New Studies Link SSRI Treatment and Serum Magnesium to Improved Endothelial Dysfunction

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Int J Cardiol. 2016 Aug 8;223:176-181

Transl Psychiatry. 2016 Sep 6;6(9):e886. doi: 10.1038/tp.2016.156.

Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model.

Lopez-Vilchez I1Diaz-Ricart M1Navarro V2Torramade S1Zamorano-Leon J3Lopez-Farre A3Galan AM1Gasto C2Escolar G1.

1Department of Hemotherapy and Hemostasis, Hospital Clinic of Barcelona, Biomedical Diagnosis Centre, Institute of Biomedical Research August Pi i Sunyer, University of Barcelona, Barcelona, Spain.

2Department of Psychiatry, Hospital Clinic of Barcelona, Institute Clinic of Neurosciences, Barcelona, Spain.

3Department of Medicine, School of Medicine, Complutense University, Madrid, Spain.

Abstract

There is a link between depression, cardiovascular events and inflammation. We have explored this connection through endothelial dysfunction, using in vivo and in vitro approaches. We evaluated circulating biomarkers of endothelial dysfunction in patients with major depression at their diagnosis (MD-0) and during antidepressant treatment with the selective serotonin reuptake inhibitor escitalopram, for 8 and 24 weeks (MD-8 and MD-24). Results were always compared with matched healthy controls (CON). We measured in vivo circulating endothelial cells (CECs) andendothelial progenitor cells (EPCs) in blood samples, and assessed plasma levels of soluble von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1). CEC counts, soluble VWF and VCAM-1 were statistically elevated in MD-0 (P 0.01 versus CON) and gradually decreased during treatment. Conversely, EPC levels were lower in MD-0, tending to increase throughout treatment. In vitro studies were performed in human endothelial cells cultured in the presence of sera from each study group. Elevated expression of the inflammation marker intercellular adhesion molecule-1 and oxidative stress, with lower presence of endothelial nitric oxide synthase and higher reactive oxygen species production, were found in cells exposed to MD-0 sera (P 0.05 versus CON). These results were normalized in cells exposed to MD-24 sera. Thrombogenicity of extracellular matrices generated by these cells, measured as expression of VWF, tissue factor and platelet reactivity, showed non-significant differences. We provide a model of cultured endothelial cells reproducing endothelial dysfunction in naive patients with major depression, demonstrating endothelial damage and inflammation at diagnosis, and recovering with selective serotonin reuptake inhibitor treatment for 24 weeks.

CONCLUSION:

We provide a model of cultured endothelial cells reproducing endothelial dysfunction in naive patients with major depression, demonstrating endothelial damage and inflammation at diagnosis, and recovering with selective serotonin reuptake inhibitor treatment for 24 weeks.

Yonsei Med J. 2016 Nov;57(6):1446-53. doi: 10.3349/ymj.2016.57.6.1446.

The Relationship between Magnesium and Endothelial Function in End-Stage Renal Disease Patients on Hemodialysis.

Lee S1Ryu JH1Kim SJ1Ryu DR1Kang DH1Choi KB2.

  • 1Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Korea.
  • 2Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Korea. kbchoi@ewha.ac.kr.

Chronic kidney disease (CKD) patients tend to have higher serum magnesium values than healthy population due to their positive balance of magnesium in kidney. Recent studies found that magnesium level is positively correlated with endothelial function. Therefore, this study was conducted to define the relationship between magnesium level and endothelial dysfunction in end stage renal disease (ESRD) patients on hemodialysis (HD). A total of 27 patients were included in this cross-sectional study. Iontophoresis with laser-Doppler flowmetry, flow mediated dilation (FMD), and carotid intima-media thickness were measured. Patients’ average serum magnesium levels were measuredover previous three months, including the examination month. Pearson’s correlation coefficient analysis and multivariate regression model were used to define the association between magnesium and endothelial function. In the univariate analysis, higher magnesium levels were associated with better endothelium-dependent vasodilation (EDV) of the FMD in ESRD patients on HD (r=0.516, p=0.007). When the participants were divided into two groups according to the median magnesium level (3.47 mg/dL), there was a significant difference in EDV of FMD (less than 3.47 mg/dL, 2.8±1.7%; more than 3.47 mg/dL, 5.1±2.0%, p=0.004). In multivariate analysis, magnesium and albumin were identified as independent factors for FMD (β=1.794, p=0.030 for serum magnesium; β=3.642, p=0.012 for albumin).

CONCLUSION:

This study demonstrated that higher serum magnesium level may be associated with better endothelial function in ESRD patients on HD. In the future, a large, prospective study is needed to elucidate optimal range of serum magnesium levels in ESRD on HD patients.

 

 

 

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