An Analysis of the Global Expression of MicroRNAs in an Experimental Model of Physiological Left Ventricular Hypertrophy

Abstract

BackgroundMicroRNAs (miRs) are a class of small non-coding RNAs that regulate gene expression. Studies of transgenic mouse models have indicated that deregulation of a single miR can induce pathological cardiac hypertrophy and cardiac failure. The roles of miRs in the genesis of physiological left ventricular hypertrophy (LVH), however, are not well understood.ObjectiveTo evaluate the global miR expression in an experimental model of exercise-induced LVH.MethodsMale Balb/c mice were divided into sedentary (SED) and exercise (EXE) groups. Voluntary exercise was performed on an odometer-monitored metal wheels for 35 days. Various tests were performed after 7 and 35 days of training, including a transthoracic echocardiography, a maximal exercise test, a miR microarray (miRBase v.16) and qRT-PCR analysis.ResultsThe ratio between the left ventricular weight and body weight was increased by 7% in the EXE group at day 7 (p<0.01) and by 11% at day 35 of training (p<0.001). After 7 days of training, the microarray identified 35 miRs that were differentially expressed between the two groups: 20 were up-regulated and 15 were down-regulated in the EXE group compared with the SED group (p = 0.01). At day 35 of training, 25 miRs were differentially expressed: 15 were up-regulated and 10 were decreased in the EXE animals compared with the SED animals (p<0.01). The qRT-PCR analysis demonstrated an increase in miR-150 levels after 35 days and a decrease in miR-26b, miR-27a and miR-143 after 7 days of voluntary exercise.ConclusionsWe have identified new miRs that can modulate physiological cardiac hypertrophy, particularly miR-26b, -150, -27a and -143. Our data also indicate that previously established regulatory gene pathways involved in pathological LVH are not changed in physiological LVH.

Plasma levels of microRNA in chronic kidney disease: patterns in acute and chronic exercise

“…Recently, miR-150 was also found to be a modulator of physiological cardiac hypertrophy in response to exercise (21). Whether increase of plasma miR-150 levels relates to cardiovascular exercise-induced adaptation, i.e., left ventricular hypertrophy or the increased mobilization of EPCs, remains to be experimentally validated in an in vivo animal model of physical exercise.…”

Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy

“…miR-1, miR-133, miR199a/b, miR-21, miR-23, miR-26, miR-29, miR-9, miR-98, and miR-499) have been shown to exert either a positive or negative influence on pathological cardiac hypertrophy (4 -6). Whereas several studies have recently profiled microRNA expression signatures in rat physiological hypertrophic hearts induced by swimming or treadmill training, it still remains unknown how dys-regulated miRNAs contribute to physiological hypertrophy (7)(8)(9)(10).…”

The Role of MicroRNAs in the Cardiac Response to Exercise

“…In exercised rats, miR-27a and -27b were reported to increase while miR-143 decreased, together with reciprocal changes in expression of their angiotensin-converting enzyme targets, ACE and ACE2, respectively, suggesting specific miRNAs targeting renin -angiotensin system genes are dynamically modulated by exercise training and may contribute, at least in part, to the progression of cardiac hypertrophy . Using a microarray to assess .1000 murine miRNAs in exercise-induced LV hypertrophy, Martinelli et al (2014) identified 35 miRNAs differentially expressed after 1 week of exercise relative to sedentary controls and 25 miRNAs differentially expressed after 5 weeks of training, documenting temporal regulation of cardiac miRNAs during exercise training. We profiled miRNAs in hearts of mice subjected to 3 weeks of either an intense swimming protocol or voluntary wheel running.…”

“…In contrast, fewer studies have directly examined the functional role of miRNAs in physiological cardiac hypertrophy Soci et al 2011;Liu et al 2015). However, multiple studies have identified cardiac miRNAs differentially regulated in exercise, which were known to regulate pathological hypertrophy, including miRNAs in Table 1 (Care et al 2007;Fernandes et al 2011;Soci et al 2011;Ma et al 2013;Martinelli et al 2014;Liu et al 2015). Thus, although the functional contributions of most have not been directly assessed in exercise-induced hypertrophy, these miRNAs may also modulate physiological hypertrophy.…”

“…Many of the miRNAs identified as altered in exercised hearts have documented roles regulating apoptosis or necroptosis, and therefore could provide mechanistic links between exercise and cardioprotection (Fig. 2B) Dong et al 2009;Lin et al 2010;Wang et al 2011;Ma et al 2013;Martinelli et al 2014;Liu et al 2015;Ramasamy et al 2015;Zhao 2015;Qin et al 2016). However, functional effects in cardiomyocytes in vitro or in vivo have only been investigated in a minority of cases and only rarely has cardioprotection against ischemic injury been investigated.…”