150 Low plasma concentrations of apolipoprotein m correlate to disease activity and endothelial dysfunction in sle

The aim of our study was to evaluate if endothelial-dysfunction (ED) occurs in patients with primary Sjogren syndrome (pSS) and whether it is associated with the disease characteristics and activity. A total of 46 patients with pSS and 30 controls, without known cardiovascular disease, were enrolled in this study. A flow-mediated-dilation (FMD) of the brachial artery, plasma concentrations of the nitric oxide (NO) metabolic pathway (ADMA, L-arginine, SDMA, cGMP), and markers of endothelial inflammatory function (PAI-1, sE-selectin) and angiogenesis (angiostatin, VEGF) were analyzed. The FMD was significantly lower in pSS patients (7.56 ± 3.08 vs. 10.91 ± 1.02%, p = 0.043) and positively correlated with the Ro/SS-A-antibodies (r = 0.34, p = 0.03), pulmonary involvement (r = 0.52, p = 0.001) and inversely with ADMA (r = −0.35, p = 0.04). Plasma ADMA, L-arginine and angiostatin levels were significantly higher in pSS patients (0.39 ± 0.08 vs. 0.36 ± 0.06 µmol/L, p = 0.05; 29.07 ± 6.7 vs. 25.4 ± 5.23 µmol/L, p = 0.01; 152.25 ± 60.99 vs. 120.07 ± 38.7 pg/mL, p = 0.0, respectively). ADMA was associated with ESSDAI (r = 0.33, p = 0.02), SCORE (r = 0.57, p = 0.00003) and focus score (r = 0.38, p = 0.04). In the multiple regression analysis, the ESSDAI was significantly and independently associated with plasma ADMA levels (β = 0.24, p = 0.04). Moreover, plasma cGMP concentrations were negatively correlated with the disease duration (r = −0.31, p = 0.03). Endothelial function is impaired in patients with pSS and associated with the measures of disease activity, which supports the key-role of inflammation in developing and maintaining accelerated atherosclerosis.

Download Full-text

Drug−disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity

British Journal of Clinical Pharmacology ◽

10.1111/j.1365-2125.2011.04019.x ◽

2011 ◽

Vol 72 (5) ◽

pp. 787-797 ◽

Cited By ~ 14

Author(s):

Forough Sanaee ◽

John D. Clements ◽

Alistair W. G. Waugh ◽

Richard N. Fedorak ◽

Richard Lewanczuk ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Plasma Concentrations

Download Full-text

Plasma concentrations of complement-activation complexes correlate with disease activity in patients diagnosed with isolated central nervous system vasculitis1

Journal of Allergy and Clinical Immunology ◽

10.1016/0091-6749(89)90472-7 ◽

1989 ◽

Vol 83 (1) ◽

pp. 11-16 ◽

Cited By ~ 13

Author(s):

P LANGLOIS ◽

G SHARON ◽

M GAWRYL

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Disease Activity ◽

Complement Activation ◽

Plasma Concentrations

Download Full-text

Diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction

American Journal of Clinical Nutrition ◽

10.1093/ajcn/82.1.163 ◽

2005 ◽

Vol 82 (1) ◽

pp. 163-173 ◽

Cited By ~ 429

Author(s):

Teresa T Fung ◽

Marjorie L McCullough ◽

PK Newby ◽

JoAnn E Manson ◽

James B Meigs ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Diet Quality ◽

Plasma Concentrations ◽

Markers Of Inflammation

Download Full-text

Abstract 034: Characterization of A Novel Maternally Restricted Pro-angiogenic Therapeutic for Preeclampsia

