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Cardiorenal disease connection during post-menopause: The protective role of estrogen in uremic toxins induced

Jiayi Pei1, Magdalena Harakalova2, Hester den Ruijter3

  • 1Department of Nephrology and Hypertension, Division of Internal Medicine and Dermatology, University Medical Center Utrecht, The Netherlands.

International Journal of Cardiology
|March 26, 2017
PubMed

Insights

Estradiol (E2) may protect against heart failure with preserved ejection fraction (HFpEF) by counteracting harmful effects of uremic toxins (UTs) in chronic kidney disease (CKD). This involves reducing inflammation and improving blood clotting in post-menopausal women.

Area of Science:

  • Cardiovascular Research
  • Nephrology
  • Endocrinology

Background:

  • Heart failure with preserved ejection fraction (HFpEF) is linked to female gender, post-menopause, and chronic kidney disease (CKD).
  • CKD involves elevated uremic toxins (UTs) and hormonal changes, potentially causing coronary microvascular endothelial dysfunction in HFpEF.
  • Understanding the interplay of these factors is crucial for identifying new therapeutic targets for HFpEF.

Purpose of the Study:

  • To review the protective role of estradiol (E2) in CKD-associated microvascular disease and HFpEF.
  • To investigate the molecular mechanisms underlying the interaction between UTs, menopausal hormonal changes, and endothelial function.

Main Methods:

  • Analysis of publicly available transcriptome datasets (NCBI Gene Expression Omnibus).
  • Inclusion of data from human endothelial cells treated with indoxyl sulfate (IS), high inorganic phosphate (HP), or E2.
  • Comprehensive in silico analysis and literature review of gene expression data.

Main Results:

  • Significant overlap in gene expression patterns induced by UTs (IS/HP) and E2.
  • UTs (HP and/or IS) altered the expression of 188 genes (upregulated) and 572 genes (downregulated) compared to E2 treatment.
  • 36 genes were commonly affected by both IS and HP.

Conclusions:

  • CKD-induced UTs negatively impact renal and cardiac endothelial homeostasis, promoting inflammation and angiogenesis dysregulation.
  • E2 demonstrates a protective effect by inhibiting UTs-induced inflammation.
  • E2 ameliorates UTs-related bleeding and thrombotic issues by restoring endothelial coagulation capacity and hemostasis.

Keywords:
Cardiorenal syndromeEstrogenHigh phosphateIndoxyl sulfateMenopauseMicrovascular dysfunction

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