Existence of a Strong Correlation of Biomarkers and miRNA in Females with Metabolic Syndrome and Obesity in a Population of West Virginia

Goguet-Rubio, Perrine; Klug, Rebecca L.; Sharma, Dana; Srikanthan, Krithika; Puri, Nitin; Lakhani, Vishal; Nichols, Alexandra; O’Hanlon, Kathleen; Abraham, Nader G.; Shapiro, Joseph I.; Sodhi, Komal

doi:10.7150/ijms.18988

Cited by 28 publications

(25 citation statements)

References 42 publications

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“…Three technical replicates were used for each sample allowing more accuracy in the final qRT-PCR amplification data which was run on a 7500 Fast Real Time PCR System (Applied Biosystems). This protocol has been detailed previously [ 21 ]. Following is the sequence of miRNAs:…”

Section: Methodsmentioning

confidence: 99%

Developing a panel of biomarkers and miRNA in patients with myocardial infarction for early intervention strategies of heart failure in West Virginian population

et al. 2018

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BackgroundMyocardial infarction is the most common cause of heart failure. MI has been intricately linked to ventricular remodeling, subsequently leading to the reduction in the cardiac ejection fraction causing HF. The cumulative line of evidence suggests an important role of several biomarkers in modulating the cardiac vasculature, further contributing towards the progression of post-MI complications. Studies have demonstrated, yet not fully established, that an important biomarker, IL-10, has a causal relationship with MI and associated cardiac dysfunction.HypothesisThis study aims to establish the role of IL-10 as a prognostic marker for the cardiovascular outcomes and to develop a panel of biomarkers and circulating miRNAs that could potentially result in the early detection of HF resulting from MI, allowing for early intervention strategies.Methods and resultsBlood was withdrawn and echocardiography assessment was performed on a total of 43 patients that were enrolled, within 24 hours of the incidence of MI. Patients were divided in three main groups, based on the ejection fraction measurement from echocardiography: control (n = 14), MI with normal EF (MI+NEF, n = 13) and MI with low EF (MI+LEF, n = 16). Our results showed that TGFβ-1, TNF-α, IL-6 and MMP-9 were upregulated significantly in MI+NEF group and more so in MI+LEF group, as compared to control group (p<0.01). The circulating levels of miR-34a, miR-208b and miR-126 were positively correlated and showed elevated levels in the MI+NEF group, even higher in MI+LEF group, while levels of miR-24 and miR-29a were reduced in MI+NEF, and much lower in MI+LEF, as compared to the control group (p<0.01). Our results also demonstrated a direct correlation of IL-10 with the ejection fraction in patients with MI: IL-10 was elevated in MI+NEF group, however, the levels were significantly low in MI+LEF group suggesting an important role of IL-10 in predicting heart failure. Importantly, our study confirmed the correlation of IL-10 with EF by our follow-up echocardiography assessment that was performed 2 months after the incidence of MI.ConclusionOur results support the clinical application of these serum biomarkers to develop a panel for appropriate prognosis and management of adverse cardiac remodeling and development of heart failure post-myocardial infarction.

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Section: Methodsmentioning

confidence: 99%

Developing a panel of biomarkers and miRNA in patients with myocardial infarction for early intervention strategies of heart failure in West Virginian population

et al. 2018

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“…miRNAs can act locally within tissues and cells to regulate mRNA expression, and, more recently, miRNAs have been shown to exist in the circulation protected from degradation in exosomes or by adherence to circulating proteins [ 31 , 32 ]. Levels of miRNAs in blood can fluctuate as a function of diseases such as diabetes and obesity [ 33 , 34 ]. Circulating miRNAs can be targeted for uptake by specific cell types and alter gene expression in the host cell [ 30 ], thus constituting a mechanism for inter-tissue communication.…”

