Description
The early events that signal renal dysfunction in presymptomatic heart failure are unclear. To evaluate this, we performed RNA-seq on kidneys from transgenic mice with cardiac-specific overexpression of mutant alpha-B-crystallin, which develop slowly progressive cardiomyopathy. Presymptomatic transgenic mice display an increase in serum creatinine and in urinary neutrophil gelatinase-associated lipocalin (NGAL), but lack chronic interstitial fibrosis. Presymptomatic transgenic mouse kidneys exhibited a worsened response to ischemia-reperfusion injury based on serum creatinine, urine NGAL, tubule dilation and cast score, and apoptosis. Our findings demonstrate functional renal impairment, urinary biomarker elevations, and gene expression changes that occur in early presymptomatic heart failure, which dramatically increase the susceptibility to subsequent acute kidney injury.
Overall Design
mRNA profiles were generated by performing RNA-seq on adult kidney tissue from transgenic mice (FVB/N mice that overexpress CryAB containing the R120G missense mutation driven by the cardiomyocyte-specific -myosin heavy chain promoter. We performed analysis in triplicate of kidneys from transgenic animals (prior to the onset of heart failure) vs. age-matched, sex-matched (male) control mice by deep sequencing using Illumina Hi-Seq 2500.
Curator
mj_li