“…FC: fold change. Myocardial injury/infarction Heart failure Atherosclerosis miRNA FC P value miRNA FC P value miRNA FC P value miR-298 30 2.1 1.2 × 10 –7 miR-148a 37 1.23 7.6 × 10 –4 miR-130a 27 1.66 1.9 × 10 –29 miR-135a 33 , 34 − 1.63 2.7 × 10 –4 let-7i 35 , 36 1.16 3.7 × 10 –5 miR-204 28 − 1.22 1.4 × 10 –8 miR-31 32 1.5 6.4 × 10 –10 miR-30b 31 1.2 3.8 × 10 –6 Figure 3 Analysis of candidate miRNAs in the heart by qPCR. Relative miRNA expression was measured in wild-type (wt; n = 7), AGAT knockout (AGAT -/- ; n = 7), homoarginine-supplemented AGAT -/- (AGAT -/- hArg; n = 5) and creatine-supplemented AGAT -/- (AGAT -/- Cr; n = 4) mice.…”
Section: Resultsmentioning
confidence: 99%
“…Regarding creatine, the expression of miR-30b, miR-31, miR-130a, miR-148a, and miR-204 showed regulation towards wt levels by creatine supplementation in AGAT -/- mice. MiR-30b and miR-31 were both upregulated in AGAT -/- mice and found to be involved in regulating cardiomyocyte apoptosis and remodeling after myocardial injury 31 , 32 . MiR-148a which was highly expressed in LV tissue and showed upregulation in AGAT -/- animals has been described to be involved in HF 37 , while miR-130a and miR-204 play a role in atherosclerosis.…”
In humans and mice, L-arginine:glycine amidinotransferase (AGAT) and its metabolites homoarginine (hArg) and creatine have been linked to cardiovascular disease (CVD), specifically myocardial infarction (MI) and heart failure (HF). The underlying molecular and regulatory mechanisms, however, remain unclear. To identify potential pathways of cardiac AGAT metabolism, we sequenced microRNA (miRNA) in left ventricles of wild-type (wt) compared to AGAT-deficient (AGAT-/-) mice. Using literature search and validation by qPCR, we identified eight significantly regulated miRNAs in AGAT-/- mice linked to atherosclerosis, MI and HF: miR-30b, miR-31, miR-130a, miR-135a, miR-148a, miR-204, miR-298, and let-7i. Analysis of Gene Expression Omnibus (GEO) data confirmed deregulation of these miRNAs in mouse models of MI and HF. Quantification of miRNA expression by qPCR in AGAT-/- mice supplemented with creatine or hArg revealed that miR-30b, miR-31, miR-130a, miR-148a, and miR-204 were regulated by creatine, while miR-135a and miR-298 showed a trend of regulation by hArg. Finally, bioinformatics-based target prediction showed that numerous AGAT-dependent genes previously linked to CVD are likely to be regulated by the identified miRNAs. Taken together, AGAT deficiency and hArg/creatine supplementation are associated with cardiac miRNA expression which may influence cardiac (dys)function and CVD.
“…FC: fold change. Myocardial injury/infarction Heart failure Atherosclerosis miRNA FC P value miRNA FC P value miRNA FC P value miR-298 30 2.1 1.2 × 10 –7 miR-148a 37 1.23 7.6 × 10 –4 miR-130a 27 1.66 1.9 × 10 –29 miR-135a 33 , 34 − 1.63 2.7 × 10 –4 let-7i 35 , 36 1.16 3.7 × 10 –5 miR-204 28 − 1.22 1.4 × 10 –8 miR-31 32 1.5 6.4 × 10 –10 miR-30b 31 1.2 3.8 × 10 –6 Figure 3 Analysis of candidate miRNAs in the heart by qPCR. Relative miRNA expression was measured in wild-type (wt; n = 7), AGAT knockout (AGAT -/- ; n = 7), homoarginine-supplemented AGAT -/- (AGAT -/- hArg; n = 5) and creatine-supplemented AGAT -/- (AGAT -/- Cr; n = 4) mice.…”
Section: Resultsmentioning
confidence: 99%
“…Regarding creatine, the expression of miR-30b, miR-31, miR-130a, miR-148a, and miR-204 showed regulation towards wt levels by creatine supplementation in AGAT -/- mice. MiR-30b and miR-31 were both upregulated in AGAT -/- mice and found to be involved in regulating cardiomyocyte apoptosis and remodeling after myocardial injury 31 , 32 . MiR-148a which was highly expressed in LV tissue and showed upregulation in AGAT -/- animals has been described to be involved in HF 37 , while miR-130a and miR-204 play a role in atherosclerosis.…”
In humans and mice, L-arginine:glycine amidinotransferase (AGAT) and its metabolites homoarginine (hArg) and creatine have been linked to cardiovascular disease (CVD), specifically myocardial infarction (MI) and heart failure (HF). The underlying molecular and regulatory mechanisms, however, remain unclear. To identify potential pathways of cardiac AGAT metabolism, we sequenced microRNA (miRNA) in left ventricles of wild-type (wt) compared to AGAT-deficient (AGAT-/-) mice. Using literature search and validation by qPCR, we identified eight significantly regulated miRNAs in AGAT-/- mice linked to atherosclerosis, MI and HF: miR-30b, miR-31, miR-130a, miR-135a, miR-148a, miR-204, miR-298, and let-7i. Analysis of Gene Expression Omnibus (GEO) data confirmed deregulation of these miRNAs in mouse models of MI and HF. Quantification of miRNA expression by qPCR in AGAT-/- mice supplemented with creatine or hArg revealed that miR-30b, miR-31, miR-130a, miR-148a, and miR-204 were regulated by creatine, while miR-135a and miR-298 showed a trend of regulation by hArg. Finally, bioinformatics-based target prediction showed that numerous AGAT-dependent genes previously linked to CVD are likely to be regulated by the identified miRNAs. Taken together, AGAT deficiency and hArg/creatine supplementation are associated with cardiac miRNA expression which may influence cardiac (dys)function and CVD.