Section: Discussionmentioning

confidence: 99%

Improved systemic metabolism and adipocyte biology in miR-150 knockout mice

Kang

Liu

et al. 2018

Metabolism

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Introduction: Short non-coding micro-RNAs (miRNAs) are post-transcriptional factors that directly regulate protein expression by degrading or inhibiting target mRNAs; however, the role of miRNAs in obesity and cardiometabolic disease remains unclarified. Based on our earlier study demonstrating that miR-150 influences lipid metabolism, we have studied effects of miR-150 on systemic metabolism and adipocyte biology. Materials and Methods: Metabolic phenotypes including body weight, food intake, body composition, glucose tolerance and insulin sensitivity were assessed in WT and global miR-150 KO male mice fed a high-fat diet. Molecular changes in epididymal adipose tissue were evaluated through qRT-PCR and Western blotting. Results: miR-150 KO mice displayed lower body weight characterized by a reduction in % fat mass while % lean mass was increased. Lower body weight was associated with reduced food consumption and an increase in circulating leptin concentrations, as well as enhanced insulin sensitivity and glucose tolerance compared with WT mice. Absence of miR-150 resulted in increased mTOR expression known to participate in increased leptin production leading to reduction of food intake. Expression of PGC-1α, another target gene of miR-150, was also increased together with upregulation of PPARα and glycerol kinase in adipose tissue as well as other genes participating in triglyceride degradation and lipid oxidation. Conclusion: miR-150 KO mice showed metabolic benefits accompanied by reduced body weight, decreased energy intake, and enhanced lipid metabolism. miR-150 may represent both a biomarker and novel therapeutic target regarding obesity and insulin resistance.

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“…Other biomarkers identified in the literature correlating MetS and NAFLD/NASH include: increased levels of IL-6, leptin, and TNF-α as well as decreased levels of adiponectin [ 89 – 91 ]. These markers have also been identified with similar trends that correlate with disease progression of MetS [ 29 , 92 – 96 ]. These trends in biomarkers between these two diseases outlines the value of noninvasive tests to identify disease progression MetS leading to NAFLD/NASH.…”

Section: Metabolic Syndromementioning

confidence: 90%

Investigating Molecular Connections of Non-alcoholic Fatty Liver Disease with Associated Pathological Conditions in West Virginia for Biomarker Analysis

Sharma

Lakhani

Klug

et al. 2017

J Clin Cell Immunol

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Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by a steatosis of the liver that may progress to more serious pathological conditions including: nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. As the prevalence of NAFLD has increased worldwide in recent years, pathophysiology and risk factors associated with disease progression of NAFLD are at the focus of many studies. NAFLD is related to and shares common serum biomarkers with cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome (MetS). West Virginia (WV) is a state with some of the highest rates of CVD, obesity and diabetes mellitus. As NAFLD is closely related to these diseases, it is of particular interest in WV. Currently there is no cost-effective, standardized method used clinically to detect NAFLD prior to the onset of reversible complications. At this time, the diagnosis of NAFLD is made with costly radiologic studies and invasive biopsy. These studies are only diagnostic once changes to hepatic tissue have occurred. The diagnosis of NAFLD by traditional methods may not allow for successful intervention and may not be readily available in areas with already sparse medical resources. In this literature review, we identify a list of biomarkers common among CVD, T2DM, obesity, MetS and NAFLD. From this research we propose the following biomarkers are good candidates for inclusion in a panel of biomarkers for the early detection of NAFLD: adiponectin, AST, ALT, apo-B, CK18, CPS1, CRP, FABP-1, ferritin, GGT, GRP78, HDL-C, IGF-1, IL-1β, 6, 8, 10, IRS-2PAI-1, leptin, lumican, MDA SREBP-1c and TNF-α. Creating and implementing a biomarker panel for the early detection and attenuation of NAFLD, prior to the onset of irreversible complication would provide maximum benefit and decrease the disease burden on the patients and healthcare system of WV.

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Existence of a Strong Correlation of Biomarkers and miRNA in Females with Metabolic Syndrome and Obesity in a Population of West Virginia

Cited by 28 publications

References 42 publications

Developing a panel of biomarkers and miRNA in patients with myocardial infarction for early intervention strategies of heart failure in West Virginian population

Developing a panel of biomarkers and miRNA in patients with myocardial infarction for early intervention strategies of heart failure in West Virginian population

Improved systemic metabolism and adipocyte biology in miR-150 knockout mice

Investigating Molecular Connections of Non-alcoholic Fatty Liver Disease with Associated Pathological Conditions in West Virginia for Biomarker Analysis

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