Peripheral blood miRNAs as a biomarker for chronic cardiovascular diseases.
Ontology highlight
ABSTRACT:
SUBMITTER: Jiang Y
PROVIDER: S-EPMC4052773 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:BackgroundFrailty syndrome is characterized by multisystem dysregulation frequently found in older individuals or even in younger patients with chronic disabling diseases such as cardiovascular diseases.ObjectiveTo determine whether peripheral blood cell count, and its subpopulations, red blood cell and platelets, morphology and different ratios (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and red blood distribution width-to-platelet ratio) are associated with cardiac frail patients, and through this to improve the prediction of frailty status in patients with cardiovascular diseases.MethodsAn observational, retrospective, cohort study enrolling 179 patients with cardiovascular disease divided into two groups: non-frail group (100 pts) and frail group (79 pts), a cohort detached from the Frail.RO study. The frailty was evaluated based on the Fried criteria; haematological markers, sociodemographic data, and variables related to cardiovascular diseases and comorbidities were also recorded.ResultsLower lymphocytes, platelet count, and neutrophil-to-lymphocyte ratio were significantly associated with a more severe frailty syndrome. Regarding red blood cells, haemoglobin concentration and red cell distribution width significantly correlated with the severity of the frailty syndrome. Receiver operating characteristic curve analysis for these markers associated with the frailty syndrome revealed an acceptable sensitivity of 66 % and specificity of 65% to identify frail individuals. Malnutrition and hypercholesterolemia are relevant predictors for identifying frailty in hospitalized cardiovascular patients.ConclusionThe evaluation of peripheral blood cell composition routinely measured in clinical practice can represent a valuable, but limited indicator, to diagnose frailty syndrome and eventually, the effects of interventions in frail patients with cardiovascular diseases.
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Project description:Mechanistic/mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase of the phosphoinositide 3-kinase- (PI3K-) related kinase family, elicits a vital role in diverse cellular processes, including cellular growth, proliferation, survival, protein synthesis, autophagy, and metabolism. In the cardiovascular system, the mTOR signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of both physiological and pathological processes. MicroRNAs (miRs), a class of short noncoding RNA, are an emerging intricate posttranscriptional modulator of critical gene expression for the development and maintenance of homeostasis across a wide array of tissues, including the cardiovascular system. Over the last decade, numerous studies have revealed an interplay between miRNAs and the mTOR signaling circuit in the different cardiovascular pathophysiology, like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation, and atherosclerosis. In this review, we provide a comprehensive state of the current knowledge regarding the mechanisms of interactions between the mTOR signaling pathway and miRs. We have also highlighted the latest advances on mTOR-targeted therapy in clinical trials and the new perspective therapeutic strategies with mTOR-targeting miRs in cardiovascular diseases.
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Project description:BackgroundIn recent years, an increasing number of studies have proved that circulating miRNAs could be used for the early diagnosis of cardiovascular diseases and even play vital roles in the evaluation of therapeutic effects or prognosis. This study was conducted to examine the correlation between serum microRNAs and hyperlipidemia to provide a theoretical basis for the early screening and intervention of atherosclerotic cardiovascular diseases (ASCVD).MethodsThe serum samples and clinical data of 122 patients with hyperlipidemia and 168 healthy subjects were collected. Related clinical information was statistically analyzed for the two groups. Expression of circulating miRNAs was detected by miRNA microarray analysis and further verified by reverse transcription-quantitative PCR (RT-qPCR).ResultsStatistical analysis of clinical information revealed a significant difference in the incidence of ASCVD between the two groups. The MiRNA microarray analysis (n = 10) showed 22 miRNAs with significantly different expression, among which 12 showed upregulation, and the others showed downregulation. Those possessing obvious differences and stable expression in the miRNA microarray, including miRNA-191-3p, miRNA-933, and miRNA-425-3p, were chosen for further investigation using RT-qPCR. The results demonstrated that several miRNAs were related to lipid metabolism disorders, especially miRNA-933. The area under the curve (AUC) of miRNA-933 in distinguishing the hyperlipidemia and ASCVD patients was 0.739 (95% CI, 0.682-0.795; P < 0.01) and 0.703 (95% CI, 0.643-0.763, P < 0.01), respectively.ConclusionsIn conclusion, miRNA-191-3p, miRNA-933, and miRNA-425-3p may be depressed in the peripheral circulation of patients with lipid metabolism disorders (mainly LDL). Circulating miRNA-933 could be a feasible predictor for ASCVD at the early stage.
