheless, women with depression have a higher prevalence of CVD. Patients with depression present with endothelial dysfunction and impaired ability to regenerate endothelial progenitor cells (EPCs).
Objectives:
To understand the association between depression and CVD, especially in young women.
Methods:
We collected peripheral blood samples from 30 premenopausal women diagnosed with major depression and 28 aged-matched healthy women. From these blood samples, we extracted RNA and conducted RNA sequencing to obtain comprehensive gene expression profiles. Gene expression analysis was performed to identify differences between the two groups.
Results:
We detected 6540 differentially expressed genes between the two groups, of which 5577 were downregulated and 963 up regulated. Of these genes, we detected a significant decrease of CD144 (VE-Cadherin) (P = 0.0001), CD146 (MCAM) (P = 0.0001) and CD133 (PROM1) (P = 0.00009), all known to enhance EPCs and regeneration of damaged blood vessels. A significant increase was found in the expression of CD31 (PECAM1) (P = 0.0003) and CD45 (PTPRC) (P = 0.00001), both known to promote atherogenesis and thrombogenesis with platelet and T lymphocyte activation.
Conclusions:
Young premenopausal women with depression had an impaired ability to grow colony forming units of endothelial progenitor cells (CFU-EPCs). Young women with depression are more vulnerable genetically to develop CVD because of the downregulated genes of the stem cells endothelial vascular regeneration and upregulation of genes coding for platelet and T lymphocyte activation, thus accelerating the atherosclerotic and atherothrombotic pathway.
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