Abstract MP44: A Novel And 2 Known Differentially Expressed MicroRNAs Were Identified In Peripheral Blood Mononuclear Cells Of Patients With Hypertension Associated With Metabolic Syndrome

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Olga Berillo ◽  
Kugeng Huo ◽  
Julio C Fraulob-Aquino ◽  
Chantal Richer ◽  
Na Li ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Peripheral Blood Mononuclear Cells ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Target Organ ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Background: Hypertension (HTN) is associated with subclinical target organ damage including cardiac, vascular and kidney injury. The immune system plays a role in hypertension and target organ damage. Activation of T cells has been reported among peripheral blood mononuclear cells (PBMCs) of patients with HTN. MicroRNAs (miRNAs) are crucial post-transcriptional regulators of immune cells. Whether miRNAs play a role in the activation of immune cells in hypertension complicated by target organ damage in humans remains unknown. We aimed to address this question by identifying differentially expressed (DE) miRNAs and their mRNA targets in PBMCs of patients with hypertension complicated or not with metabolic syndrome (MetS) or chronic kidney disease (CKD). Methods: Normotensive subjects and patients with hypertension (HTN) associated or not with at least 2 other features of MetS or CKD were studied (n=15-16). PBMCs were isolated from blood, RNA extracted for small and total RNA sequencing (RNA-seq) using Illumina HiSeq-2500 and data were analyzed using a systems biology approach. MiRDeep2 was used for novel miRNAs prediction, miRNA annotation and counting. TargetScan 7.07 was used to predict DE miRNA targets with weighted context score percentile >50%. DE genes miRNAs and mRNAs were identified with fold change (FC) >1.5 and P <0.005. DE miRNAs with FC>2 and mean read count number (MRCM) >500, and with predicted targets with MRCM>300 were validated by reverse transcription-quantitative PCR (RT-qPCR). Results: DE miRNAs, mRNAs and non-coding RNAs were identified in HTN (22, 19 and 0), MetS (57, 401 and 11) and CKD (6, 26 and 2) compared to NTN. TargetScan predicted that 7 miRNAs target 3 mRNAs in NTN, 57 miRNAs target 55 mRNAs in MetS and 3 miRNAs target 2 mRNAs in CKD. DE miR-409-5p (FC: 0.54±0.10 vs 1.00±0.09, P <0.05), miR-411-5p (FC: 0.40±0.06, vs 1.00±0.11, P <0.001) and the novel miR-pl-86 (FC: 1.96±0.17 vs 1.00±0.15, P <0.05) in MetS vs NTN were validated by RT-qPCR. RNA-seq data were correlated with RT-qPCR for miR-409-5p (R 2 =0.40, P <2.4E-07, n=55), miR-411-5p (R 2 =0.55, P <1.1E-10, n=55), miR-pl-86 (R 2 =0.37, P <5.5E-07, n=56). Conclusion: This study showed that DE miR-409-5p, miR-411-5p and miR-pl-86 may play a role in HTN associated with MetS.

Abstract 4: Molecular Profile Of Peripheral Blood Mononuclear Cells In Hypertensive Adolescents With Target Organ Damage

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Fnu MOHAMMED ARIF ◽  
Elaine M Urbina ◽  
Sakthivel Sadayappan ◽  
Richard Becker
Keyword(s):  
Growth Factor ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Introduction: Primary hypertension (PH) is a multifactorial disease influenced by genetic, epigenetic, and environmental factors. Despite the occurrence of PH-associated cardiovascular events in youth, the molecular mechanism(s) of target organ damage (TOD) are unknown. Objectives: (1) To identify an epigenetic signature and gene expression profiles in adolescents with low blood pressure (BP) and normal left ventricular mass (LVM) compared to those with high BP and high LVM; and (2) to determine novel gene targets and associated signaling pathways for future investigation and intervention. Methods and Results: A total of 397 participants (mean age 15.6 ±1.7 years, 59% male, 63% Caucasian) were enrolled across the distribution of BP. The average daytime ambulatory systolic BP recorded in healthy and hypertensive participants was 112 ±9.71 and 133 ±7.2 mmHg ( p<0.05 ) respectively. Clinical measures revealed higher body mass index (26.8 ±7.02 vs 29.6 ±7.88 Kg/m 2 ; p<0.05 ), and abnormal circulatory HDL (47.4 ±12.1 vs 43.4 ±11.7 mg/dL; p<0.05 ), glucose (87.8 ±7.98 vs 90.8 ±8.17 mg/dL; p<0.05 ), insulin (17.8 ±14.3 vs 23.7 ±19 μIU/dL; p<0.05 ), creatinine (0.718 ±0.13 vs 0.727 ±0.17 mg/dL; p<0.05 ), uric acid (5.4 ±1.63 vs 6.04 ±1.52 mg/dL; p<0.05 ), CRP (1.35 ±1.8 vs 1.92 ±2.14 mg/dL; p<0.05 ), and left ventricular hypertrophy (LVM/ht 2.7 ; 31.4 ±6.74 vs 33.5 ±7.15 g/m 2.7 ; p<0.05 ), and arterial stiffness (Pulse wave velocity; 4.83 ±0.69 vs 5.35 ±0.92 m/sec; p<0.05 ). Using peripheral blood mononuclear cells, mRNA-Seq, miRNA-Seq, and whole-genome DNA methylation analysis revealed master genes, and regulatory pathways related to BP regulation, tissue fibrosis and cardiovascular remodeling. Our study reveals a novel PH-associated TOD mechanism, showing angiogenesis inhibition mediated by VASH1 (Vasohibin-1) upregulation and downtrends in VASH2 (Vasohibin-2), VEGFC (Vascular endothelial growth factor C), HIF1α (Hypoxia-inducible factor 1-alpha), and IGF1 (Insulin Like Growth Factor 1). Moreover, VASH1 targeting miRNA hsa-miR-30e-5p is inversely regulated. Conclusion: Angiogenesis inhibition in the presence of common demographic and clinical intermediate-phenotypes may contribute to the development of TOD in hypertensive youth.

