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עמוד בית
Sun, 08.12.24

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June 2016
Einat Hertzberg-Bigelman MsC, Rami Barashi MD, Ran Levy PhD, Lena Cohen MSc, Jeremy Ben-Shoshan MD PhD, Gad Keren MD and Michal Entin-Meer PhD

Background: Chronic kidney disease (CKD) is often accompanied by impairment of cardiac function that may lead to major cardiac events. Erythropoietin (EPO), a kidney-produced protein, was shown to be beneficial to heart function. It was suggested that reduced EPO secretion in CKD may play a role in the initiation of heart damage. 

Objectives: To investigate molecular changes in the EPO/erythropoietin receptor (EPO-R) axis in rat cardiomyocytes using a rat model for CKD.

Methods: We established a rat model for CKD by kidney resection. Cardiac tissue sections were stained with Masson’s trichrome to assess interstitial fibrosis indicating cardiac damage. To evaluate changes in the EPO/EPO-R signaling cascade in the myocardium we measured cardiac EPO and EPO-R as well as the phosphorylation levels of STAT-5, a downstream element in this cascade.

Results: At 11 weeks after resection, animals presented severe renal failure reflected by reduced creatinine clearance, elevated blood urea nitrogen and presence of anemia. Histological analysis revealed enhanced fibrosis in cardiac sections of CKD animals compared to the sham controls. Parallel to these changes, we found that although cardiac EPO levels were similar in both groups, the expression of EPO-R and the activated form of its downstream protein STAT-5 were significantly lower in CKD animals.

Conclusions: CKD results in molecular changes in the EPO/EPO-R axis. These changes may play a role in early cardiac damage observed in the cardiorenal syndrome.

 

December 2015
May-Tal Rofe MD, Ran Levi PhD, Einat Hertzberg-Bigelman MSc, Pavel Goryainov MSc, Rami Barashi MD, Jeremy Ben-Shoshan MD PhD, Gad Keren MD and Michal Entin-Meer PhD
 

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. 


 

 
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