Abstract 12647: Widespread Activation of Kidney Injury and Remodeling Molecular Pathways in Experimental Heart Failure in Canines
Introduction: Heart failure (HF) is a major health problem with even worse prognosis in the presence of renal impairment. This cardio-renal connection in HF may suggest the necessity for dual targeting treatments in HF. We sought to determine the gene expression profiles to establish that the kidney is a target organ for widespread molecular changes in HF.
Hypothesis: Fibrotic, inflammatory, and apoptotic genes will be affected in kidney as well as the heart in experimental HF.
Methods: Experimental HF was induced in canines by rapid right ventricular pacing at 240 bpm for 10 days. Kidney cortex (KC) and medulla (KM) as well as left ventricle (LV),and left atrial (LA), tissues from normal and HF canines (n=4 of each) were analyzed using RT-PCR microarrays related to fibrosis, growth and neurohumoral factors, inflammation, apoptosis, cardiac hypertrophy and renal injury.
Results: Experimental HF was characterized by increased pulmonary arterial pressure and pulmonary capillary wedge pressure and decreased %EF with increased circulating ANP, BNP, cGMP and aldosterone levels. The weight of total heart, LV, and kidney did not change, but LA weight increased significantly. Compared to normals, 68 genes (61/7) in KC and 35 genes (32/3) in KM were changed in the kidney while in the heart 36 genes (31 up-/5 down-regulated) in LV and 106 genes (102/4) in LA were altered. . Inflammatory genes were most up-regulated in the KC (47%) while fibrotic genes were most up-regulated in LA (71%). The >10 fold up-regulated genes in the in KC were IL6, LIF, CCL2, SERPINE1, VCAM1, BIRC3, IL8, ICAM1 and SELE while in the LA were COL1A1, COL3A1, TIMP1, IFNG, IL6, LIF, CCL2, CSF3, SERPINE1, CSF3, IL1B, VCAM1, BIRC3, and OSM. Importantly, genes related to renal injury were up-regulated in both KC and KM.
Conclusions: Experimental HF was characterized by up-regulation of fibrotic, inflammatory, hypertrophic, and apoptotic genes globally in the heart and kidney, but inflammatory genes in the KC and fibrotic and inflammatory genes in LA were particularly affected. These data suggest targeted cardiorenal therapies, especially treatment for pathways of renal injury directed towards the kidney and of fibrosis directed towards the heart may be beneficial in the treatment of HF.
Author Disclosures: T. Ichiki: None. B.K. Huntley: None. S. Sangaralingham: None. G.J. Harty: None. J.C. Burnett: None.
This research has received full or partial funding support from the American Heart Association
- © 2014 by American Heart Association, Inc.