Pathogenic Insights into the Cardiorenal Syndrome in Heart Failure (HF) with Preserved Ejection Fraction (HFpEF)

Albin Oh, MD

Albin Oh MD, Maria Valero-Munoz PhD, Flora Sam MD

Background: The lack of therapies for heart failure with preserved ejection fraction (HFpEF) suggests that identifying novel pathways is a priority. Clinical management of HF, particularly HFpEF, is challenged by concurrent renal dysfunction, known as the cardiorenal syndrome (CRS). In a murine HFpEF model, we previously demonstrated cardiac hypertrophy, fibrosis & lung congestion. We next investigated the effect of HFpEF induction in the renal phenotype.

Methods:  Uninephrectomized mice received 1% NaCl drinking water ± d-aldosterone for 4 weeks. The kidneys were collected and histology and qPCR performed.

Results: Renal hypertrophy & fibrosis were evident as shown by a 46% increase of kidney to body weight mass (P<0.0001) & a 15% increase in fibrosis in HFpEF vs. Sham (P<0.03). In parallel, mRNA fibrotic markers were also increased in the kidneys of HFpEF mice (tgf-β: 1.7-fold; col-I: 4.0-fold; col-III: 3.0-fold vs. Sham, P<0.005). These results were associated with activation of the endothelial-mesenchymal transition (endo-MT) process, showed by 1.4-, 1.7-, 1.8-, 2.6- and 2.0-fold increases in ve-cadherin, snail, fibronectin, fibroblast-specific protein 1 and vimentin renal transcripts in HFpEF vs. Sham (P<0.05).

Conclusion: This HFpEF model aptly mirrors the hallmarks of human HFpEF. Evidence of renal hypertrophy and fibrosis mimics the cardiac phenotype and activation of markers associated with Endo-MT suggests this may be a major mechanism of CRS in HFpEF. Further studies are warranted.

4 comments

  1. Albin, terrific work!! I hope you can continue this line of investigation-seems that it could be very important! Well-done! Dave

  2. This is such an important line of research Albin and I am really happy that you will be continuing on this for next year! Congratulations.

  3. nice work! I’m curious how the time courses of the renal vs cardiac phenotypes and transcriptomes compare

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