Clinical & Experimental Cardiology
Open Access

Abstract

Renal Failure is Associated with Driving of Gene Expression towards Cardiac Hypertrophy and Reduced Mitochondrial Activity

Michal Entin-Meer, Metsada Pasmanik-Chor, Jeremy Ben-Shoshan, Sofia Maysel-Auslender, Pavel Goryainov, Ido Laron, Shelly Klipper, Varda Oron-Karni, Jonathan Semo, Einat Hertzberg and Gad Keren

Background: The clinical concomitant presentation of cardiac and renal failure (RF) has been referred to as the “cardiorenal syndrome” (CRS), whereby acute or chronic dysfunction of one organ induces acute or chronic dysfunction of the other. To improve our understanding of the cellular and molecular mechanisms underlying the development and diversification of CRS we established a model for CRS and studied the unique gene expression patterns associated with this syndrome.

Methods and Results: We have utilized a rat model in which an acute myocardial infarction (AMI) was induced on the background of subtotal nephrectomy. Changes in cardiac functions and gene expression were analyzed as detailed below. The data demonstrate that chronic RF (CRF) enhances fibrosis of the cardiac tissue. The gene chip array data detect overexpression of genes associated with hypertrophy as well as to reduced mitochondrial activity in the heart. The gene chip data also indicate that chymase inhibitors and coenzyme Q10 may be beneficial in the management of RF- induced cardiac hypertrophy. We further show that in line with the upregulation of the Ngal gene, LCN2, upon acute MI and CRS, Ngal protein levels significantly increase five days post infarction and remain stably elevated when the cardiac disease progresses to CRS.

Conclusions: Acute cardiac injury in the setting of CRF is associated with marked histological and gene expression changes in the heart. Based on our data, predictive biomarkers for the development of RF- induced cardiac hypertrophy as well as novel therapeutic directions may emerge.