Traditional Acupuncture Increases the Content of Beta-Endorphin in Immune Cells and Influences Mitogen Induced Proliferation

1991 ◽  
Vol 19 (02) ◽  
pp. 101-104 ◽  
Author(s):  
Mauro Bianchi ◽  
Edda Jotti ◽  
Paola Sacerdote ◽  
Alberto E. Panerai
Keyword(s):  
Immune Responses ◽  
T Lymphocyte ◽  
Peripheral Blood Mononuclear Cells ◽  
Immune Cells ◽  
Lymphocyte Proliferation ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Beta Endorphin ◽  
T Lymphocyte Proliferation ◽  
Blood Mononuclear Cells

We measured beta-endorphin concentrations in peripheral blood mononuclear cells and mitogen-induced T-lymphocyte proliferation in patient who underwent treatment with traditional acupuncture. Traditional acupuncture increased both the concentrations of the opioid in the immune cells and lymphocyte proliferation. Our data are consistent with the hypothesis that traditional acupuncture modulates immune responses in man.

scholarly journals Statin-induced microRNAome alterations modulating inflammation pathways of peripheral blood mononuclear cells in patients with hypercholesterolemia

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Hung-Ju Lin ◽  
Sung-Liang Yu ◽  
Ta-Chen Su ◽  
Hsiu-Ching Hsu ◽  
Ming-Fong Chen ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Density Lipoprotein ◽  
Cardiovascular Risks ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Abstract Statins inhibit cholesterol biogenesis and modulate atheroma inflammation to reduce cardiovascular risks. Promoted by immune and non-immune cells, serum C-reactive protein (CRP) might be a biomarker suboptimal to assess inflammation status. Although it has been reported that statins modulated inflammation via microRNAs (miRNAs), evidence remains lacking on comprehensive profiling of statin-induced miRNAome alterations in immune cells. We recruited 19 hypercholesterolemic patients receiving 2 mg/day pitavastatin and 15 ones receiving 10 mg/day atorvastatin treatment for 12 weeks, and performed microarray-based profiling of 1733 human mature miRNAs in peripheral blood mononuclear cells (PBMCs) before and after statin treatment. Differentially expressed miRNAs were determined if their fold changes were &gt;1.50 or &lt;0.67, after validated using quantitative polymerase chain reaction (qPCR). The miRSystem and miTALOS platforms were utilized for pathway analysis. Of the 34 patients aged 63.7 ± 6.2 years, 27 were male and 19 were with coronary artery disease. We discovered that statins induced differential expressions of miR-483-5p, miR-4667-5p, miR-1244, and miR-3609, with qPCR-validated fold changes of 1.74 (95% confidence interval, 1.33–2.15), 1.61 (1.25–1.98), 1.61 (1.01–2.21), and 1.68 (1.19–2.17), respectively. The fold changes of the four miRNAs were not correlated with changes of low-density-lipoprotein cholesterol or CRP, after sex, age, and statin type were adjusted. We also revealed that RhoA and transforming growth factor-β signaling pathways might be regulated by the four miRNAs. Given our findings, miRNAs might be involved in statin-induced inflammation modulation in PBMCs, providing likelihood to assess and reduce inflammation in patients with atherosclerotic cardiovascular diseases.

