Cardiac hypertrophy and cardiac cell death in chronic kidney disease

May Tal Rofe, Ran Levi, Einat Hertzberg-Bigelman, Pavel Goryainov, Rami Barashi, Jeremy Ben-Shoshan, Gad Keren, Michal Entin-Meer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Chronic kidney disease (CKD) is a prevalent clinical condition affecting 15% of the general population. Cardiorenal syndrome (CRS) type 4 is characterized by an underlying CKD condition leading to impairment of cardiac function and increased risk for major cardiovascular events. To date, the mechanisms leading from CKD to CRS are not completely understood. In particular, it is unclear whether the pathological changes that occur in the heart in the setting of CKD involve enhanced cell death of cardiac cells. Objectives: To assess whether CKD may mediate loss of cardiac cells by apoptosis. Methods: We established rat models for CKD, acute myocardial infarction (acute MI), left ventricular dysfunction (LVD), and sham. We measured the cardiac-to-body weight as well as kidney-to-body weight ratios to validate that renal and cardiac hypertrophy occur as part of disease progression to CRS. Cardiac cells were then isolated and the percent of cell death was determined by flow cytometry following staining with annexin-FITC and propidium iodide. In addition, the levels of caspase-3-dependent apoptosis were determined by Western blot analysis using an anti-cleaved caspase-3 antibody. Results: CKD, as well as acute MI and LVD, resulted in significant cardiac hypertrophy. Nevertheless, unlike the increased levels of cell death observed in the acute MI group, in the CKD group, cardiac hypertrophy was not associated with induction of cell death of cardiac cells. Caspase-3 activity was even slightly reduced compared to sham-operated controls. Conclusions: Our data show that while CKD induces pathological changes in the heart, it does not induce cardiac cell death.

Original languageEnglish
Pages (from-to)744-749
Number of pages6
JournalIsrael Medical Association Journal
Volume17
Issue number12
StatePublished - Dec 2015

Keywords

  • Cardiac cell death
  • Cardiorenal syndrome (CRS)
  • Chronic kidney disease (CKD)
  • Cleaved caspase-3
  • Left entricular hypertrophy

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