Limits...
Effects of miRNA-455 on cardiac hypertrophy induced by pressure overload.

Wu C, Dong S, Li Y - Int. J. Mol. Med. (2015)

Bottom Line: The mice were randomly selected to receive a tail vein injection of either miR-455 or green fluorescent protein per animal at 1, 8, 15 and 21 days following surgery.TAC (2 weeks following surgery) resulted in significant cardiac hypertrophy, which was significantly aggravated by treatment with miR-455.However, miR-455 replacement therapy markedly reduced myocardial fibrosis and inhibited apoptosis, suggesting that this therapy can prevent maladaptive ventricular remodeling. miR-455 was also identified and validated to target calreticulin, a protein that is critical for cardiac development.

View Article: PubMed Central - PubMed

Affiliation: Intensive Care Unit, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China.

ABSTRACT
microRNAs (miRNAs or miRs) are essential in cardiac hypertrophy and in the development of heart failure. In the present study, we aimed to determine whether the restoration of miRNA-455 (miR-455) gene expression in vivo aggravates hypertrophy, but protects against adverse cardiac remodeling induced by pressure overload. Cardiac hypertrophy was induced by left ventricular pressure overload in male mice subjected to transverse aortic constriction (TAC). The mice were randomly selected to receive a tail vein injection of either miR-455 or green fluorescent protein per animal at 1, 8, 15 and 21 days following surgery. Cardiac hypertrophy, function and remodeling were evaluated by echocardiography, catheterization, histological analysis and the examination of the expression of specific genes and cardiac apoptosis. TAC (2 weeks following surgery) resulted in significant cardiac hypertrophy, which was significantly aggravated by treatment with miR-455. However, miR-455 replacement therapy markedly reduced myocardial fibrosis and inhibited apoptosis, suggesting that this therapy can prevent maladaptive ventricular remodeling. miR-455 was also identified and validated to target calreticulin, a protein that is critical for cardiac development. The restoration of miR-455 gene expression may thus be a potential therapeutic strategy to reverse pressure-induced cardiac hypertrophy and prevent maladaptive cardiac remodeling through the regulation of miR-455 at different time points following hypertrophy.

Show MeSH

Related in: MedlinePlus

Bioinformatics analysis identified Calr as a putative target gene of miR-455. Calr, calreticulin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4356433&req=5

f1-ijmm-35-04-0893: Bioinformatics analysis identified Calr as a putative target gene of miR-455. Calr, calreticulin.

Mentions: Cardiac hypertrophy is a pathological characteristic common to numerous forms of heart disease, such as hypertension, ischemic myocardial injury, diabetic cardiomyopathy, valvular dysfunction and aortic stenosis (1). Persistent hypertrophy can ultimately lead to ventricular dilatation, arrhythmia, fibrotic disease, heart failure and even sudden death (2,3). Cardiac hypertrophy is a major risk factor in the development of heart failure, and its therapeutic reversal is associated with decreased mortality (4,5). Previous studies have indicated that microRNAs (miRNAs or miRs) are essential in a number of biological processes, including differentiation, apoptosis, proliferation and development (6,7). The dysregulation of miRNAs has been linked to several human diseases (7), including cardiovascular disease (8,9). miRNAs are a class of highly conserved, small non-coding RNAs (approximately 23 nucleotides in length) that regulate gene expression at the post-transcriptional level (10). miRNAs inhibit gene expression by forming partial duplexes with the 3′-untranslated region (3′-UTR) of mRNAs (11,12). miRNAs function by either inhibiting mRNA translation or promoting mRNA degradation (13). Each miRNA can have numerous mRNA targets (14). In addition, a single mRNA can be targeted by different miRNAs, thereby increasing the complexity of gene regulation by miRNAs. miRNAs have been found in various organisms and are regarded as powerful regulators of gene expression and cellular phenotype. Moreover, their roles in cardiovascular biology and diseases have been an area of intense investigation. Previous studies have identified the expression patterns of miRNAs associated with cardiovascular diseases. For example, miRNA-21, miRNA-23a, miRNA-24, miRNA-133, miRNA-208/miRNA-195 and miRNA-199 have been shown to be involved in cardiac hypertrophy (15-17), miRNA-1 in arrhythmia (18), miRNA-29 and miRNA-21 in cardiac fibrosis (19,20), miRNA-210 and miRNA-494 in ischemic heart disease (21) and miRNA-129 in heart failure (22). However, the association between miRNA-455 (miR-455) and cardiac hypertrophy remains unclear. In this study, using a target prediction algorithm (23), we identified calreticulin (Calr) as the putative target gene of miR-455. The mRNA sequence of Calr was predicted to contain a conserved ‘seed’ sequence complementary to miR-455 in the 3′-UTR (Fig. 1). Calr is closely associated with myocardial hypertrophy (24). Thus, miR-455 may be important in myocardial hypertrophy. In the present study, we established a mouse model of hypertrophy by transverse aortic constriction (TAC) in order to investigate the effects of the aberrant expression of miR-455 on cardiac hypertrophy induced by pressure overload and to elucidate the potential cellular and molecular mechanisms of action of this miRNA.