“…Some miRNAs protect cardiomyocytes from apoptosis following acute MI through activation of Wnt/β-catenin and PI3K/AKT pathways and their downstream regulators. MiR-30b-5p participates in myocardial cell proliferation and apoptosis by modulation of the Wnt/β-catenin signalling pathway, possibly providing the new underlying target to diagnose MI in the clinic (Chi et al, 2020). MiR-34a affects myocardial cell apoptosis by regulating the activation and inactivation of the Wnt/β-catenin signalling pathway (Li JH.…”
Section: Mirnas In Cardiomyocyte Apoptosismentioning
confidence: 99%
“…The present study addresses the regulatory role and functions of circRNAs, discusses the latest studies, and investigates the role and the regulatory mechanism of circRNAs in MI. Moreover, the roles of circRNAs in multiple MI such as myocardial apoptosis (Wang K. et al, 2017;Cai et al, 2019;Chai et al, 2020;Liu X. et al, 2020, 29;Zhai et al, 2020;Chen T.-P. et al, 2021;Wu Y. et al, 2021;Zhang J. et al, 2021;Zhao B. et al, 2021;, autophagy regulation, inflammatory response (Hu et al, 2020;Zhu Y. et al, 2020;Bian et al, 2021;Cai et al, 2021, 3), improvement of fibrosis (Zhu et al, 2019;Li F. et al, 2020;Sun L.y. et al, 2020;Si et al, 2020), and effects of ventricular remodelling (Garikipati et al, 2019;Cheng et al, 2020) (Gao et al, 2020;Tan et al, 2021, 4;Zhao Q. et al, 2021) have been summarised (Figure 3).…”
Myocardial infarction (MI) is a complicated pathology triggered by numerous environmental and genetic factors. Understanding the effect of epigenetic regulation mechanisms on the cardiovascular disease would advance the field and promote prophylactic methods targeting epigenetic mechanisms. Genetic screening guides individualised MI therapies and surveillance. The present review reported the latest development on the epigenetic regulation of MI in terms of DNA methylation, histone modifications, and microRNA-dependent MI mechanisms and the novel therapies based on epigenetics.
“…[ 9–11 ]. Moreover, miR-30b-5p can promote the apoptosis of cardiomyocytes in rats with myocardial infarction via modulating the Wnt/β-catenin signal pathway [ 12 ]. MiR-30b-5p is up-regulated in AC16 cells under hypoxia; miR-30b-5p inhibition can alleviate hypoxia-induced injury of cardiomyocyte via targeting Aven [ 13 ].…”
Dysfunction of airway smooth muscle (ASM) cells is crucial in asthma pathogenesis. Here, microRNA-30b-5p (miR-30b-5p)’s function and mechanism in ASM cells’ multiplication and migration were investigated. Microarray was utilized for identifying the differentially expressed miRNAs in the bronchial epithelial cells of the asthma patients and healthy controls. Platelet-derived growth factor (PDGF) was employed to treat ASM cells to establish an
in-vitro
asthma model. Quantitative real-time PCR (qRT-PCR) was conducted for detecting the expressions of miR-30b-5p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2ʹ-deoxyuridine (BrdU) assays were used for examining cell multiplication; Transwell assay was performed for detecting cell migration; cell cycle was analyzed through flow cytometry. The targeted relationship between PTEN and miR-30b-5p was verified using a dual-luciferase reporter gene assay. Western blot was used for detecting the expressions of phosphorylated (p)-phosphatidylinositol 3-kinase (PI3K), PTEN, PI3K, protein kinase B (AKT) and p-AKT in ASM cells. We demonstrated that, miR-30b-5p expression in the bronchial epithelial cells of asthmatic patients was up-regulated. It was also increased in PDGF-stimulated ASM cells. Transfection of miR-30b-5p mimics facilitated ASM cells’ multiplication, migration and cycle progression, while inhibiting miR-30b-5p had the opposite effect. Furthermore, miR-30b-5p could target PTEN to repress PTEN expression. PTEN overexpression attenuated the effect of miR-30b-5p on ASM cells. Moreover, miR-30b-5p overexpression facilitated the expression of p-PI3K and p-AKT in PDGF-stimulated ASM cells. Collectively, miR-30b-5p activates the PI3K/AKT pathway by targeting PTEN to facilitate PDGF-induced dysfunction of ASM cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