Norepinephrine Inhibits Energy Metabolism of Human Peripheral Blood Mononuclear Cells via Adrenergic Receptors

2001 ◽  
Vol 21 (5) ◽  
pp. 627-635 ◽  
Author(s):  
Jan D. Lünemann ◽  
Frank Buttgereit ◽  
Robert Tripmacher ◽  
Christoph G. O. Baerwald ◽  
Gerd-Rüdiger Burmester ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Peripheral Blood Mononuclear Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Adrenergic Receptors ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Immune Effector ◽  
Blood Mononuclear Cells

Previous studies demonstrated that the adaptive response to stressors and inflammatory signals involves the activation of the automotic nervous system. Catecholamines have been shown to modulate the activity of various immune effector cells directly via membrane adrenergic receptors. Here, we investigated immediate effects of norepinephrine on energy metabolism of immune cells. Norepinephrine inhibits oxygen consumption of human peripheral blood mononuclear cells at concentrations that are relevant to its physiological range. The ?-adrenoreceptor antagonist propranolol, but not the ?-adrenoreceptor antagonist phentolamine reversed the norepinephrine induced inhibition in quiescent cells. Conversely, phentolamine but not propranolol is capable of blocking norepinephrine mediated effects in mitogen activated human peripheral blood mononuclear cells. Our data indicate that the sensitization of ?- and ?-adrenoreceptors on immune cells is differentially regulated, and that these processes depend on the activation state of these cells. These findings have important implications for the understanding of stress-induced suppression of immune function and may contribute to the elucidation of the pathogenesis of immunologically mediated diseases.

scholarly journals RNA-Seq Transcriptome Analysis Reveals Long Terminal Repeat Retrotransposon Modulation in Human Peripheral Blood Mononuclear Cells after In Vivo Lipopolysaccharide Injection

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Maria Paola Pisano ◽  
Olivier Tabone ◽  
Maxime Bodinier ◽  
Nicole Grandi ◽  
Julien Textoris ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Ltr Retrotransposon ◽  
Ltr Retrotransposons ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

ABSTRACT Human endogenous retroviruses (HERVs) and mammalian apparent long terminal repeat (LTR) retrotransposons (MaLRs) are retroviral sequences that integrated into germ line cells millions of years ago. Transcripts of these LTR retrotransposons are present in several tissues, and their expression is modulated in pathological conditions, although their function remains often far from being understood. Here, we focused on the HERV/MaLR expression and modulation in a scenario of immune system activation. We used a public data set of human peripheral blood mononuclear cells (PBMCs) RNA-Seq from 15 healthy participants to a clinical trial before and after exposure to lipopolysaccharide (LPS), for which we established an RNA-Seq workflow for the identification of expressed and modulated cellular genes and LTR retrotransposon elements. IMPORTANCE We described the HERV and MaLR transcriptome in PBMCs, finding that about 8.4% of the LTR retrotransposon loci were expressed and identifying the betaretrovirus-like HERVs as those with the highest percentage of expressed loci. We found 4,607 HERV and MaLR loci that were modulated as a result of in vivo stimulation with LPS. The HERV-H group showed the highest number of differentially expressed most intact proviruses. We characterized the HERV and MaLR loci as differentially expressed, checking their genomic context of insertion and observing a general colocalization with genes that are involved and modulated in the immune response, as a consequence of LPS stimulation. The analyses of HERV and MaLR expression and modulation show that these LTR retrotransposons are expressed in PBMCs and regulated in inflammatory settings. The similar regulation of HERVs/MaLRs and genes after LPS stimulation suggests possible interactions of LTR retrotransposons and the immune host response.

scholarly journals An Isocaloric Nordic Diet Modulates RELA and TNFRSF1A Gene Expression in Peripheral Blood Mononuclear Cells in Individuals with Metabolic Syndrome—A SYSDIET Sub-Study

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2932 ◽  
Author(s):  
Stine M. Ulven ◽  
Kirsten B. Holven ◽  
Amanda Rundblad ◽  
Mari C. W. Myhrstad ◽  
Lena Leder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Control Diet ◽  
Peripheral Blood Mononuclear ◽  
Nordic Diet ◽  
Blood Mononuclear Cells

A healthy dietary pattern is associated with a lower risk of metabolic syndrome (MetS) and reduced inflammation. To explore this at the molecular level, we investigated the effect of a Nordic diet (ND) on changes in the gene expression profiles of inflammatory and lipid-related genes in peripheral blood mononuclear cells (PBMCs) of individuals with MetS. We hypothesized that the intake of an ND compared to a control diet (CD) would alter the expression of inflammatory genes and genes involved in lipid metabolism. The individuals with MetS underwent an 18/24-week randomized intervention to compare a ND with a CD. Eighty-eight participants (66% women) were included in this sub-study of the larger SYSDIET study. Fasting PBMCs were collected before and after the intervention and changes in gene expression levels were measured using TaqMan Array Micro Fluidic Cards. Forty-eight pre-determined inflammatory and lipid related gene transcripts were analyzed. The expression level of the gene tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) was down-regulated (p = 0.004), whereas the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit, RELA proto-oncogene, was up-regulated (p = 0.016) in the ND group compared to the CD group. In conclusion, intake of an ND in individuals with the MetS may affect immune function.

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