Hypertension ◽

10.1161/hyp.68.suppl_1.034 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

William H Stewart ◽

Eric George ◽

Gene L Bidwell ◽

Heather Chapman ◽

Fakhri Mahdi ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Half Life ◽

Plasma Concentrations ◽

Subcutaneous Administration ◽

Chronic Administration ◽

Health Concern ◽

Pathogenic Factors ◽

Clearance Kinetics

Background: Preeclampsia is a major obstetrical health concern, affecting 5-8% of all pregnancies. Hallmarked by hypertension and endothelial dysfunction the origin of the disease remains obscure, though it is generally accepted that placental insufficiency/ischemia is a central cause. In response, the placenta secretes pathogenic factors, in particular the anti-angiogenic protein sFlt-1. Currently, there is no effective therapy for the management of the preeclampsia patient. We have recently produced a novel synthetic peptide based on placental growth factor (PlGF) which is maternally restricted by fusion to the synthetic carrier elastin like polypeptide (ELP). Here, we describe its in vivo pharmacokinetics and biodistribution. Methods: Fluorescently labeled ELP-PLGF was administered i.v. and blood sampled serially to determine clearance kinetics. Long-term pharmacokinetics and biodistribution was performed after subcutaneous administration of labeled peptide. Measurements were made on serially drawn blood, and in the whole animal by in vivo imaging. Results: ELP-PlGF exhibited markedly more favorable pharmacokinetics than the normal half life of PlGF, with a terminal half-life of ~10 hours as opposed to ~30 minutes for PlGF alone. Chronic administration found highest levels accumulating in placenta and kidney (two favorable targets for preeclampsia) and liver. A single subcutaneous administration at 100mg/kg resulted in sustained therapeutic plasma concentrations for over 10 days. Conclusion: These data demonstrate that ELP-PlGF has favorable pharmacokinetic and biodistribution profiles. Previous data suggest ELP-PlGF directly antagonizes sFlt-1 in culture. Future studies to assess the in vivo effectiveness of ELP-PlGF in managing placental ischemia induced hypertension and endothelial dysfunction are currently in progress. Acknowledgment: This work was supported by NIH grants R0121527 (GLB), T32HL105324 (OCL), P01HL51971, P20GM104357 (EMG), and R00HL116774 (EMG)

Download Full-text

Utility of Select Plasma MicroRNA for Disease and Cardiovascular Risk Assessment in Patients with Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.150232 ◽

2015 ◽

Vol 42 (10) ◽

pp. 1746-1751 ◽

Cited By ~ 25

Author(s):

Michelle J. Ormseth ◽

Joseph F. Solus ◽

Kasey C. Vickers ◽

Annette M. Oeser ◽

Paolo Raggi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Coronary Artery ◽

Disease Activity ◽

Coronary Artery Calcium ◽

Noncoding Rna ◽

Coronary Artery Calcium Score ◽

Subclinical Atherosclerosis ◽

Plasma Concentrations ◽

Calcium Score ◽

Plasma Mirna

Objective.MicroRNA (miRNA) are small noncoding RNA that posttranscriptionally regulate gene expression and serve as potential mediators and markers of disease. Recently, plasma miR-24-3p and miR-125a-5p concentrations were shown to be elevated in rheumatoid arthritis (RA) and useful for RA diagnosis. We assessed the utility of 7 candidate plasma miRNA, selected for biological relevance, for RA diagnosis and use as markers of disease activity and subclinical atherosclerosis in RA.Methods.The cross-sectional study included 168 patients with RA and 91 control subjects of similar age, race, and sex. Plasma concentrations of miR-15a-5p, miR-24-3p, miR-26a-5p, miR-125a-5p, miR-146a-5p, miR-155-5p, and miR-223-3p were measured by quantitative PCR. Utility of plasma miRNA concentrations for RA diagnosis was assessed by area under the receiver-operating characteristic curve (AUROC). Associations between plasma miRNA concentrations and RA disease activity and coronary artery calcium score were assessed by Spearman correlations.Results.Plasma concentrations of miR-15a-5p, miR-24-3p, miR-26a-5p, miR-125a-5p, miR-146a-5p, miR-155-5p, and miR-223-3p were significantly increased in patients with RA. The highest AUROC for diagnosis of RA (AUROC = 0.725) was found in miR-24-3p, including among rheumatoid factor–negative patients (AUROC = 0.772). Among all patients with RA, the combination of miR-24-3p, miR-26a-5p, and miR-125a-5p improved the model modestly (AUROC = 0.747). One miRNA, miR-155-5p, was weakly inversely associated with swollen joint count (p = 0.024), but no other miRNA were associated with disease activity or coronary artery calcium score.Conclusion.The combination of miR-24-3p, miR-26a-5p, and miR-125a-5p had the strongest diagnostic accuracy for RA. Candidate miRNA had little or no association with RA disease activity or subclinical atherosclerosis.

Download Full-text