Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension‐induced heart failure

Abstract

AimsRecent studies have shown that microRNAs (miRNAs), besides being potent regulators of gene expression, can additionally serve as circulating biomarkers of disease. The aim of this study is to determine if plasma miRNAs can be used as indicators of disease progression or therapeutic efficacy in hypertension-induced heart disease. Methods and resultsIn order to define circulating miRNAs that change during hypertension-induced heart failure and that respond to therapeutic treatment, we performed miRNA arrays on plasma RNA from hypertensive rats that show signs of heart failure. Array analysis indicated that approximately one-third of the miRNAs on the array are detectable in plasma. Quantitative real-time polymerase chain reaction (PCR) analysis for a selected panel of miRNAs indicated that circulating levels of miR-16, miR-20b, miR-93, miR-106b, miR-223, and miR-423-5p were significantly increased in response to hypertension-induced heart failure, while this effect was blunted in response to treatment with antimiR-208a as well as an ACE inhibitor. Moreover, treatment with antimiR-208a resulted in a dramatic increase in one miRNA, miR-19b. A time course study indicated that several of these miRNA changes track with disease progression. ConclusionsCirculating levels of miRNAs are responsive to therapeutic interventions and change during the progression of hypertension-induced heart disease.--

Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers

“…Increases in circulating miRNAs upon cell damage have been detected by RT-PCR-based approaches for liver, brain, and skeletal muscle (5), as well as heart (19,46 instances miRNAs even performed better than established protein biomarkers (5). Our analysis indicated that heart-specific myomirs performed similar to the highly sensitive cTnI assay, but we were unable to verify the utility of any recently proposed miRNA biomarker for HF (18,(20)(21)(22). Considering that sRNAseq experiments capture a wide spectrum of miRNAs as well as fragments of other classes of RNAs, and can be performed with low ng quantities of total RNA recoverable from 250 μL plasma or serum, this approach holds great potential for future RNA biomarker discovery.…”

“…S1) were shown to contribute to muscle or myocardial function (8, 9). miRNAs and other classes of RNA have been profiled in failing human myocardium (10)(11)(12)(13)(14)(15)(16)(17), and a selected subset was also investigated as circulating biomarkers in HF (18)(19)(20)(21)(22)(23)(24). However, in these studies heart tissue and circulating miRNA abundance changes were not acquired simultaneously to correlate changes in tissue versus circulating miRNA composition.…”

Circulating microRNAs and hypertension—from new insights into blood pressure regulation to biomarkers of cardiovascular risk

“…[24] Interestingly, it was also noted that these microRNAs increased during disease progression and were reduced in response to treatment with ACE inhibitor. [24] Whilst the limitations of an animal model must be accepted, this work highlights great potential for microRNAs to not only act as biomarkers of target-organ damage, but also of disease progression and response to treatment.…”

“…[24] Interestingly, it was also noted that these microRNAs increased during disease progression and were reduced in response to treatment with ACE inhibitor. [24] Whilst the limitations of an animal model must be accepted, this work highlights great potential for microRNAs to not only act as biomarkers of target-organ damage, but also of disease progression and response to treatment. More recently, Sanchez-de-la-Torre et al screened 84 'cardiovascular' microRNAs to identify a panel of three plasma microRNAs whose pre-treatment levels could accurately predict blood pressure lowering response to continuous positive airway pressure (CPAP) in patients with resistant hypertension and obstructive sleep apnoea.…”

The relationship between circulating microRNAs and left ventricular mass in symptomatic heart failure patients with systolic dysfunction

“…In recent years, numerous studies have addressed the association between dysregulated miRNAs and LV hypertrophy in the context of HF in animals and humans. In a study carried out on a hypertension-induced HF mouse model using polymerase chain reaction analysis for a selected panel of miRNAs it was demonstrated that circulating levels of miR-16, miR-20b, miR-93, miR-106b, miR-223, and miR-423-5p were significantly increased in response to hypertension-induced HF, while this effect was blunted in response to treatment with antimiR-208a as well as an angiotensin-converting enzyme inhibitor [11]. Endo et al [1] demonstrated through miRNA array analysis that miRNA-15a and b, miR-20a, miR-103, miR-130a and b, miR-195, miR-210, miR-301b, miR-451, and miR-494 were dysregulated in rats with HF.…”