Sensory Neuropathy Affects Cardiac miRNA Expression Network Targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2 mRNAs

Abstract

Background: Here we examined myocardial microRNA (miRNA) expression profile in a sensory neuropathy model with cardiac diastolic dysfunction and aimed to identify key mRNA molecular targets of the differentially expressed miRNAs that may contribute to cardiac dysfunction. Methods: Male Wistar rats were treated with vehicle or capsaicin for 3 days to induce systemic sensory neuropathy. Seven days later, diastolic dysfunction was detected by echocardiography, and miRNAs were isolated from the whole ventricles. Results: Out of 711 known miRNAs measured by miRNA microarray, the expression of 257 miRNAs was detected in the heart. As compared to vehicle-treated hearts, miR-344b, miR-466b, miR-98, let-7a, miR-1, miR-206, and miR-34b were downregulated, while miR-181a was upregulated as validated also by quantitative real time polymerase chain reaction (qRT-PCR). By an in silico network analysis, we identified common mRNA targets (insulin-like growth factor 1 (IGF-1), solute carrier family 2 facilitated glucose transporter member 12 (SLC2a-12), eukaryotic translation initiation factor 4e (EIF-4e), and Unc-51 like autophagy activating kinase 2 (ULK-2)) targeted by at least three altered miRNAs. Predicted upregulation of these mRNA targets were validated by qRT-PCR. Conclusion: This is the first demonstration that sensory neuropathy affects cardiac miRNA expression network targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2, which may contribute to cardiac diastolic dysfunction. These results further support the need for unbiased omics approach followed by in silico prediction and validation of molecular targets to reveal novel pathomechanisms.

Modulation of Sensory Nerve Function by Insulin: Possible Relevance to Pain, Inflammation and Axon Growth

“…It has also been shown that long-term application of insulin modifies the expression of the TRPV1 receptor protein in neuroblastoma cells by regulating the PI3K and MAPK signaling [21]. Additionally, in a recent publication it has been demonstrated, that selective chemodenervation evoked by neonatal capsaicin treatment resulted in changes in myocardial miRNA expression targeting among others the expression network of IGF-1 [81].…”

Analysis of the differential expression profile of miRNAs in myocardial tissues of rats with burn injury

“…A downstream target of miR-344b is Olig2 [40]. The cardiac expression of miR-344b is affected by sensory neuropathy, but the mechanism is unclear [41]. In our study, we first identified the aberrantly high expression of miR-344b in burn injury-induced cardiac dysfunction.…”

Capsaicin-Sensitive Sensory Nerves and the TRPV1 Ion Channel in Cardiac Physiology and Pathologies

“…Recently, we have found an increased end-diastolic diameter, and reduced stroke volume, but maintained EF and FS, after systemic capsaicin-induced sensory desensitization in rats [ 103 ]. Disturbed relaxation was due to reduced basal cardiac NO, superoxide, and peroxynitrite (ONOO − ) formation, and thereby impairment of the physiological S-nitrosylation level of the sarco-endoplasmic reticulum Ca 2+ ATPase 2a (SERCA2a) [ 104 ]. Moreover, we have also investigated the effects of systemic capsaicin-induced sensory neuropathy on cardiac miRNA transcriptomics and shown an altered miRNA expression pattern.…”