Early activation of deleterious molecular pathways in the kidney in experimental heart failure with atrial remodeling

Tomoko Ichiki, Brenda K. Huntley, Gail J. Harty, S Jeson Sangaralingham, John C Jr. Burnett

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Heart failure (HF) is a major health problem with worsening outcomes when renal impairment is present. Therapeutics for early phase HF may be effective for cardiorenal protection, however the detailed characteristics of the kidney in early-stage HF (ES-HF), and therefore treatment for potential renal protection, are poorly defined. We sought to determine the gene and protein expression profiles of specific maladaptive pathways of ES-HF in the kidney and heart. Experimental canine ES-HF, characterized by de-novo HF with atrial remodeling but not ventricular fibrosis, was induced by right ventricular pacing for 10 days. Kidney cortex (KC), medulla (KM), left ventricle (LV), and left atrial (LA) tissues from ES-HF versus normal canines (n = 4 of each) were analyzed using RT-PCR microarrays and protein assays to assess genes and proteins related to inflammation, renal injury, apoptosis, and fibrosis. ES-HF was characterized by increased circulating natriuretic peptides and components of the renin-angiotensin-aldosterone system and decreased sodium and water excretion with mild renal injury and up-regulation of CNP and renin genes in the kidney. Compared to normals, widespread genes, especially genes of the inflammatory pathways, were up-regulated in KC similar to increases seen in LA. Protein expressions related to inflammatory cytokines were also augmented in the KC. Gene and protein changes were less prominent in the LV and KM. The ES-HF displayed mild renal injury with widespread gene changes and increased inflammatory cytokines. These changes may provide important clues into the pathophysiology of ES-HF and for therapeutic molecular targets in the kidney of ES-HF.

Original languageEnglish (US)
Article numbere13283
JournalPhysiological Reports
Volume5
Issue number9
DOIs
StatePublished - May 1 2017

Fingerprint

Atrial Remodeling
Heart Failure
Kidney
Kidney Cortex
Genes
Heart Ventricles
Canidae
Wounds and Injuries
Proteins
Fibrosis
Kidney Medulla
Cytokines
Protein Array Analysis
Natriuretic Peptides
Renin-Angiotensin System
Transcriptome
Renin
Up-Regulation
Sodium
Apoptosis

Keywords

  • Heart failure
  • inflammation
  • kidney
  • natriuretic peptides

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Early activation of deleterious molecular pathways in the kidney in experimental heart failure with atrial remodeling. / Ichiki, Tomoko; Huntley, Brenda K.; Harty, Gail J.; Sangaralingham, S Jeson; Burnett, John C Jr.

In: Physiological Reports, Vol. 5, No. 9, e13283, 01.05.2017.

Research output: Contribution to journalArticle

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