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Project description:The human microbiota contains microorganisms found on the skin, mucosal surfaces and in other tissues. The major component, the gut microbiota, can be influenced by diet, genetics, and environmental factors. Any change in its composition results in pathophysiological changes that can further influence the evolution of different conditions, including cardiovascular diseases (CVDs). The microbiome is a complex ecosystem and can be considered the metagenome of the microbiota. MicroRNAs (miRNAs) are speculated to interact with the intestinal microbiota for modulating gene expressions of the host. miRNAs represent a category of small non-coding RNAs, consisting of approximately 22 nucleotides, which can regulate gene expression at post-transcriptional level, by influencing the degradation of mRNA and modifying protein amounts. miRNAs display a multitude of roles, being able to influence the pathogenesis and progression of various diseases. Circulating miRNAs are stable against degradation, due to their enclosure into extracellular vesicles (EVs). This review aims to assess the current knowledge of the possible interactions between gut microbiota, miRNAs, and CVDs. As more scientific research is conducted, it can be speculated that personalized patient care in the future may include the management of gut microbiota composition and the targeted treatment against certain expression of miRNAs.
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Project description:Cardiovascular diseases (CVDs) are devastating disorders and the leading cause of mortality worldwide. The pathophysiology of cardiovascular diseases is complex and multifactorial and, in the past years, mitochondrial dysfunction and excessive production of reactive oxygen species (ROS) have gained growing attention. Indeed, CVDs can be considered as a systemic alteration, and understanding the eventual implication of circulating blood cells peripheral blood mononuclear cells (PBMCs) and or platelets, and particularly their mitochondrial function, ROS production, and mitochondrial DNA (mtDNA) releases in patients with cardiac impairments, appears worthwhile. Interestingly, reports consistently demonstrate a reduced mitochondrial respiratory chain oxidative capacity related to the degree of CVD severity and to an increased ROS production by PBMCs. Further, circulating mtDNA level was generally modified in such patients. These data are critical steps in term of cardiac disease comprehension and further studies are warranted to challenge the possible adjunct of PBMCs' and platelets' mitochondrial dysfunction, oxidative stress, and circulating mtDNA as biomarkers of CVD diagnosis and prognosis. This new approach might also allow further interesting therapeutic developments.
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Project description:IntroductionMicroRNAs may be implicated in the acquisition of drug resistance in chronic myeloid leukemia as they regulate the expression of not only BCR-ABL1 but also genes associated with the activation of drug transfer proteins or essential signaling pathways.MethodsTo understand the impact of specifically expressed miRNAs in chronic myeloid leukemia and their target genes, we collected peripheral blood mononuclear cells (PBMC) from patients diagnosed with chronic myeloid leukemia (CML) and healthy donors to determine whole miRNA expression by small RNA sequencing and screened out 31 differentially expressed microRNAs (DE-miRNAs) with high expression. With the utilization of miRNA set enrichment analysis tools, we present here a comprehensive analysis of the relevance of DE-miRNAs to disease and biological function. Furthermore, the literature-based miRNA-target gene database was used to analyze the overall target genes of the DE-miRNAs and to define their associated biological responses. We further integrated DE-miRNA target genes to identify CML miRNA targeted gene signature singscore (CMTGSS) and used gene-set enrichment analysis (GSEA) to analyze the correlation between CMTGSS and Hallmark gene-sets in PBMC samples from clinical CML patients. Finally, the association of CMTGSS stratification with multiple CML cell lineage gene sets was validated in PBMC samples from CML patients using GSEA.ResultsAlthough individual miRNAs have been reported to have varying degrees of impact on CML, overall, our results show that abnormally upregulated miRNAs are associated with apoptosis and aberrantly downregulated miRNAs are associated with cell cycle. The clinical database shows that our defined DE-miRNAs are associated with the prognosis of CML patients. CMTGSS-based stratification analysis presented a tendency for miRNAs to affect cell differentiation in the blood microenvironment.ConclusionCollectively, this study defined differentially expressed miRNAs by miRNA sequencing from clinical samples and comprehensively analyzed the biological functions of the differential miRNAs in association with the target genes. The analysis of the enrichment of specific myeloid differentiated cells and immune cells also suggests the magnitude and potential targets of differentially expressed miRNAs in the clinical setting. It helps us to make links between the different results obtained from the multi-faceted studies to provide more potential research directions.