Effects of miRNA-455 on cardiac hypertrophy induced by pressure overload.

Wu C, Dong S, Li Y - Int. J. Mol. Med. (2015)

Bioinformatics analysis identified Calr as a putative target gene of miR-455. Calr, calreticulin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356433&req=5

f1-ijmm-35-04-0893: Bioinformatics analysis identified Calr as a putative target gene of miR-455. Calr, calreticulin.
Mentions: Cardiac hypertrophy is a pathological characteristic common to numerous forms of heart disease, such as hypertension, ischemic myocardial injury, diabetic cardiomyopathy, valvular dysfunction and aortic stenosis (1). Persistent hypertrophy can ultimately lead to ventricular dilatation, arrhythmia, fibrotic disease, heart failure and even sudden death (2,3). Cardiac hypertrophy is a major risk factor in the development of heart failure, and its therapeutic reversal is associated with decreased mortality (4,5). Previous studies have indicated that microRNAs (miRNAs or miRs) are essential in a number of biological processes, including differentiation, apoptosis, proliferation and development (6,7). The dysregulation of miRNAs has been linked to several human diseases (7), including cardiovascular disease (8,9). miRNAs are a class of highly conserved, small non-coding RNAs (approximately 23 nucleotides in length) that regulate gene expression at the post-transcriptional level (10). miRNAs inhibit gene expression by forming partial duplexes with the 3′-untranslated region (3′-UTR) of mRNAs (11,12). miRNAs function by either inhibiting mRNA translation or promoting mRNA degradation (13). Each miRNA can have numerous mRNA targets (14). In addition, a single mRNA can be targeted by different miRNAs, thereby increasing the complexity of gene regulation by miRNAs. miRNAs have been found in various organisms and are regarded as powerful regulators of gene expression and cellular phenotype. Moreover, their roles in cardiovascular biology and diseases have been an area of intense investigation. Previous studies have identified the expression patterns of miRNAs associated with cardiovascular diseases. For example, miRNA-21, miRNA-23a, miRNA-24, miRNA-133, miRNA-208/miRNA-195 and miRNA-199 have been shown to be involved in cardiac hypertrophy (15-17), miRNA-1 in arrhythmia (18), miRNA-29 and miRNA-21 in cardiac fibrosis (19,20), miRNA-210 and miRNA-494 in ischemic heart disease (21) and miRNA-129 in heart failure (22). However, the association between miRNA-455 (miR-455) and cardiac hypertrophy remains unclear. In this study, using a target prediction algorithm (23), we identified calreticulin (Calr) as the putative target gene of miR-455. The mRNA sequence of Calr was predicted to contain a conserved ‘seed’ sequence complementary to miR-455 in the 3′-UTR (Fig. 1). Calr is closely associated with myocardial hypertrophy (24). Thus, miR-455 may be important in myocardial hypertrophy. In the present study, we established a mouse model of hypertrophy by transverse aortic constriction (TAC) in order to investigate the effects of the aberrant expression of miR-455 on cardiac hypertrophy induced by pressure overload and to elucidate the potential cellular and molecular mechanisms of action of this miRNA.

Bottom Line: The mice were randomly selected to receive a tail vein injection of either miR-455 or green fluorescent protein per animal at 1, 8, 15 and 21 days following surgery.TAC (2 weeks following surgery) resulted in significant cardiac hypertrophy, which was significantly aggravated by treatment with miR-455.However, miR-455 replacement therapy markedly reduced myocardial fibrosis and inhibited apoptosis, suggesting that this therapy can prevent maladaptive ventricular remodeling. miR-455 was also identified and validated to target calreticulin, a protein that is critical for cardiac development.

View Article: PubMed Central - PubMed

Affiliation: Intensive Care Unit, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China.

ABSTRACT
microRNAs (miRNAs or miRs) are essential in cardiac hypertrophy and in the development of heart failure. In the present study, we aimed to determine whether the restoration of miRNA-455 (miR-455) gene expression in vivo aggravates hypertrophy, but protects against adverse cardiac remodeling induced by pressure overload. Cardiac hypertrophy was induced by left ventricular pressure overload in male mice subjected to transverse aortic constriction (TAC). The mice were randomly selected to receive a tail vein injection of either miR-455 or green fluorescent protein per animal at 1, 8, 15 and 21 days following surgery. Cardiac hypertrophy, function and remodeling were evaluated by echocardiography, catheterization, histological analysis and the examination of the expression of specific genes and cardiac apoptosis. TAC (2 weeks following surgery) resulted in significant cardiac hypertrophy, which was significantly aggravated by treatment with miR-455. However, miR-455 replacement therapy markedly reduced myocardial fibrosis and inhibited apoptosis, suggesting that this therapy can prevent maladaptive ventricular remodeling. miR-455 was also identified and validated to target calreticulin, a protein that is critical for cardiac development. The restoration of miR-455 gene expression may thus be a potential therapeutic strategy to reverse pressure-induced cardiac hypertrophy and prevent maladaptive cardiac remodeling through the regulation of miR-455 at different time points following hypertrophy.

Show MeSH
Related in: MedlinePlus