Deregulated hepatic micro<scp>RNA</scp>s underlie the association between non‐alcoholic fatty liver disease and coronary artery disease

Braza-Boïls, Aitana; Marí-Alexandre, Josep; Molina, Pilar; Arnau, Miguel Á.; Barceló-Molina, Moisés; Domingo, Diana; Girbés, Javier; Giner, Juan Manuel Llopis; Martínez‐Dolz, Luis; Zorio, Esther

doi:10.1111/liv.13097

Cited by 38 publications

(41 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, only miR-34a was up-regulated in NAFLD compared with CHB patients, indicating that miR-34a may be a more sensitive indicator of NAFLD than CHB. Increased miR-34a levels have been reported in the serum and liver of NAFLD patients and animal models[15,16,21], and our results suggested that miR-34a could distinguish NAFLD not only from healthy controls but also from other liver diseases, such as CHB.…”

Section: Discussionsupporting

confidence: 68%

Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population

Liu¹,

Pan²,

Zhang³

et al. 2016

WJG

View full text Add to dashboard Cite

AIMTo assess disease-specific circulating microRNAs (miRNAs) in non-alcoholic steatohepatitis (NASH) patients.METHODSA total of 111 biopsy-proven non-alcoholic fatty liver disease (NAFLD) or chronic hepatitis B (CHB) patients and healthy controls from mainland China were enrolled to measure their serum levels of miR-122, -125b, -146b, -16, -21, -192, -27b and -34a. The correlations between serum miRNAs and histological features of NAFLD were determined. The diagnostic value of miRNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI), respectively.RESULTSCirculating miR-122, -16, -192 and -34a showed differential expression levels between NAFLD and CHB patients, and miR-34a had an approximately 2-fold increase in NAFLD samples compared with that of CHB samples (P < 0.01). Serum miR-122, -192 and -34a levels were correlated with steatosis (R = 0.302, 0.323 and 0.470, respectively, P < 0.05) and inflammatory activity (R = 0.445, 0.447 and 0.517, respectively, P < 0.01); only serum miR-16 levels were associated with fibrosis (R = 0.350, P < 0.05) in patients with NAFLD. The diagnostic value of miR-34a for NASH (area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but miR-16 showed a limited performance in the diagnosis of significant fibrosis in NASH.CONCLUSIONCirculating miR-34a may serve as a disease-specific noninvasive biomarker for the diagnosis of NASH.

show abstract

Section: Discussionsupporting

confidence: 68%

Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population

Liu¹,

Pan²,

Zhang³

et al. 2016

WJG

View full text Add to dashboard Cite

show abstract

“…Although recent advances in early detection and therapies have been developed, CHD is still the major cause of sudden cardiac death and hospitalization around the world [2, 3]. According to statistics from 2012, 4.5% Asians over 18-years-old suffer from CHD, and the prevalence of this disease would increase by roughly 18% by 2030 [4].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Huang

Wei

Lin

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: This study aimed to identify the role of microRNA-22 (miR-22) in endothelial cell (EC) injury in coronary heart disease (CHD) by targeting NLRP3 through the inflammasome signaling pathway. Methods: A total of 24 healthy male Sprague-Dawley (SD) rats were divided into normal and atherosclerosis groups. The atherosclerosis rats were assigned into blank, negative control (NC), miR-22 mimic, miR-22 inhibitor and miR-22 inhibitor + siNLRP3 groups. A luciferase reporter gene assay was used to detect the relationship between miR-22 and NLRP3. MiR-22 expression as well as NLRP3 and caspase-1 mRNA and protein expression were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The activity and apoptosis of coronary arterial endothelial cells (CAECs) were determined by MTT and Hoechst 33258. CAEC lumen formation was detected by a lumen formation assay. An enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β, IL-6, IL-10 and IL-18 levels. Results: The results indicated that the atherosclerosis group significantly decreased miR-22 expression but increased NLRP3 and caspase-1 mRNA and protein expression. The cell survival rate was significantly increased in the miR-22 mimic group and significantly reduced in the miR-22 inhibitor group. The miR-22 mimic group displayed a lower apoptosis rate and more cells with obvious lumen walls and numerous tubular structures, while cells in the miR-22 inhibitor group were unable to form lumen walls and had a scattered distribution compared to the blank group. The ELISA showed that IL-1β, IL-6 and IL-18 levels were markedly decreased, while IL-10 was clearly increased in the miR-22 mimic group. In contrast, in the miR-22 inhibitor group, IL-1β, IL-6 and IL-18 levels were significantly increased, and IL-10 levels were decreased. Conclusion: Our findings indicated that miR-22 could lower the levels of pro-inflammatory cytokines by inhibiting the NLRP3 inflammasome pathway, which suppresses CAEC apoptosis and protects CAECs in rats with CHD.

show abstract

“…However, in pathologic conditions such as NAFLD, miR-29 seemed not to be induced in the liver. A decrease of miR-29c was observed in patients with NASH versus controls [50] , although the miR-29a and miR-29b levels in NAFLD need to be studied in the future. In addition, miR-29c was downregulated in NASH animal livers of C57BL/6J and DBA/2J mice fed with methyl-deficient diet, with respect to the control group [51] .…”

Section: Discussionmentioning

confidence: 99%

Dicer1/miR-29/HMGCR axis contributes to hepatic free cholesterol accumulation in mouse non-alcoholic steatohepatitis

et al. 2017

View full text Add to dashboard Cite

Dicer1 is an enzyme essential for microRNA (miRNA) maturation. The loss of miRNAs resulted from Dicer1 deficiency greatly contributes to the progression of many diseases, including lipid dysregulation, but its role in hepatic accumulation of free cholesterol (FC) that is critical in the development of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we used the liver-specific Dicer1-knockout mice to identify the miRNAs involved in hepatic FC accumulation. In a widely used dietary NASH model, mice were fed a methionine-choline-deficient (MCD) diet for 3 weeks, which resulted in significant increase in hepatic FC levels as well as decrease of Dicer1 mRNA levels in livers. The liver-specific Dicer1-knockout induced hepatic FC accumulation at 5-6 weeks, accompanied by increased mRNA and protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme of cholesterol synthesis in livers. Eleven predicted miRNAs were screened, revealing that miR-29a/b/c significantly suppressed HMGCR expression by targeting the HMGCR mRNA 3'-UTR. Overexpression of miR-29a in SMMC-7721 cells, a steatosis hepatic cell model, significantly decreased HMGCR expression and the FC level. Furthermore, the expression levels of miR-29a were inversely correlated with HMGCR expression levels in the MCD diet mouse model in vivo and in 2 steatosis hepatic cell models (SMMC-7721 and HL-7702 cells) in vitro. Our results show that Dicer1/miR-29/HMGCR axis contributes to hepatic free cholesterol accumulation in mouse NASH, and miR-29 may serve as an important regulator of hepatic cholesterol homeostasis. Thus, miR-29a could be utilized as a potential therapeutic target for the treatment of non-alcoholic fatty liver disease as well as for other liver diseases associated with FC accumulation.

show abstract

Deregulated hepatic microRNAs underlie the association between non‐alcoholic fatty liver disease and coronary artery disease

Abstract: CAD is associated with NAFLD and NASH. The hepatic miRNAs studied appear to be associated with NAFLD severity and may promote CAD through lipid metabolism alteration and/or promotion of the systemic inflammation.

Cited by 38 publications

References 45 publications

Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population

Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Dicer1/miR-29/HMGCR axis contributes to hepatic free cholesterol accumulation in mouse non-alcoholic steatohepatitis

Contact Info

Product

Resources

About