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Project description:Chronic inflammatory diseases, such as inflammatory bowel disease—namely, Crohn’s disease and ulcerative colitis—psoriasis, multiple sclerosis, rheumatoid arthritis, and many others affect millions of people worldwide, causing a high burden of disease, socioeconomic impact, and healthcare cost. These diseases have common features including autoimmune pathogenesis and frequent co morbidity. The treatment of these chronic inflammatory diseases usually requires long-term immunosuppressive therapies with undesirable side effects. The future of chronic inflammatory disease prevention, detection, and treatment will be greatly influenced by the use of more effective biomarkers with enhanced performance. Given the practical issues of collecting tissue samples in inflammatory diseases, biomarkers derived from body fluids have great potential for optimized patient management through the circumvention of the abovementioned limitations. In this chapter, peripheral blood, urine, and cerebrospinal fluid biomarkers used in chronic inflammatory conditions are reviewed. In detail, this chapter reviews biomarkers to fore used or emerging to be used in patients with chronic inflammatory conditions. Those include inflammatory bowel diseases, chronic inflammatory conditions of the liver, biliary tract, pancreas, psoriasis, atopic disease, inflammatory skin diseases, rheumatic diseases, demyelination, and also the chronic inflammatory component of various other diseases in general medicine—including diabetes, cardiovascular disease, renal disease, and chronic obstructive pulmonary disease. Development of personalized medicine is closely linked to biomarkers, which may serve as the basis for diagnosis, drug discovery, and monitoring of diseases.
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Project description:BackgroundEndothelial dysfunction is involved in several cardiovascular diseases. Elevated levels of circulating endothelial cells (CECs) and low levels of endothelial progenitor cells (EPCs) have been described in different cardiovascular conditions, suggesting their potential use as diagnostic biomarkers for endothelial dysfunction. Compared to typical peripheral blood leukocyte subsets, CECs and EPCs occur at very low frequency. The reliable identification and characterization of CECs and EPCs is a prerequisite for their clinical use, however, a validated method to this purpose is still missing but a key for rare cell events.ObjectivesTo establish a validated flow cytometric procedure in order to quantify CECs and EPCs in human whole blood.MethodsIn the establishment phase, the assay sensitivity, robustness, and the sample storage conditions were optimized as prerequisite for clinical use. In a second phase, CECs and EPCs were analyzed in heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction, in arterial hypertension (aHT), and in diabetic nephropathy (DN) in comparison to age-matched healthy controls.ResultsThe quantification procedure for CECs and EPCs showed high sensitivity and reproducibility. CEC values resulted significantly increased in patients with DN and HFpEF in comparison to healthy controls. CEC quantification showed a diagnostic sensitivity of 90% and a sensitivity of 68.0%, 70.4%, and 66.7% for DN, HFpEF, and aHT, respectively.ConclusionA robust and precise assay to quantify CECs and EPCs in pre-clinical and clinical studies has been established. CEC counts resulted to be a good diagnostic biomarker for DN and HFpEF.
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