White blood cell transcriptome correlates with renal function in acute heart failure.
It is notoriously difficult to classify patients with acute heart failure (AHF) because of variations in clinical presentation, different etiologies, the impact of comorbidities, and variable prognoses. In this study, we used DNA whole-genome microarrays to classify 24 patients with AHF based on the transcriptome of their peripheral blood nuclear cells. The main purpose was to verify whether any transcriptomic sub-clusters had clinical correlations. We identified two distinct groups of transcriptomic profiles that correlated with normal (1.125 mg/dL) and increased (1.783 mg/dL) mean blood creatinine concentrations. These two subgroups of patients (n = 12) differed in the expression of more than 6000 genes and 108 signaling pathways. The most significant regulated signaling pathway was the aldosterone-regulated sodium reabsorption pathway and the most significant regulated genes included the angiotensin-converting enzyme gene. This suggests that kidney impairment in patients with AHF is related to dysregulation of the renin-angiotensin-aldosterone system. The interesting findings of our study were the significant differences in expression of genes belonging to the aldosterone-regulated signaling pathway: Na+/K+transporting ATPase and NEDD4L (neuronal precursor cell expressed developmentally down-regulated 4-like) between patients with and without renal dysfunction. Future studies of blood-cell transcriptomic profiles in patients with AHF will provide further insights into the molecular pathogenesis of this cardiorenal disorder.
First Department of Cardiology, Medical University of Warsaw, Poland.
Sebastian
S
Szmit
Michal
M
Jank
Henryk
H
Maciejewski
Pawel
P
Balsam
Alicja
A
Majewska
Magdalena
M
Loj
Marcin
M
Grabowski
Krzysztof J
KJ
Filipiak
Tomasz
T
Motyl
Grzegorz
G
Opolski
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000097:blood; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007962:Leukocytes; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D051437:Renal Insufficiency / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D059467:Transcriptome / Q000235:genetics*
D017931:DNA Primers; D003404:Creatinine