Autocrine/Paracrine Role of Inflammation-Mediated Calcitonin Gene-Related Peptide and Adrenomedullin Expression in Human Adipose Tissue

Linscheid, Philippe; Seboek, Dalma; Zulewski, Henryk; Keller, Ulrich; Müller, Beat

doi:10.1210/en.2004-1424

Cited by 171 publications

(107 citation statements)

References 52 publications

(61 reference statements)

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“…Obese population (nZ13) synthetize AM before differentiation when stimulated by proinflammatory cytokines (16). These observations emphasize the importance of the stromal portion of the adipose tissue as a site of adipokine production, as previously reported (27).…”

Section: Lean Population (Nz9)supporting

confidence: 76%

“…We performed a partial identification of other stromal cell types involved in AM synthesis. It is known that macrophages, frequently present in adipose tissue (25), produce AM in vitro (16,26). Our results demonstrate that AM and CD 68 proteins were colocalized, strongly suggesting that macrophages within adipose tissue can synthesize AM.…”

Section: Discussionsupporting

confidence: 62%

“…One can suggest that adipose AM may interplay with the features of the proinflammatory state which is usually present in the metabolic syndrome. Indeed, it was shown that lipopolysaccharide (LPS) stimulates AM mRNA expression in cultured macrophages (31), in undifferentiated human mesenchymal stem cells (16), and in fibroblasts Hs68 (32). Our findings, showing a positive relationship between OM tissue AM-IR and circulating PAI-1 levels and between OM AM and TNFa mRNAs, argue for a connection between AM and inflammation within adipose tissue.…”

Section: Lean Population (Nz9)supporting

confidence: 51%

“…Recent studies showed, using real time (RT)-PCR, that AM mRNA is present in human adipose tissue collected during surgery (15,16), and that AM peptide is produced by isolated human adipocytes (14), exposed to an inflammatory environment (16). Identically, human mesenchymal stem cell-derived adipocytes express AM in response to proinflammatory cytokines (16).…”

Section: Introductionmentioning

confidence: 99%

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Expression of adrenomedullin in adipose tissue of lean and obese women

et al. 2006

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Objective: Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide, was shown recently to be expressed by adipose tissue. The aim of our study was to investigate the precise localization of AM within human adipose tissue, and to examine AM regulation in obesity. Design: Subcutaneous (SC) and omental (OM) adipose tissues from 9 lean and 13 obese women were profiled for AM expression changes. Preadipocytes from human adipose tissue were isolated and differentiated under defined adipogenic conditions. Methods: AM expression was analyzed by immunohistochemistry, in situ hybridization and quantitative RT-PCR. Results: A strong AM expression was observed in vessel walls, stromal cell clusters and isolated stromal cells, some of them being CD 68 positive, whereas mature adipocytes were not labeled. Calcitonin receptor-like receptor and receptor activity-modifying proteins (RAMP) 2 and RAMP 3 were expressed in vessel walls. In vitro, preadipocytes of early differentiation stages spontaneously secreted AM. No difference in AM localization was found between SC and OM adipose tissue. AM levels in SC tissue did not differ between lean and obese subjects. By contrast, AM levels in OM tissue were significantly higher in obese as compared with lean women. Moreover, we found a positive relationship between OM AM and tumor necrosis factor a mRNA levels and AM-immunoreactive area in OM tissue followed the features of the metabolic syndrome. Conclusion: Stromal cells from human adipose tissue, including macrophages, produce AM. Its synthesis increased in the OM territory during obesity and paralleled the features of the metabolic syndrome. Therefore, AM should be considered as a new member of the adipokine family.

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Section: Lean Population (Nz9)supporting

confidence: 76%

Section: Discussionsupporting

confidence: 62%

Section: Lean Population (Nz9)supporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

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Expression of adrenomedullin in adipose tissue of lean and obese women

et al. 2006

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“…It is known that ADM can behave both as a hormone and a cytokine. 26 The inclusion of concomitant comorbidities might complicate the effect of ADM on COPD and confuse its actions on survival. Consequently, we hypothesized that the missing predictive potential of ADM in our work was probably caused by a low prevalence of comorbidities in subjects with COPD exacerbation.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and Prognostic Value of Plasma Adrenomedullin in COPD Exacerbation

Meng

Song

et al. 2014

Respir Care

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BACKGROUND: Adrenomedullin (ADM) is a regulatory peptide with many biological actions, but little is known about its role in patients with COPD exacerbation. The purpose of this study was to evaluate the diagnostic and prognostic value of plasma ADM levels on hospital admission in patients with COPD exacerbation. METHODS: Consecutive subjects admitted to the hospital for COPD exacerbation were included and were followed up for 1 y; in addition, subjects with stable COPD from an out-patient clinic and healthy volunteers were recruited as controls. RESULTS: Compared with healthy subjects (145 pg/mL [interquartile range {IQR} 103-290 pg/mL]), plasma ADM levels were significantly higher in subjects with COPD exacerbation (270 pg/mL [IQR 170 -510 pg/mL], P ‫؍‬ .001) and in subjects with stable COPD (400 pg/mL [IQR 210 -525 pg/mL], P < .001). In subjects with COPD exacerbation, ADM levels were significantly elevated during exacerbation (560 pg/mL [IQR 495-630 pg/mL]) compared with the recovery phase (470 pg/mL [IQR 393-553 pg/mL], P ‫؍‬ .01) and the stable phase (200 pg/mL [IQR 143-308 pg/mL], P < .001). In receiver operating characteristic analysis, in subjects with COPD exacerbation, ADM had high diagnostic accuracy in differentiating between exacerbation and the stable phase (area under the curve 0.97, 95% CI 0.93-1.02, P < .001). In Cox regression analysis, plasma ADM was not independently associated with 1-y survival (P ‫؍‬ .97), but it could accurately predicted the need for ICU care (hazard ratio 1.37, 95% CI 1.09 -1.72, P ‫؍‬ .008). CONCLUSIONS: Plasma ADM is a valuable biomarker to confirm COPD exacerbation; furthermore, plasma ADM independently predicts the need of ICU care, although it is not associated with long-term mortality in patients with COPD exacerbation.

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Procalcitonin Algorithms for Antibiotic Therapy Decisions

Schuetz

Chiappa²,

Briel³

et al. 2011

Arch Intern Med

337

125

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Previous randomized controlled trials suggest that using clinical algorithms based on procalcitonin levels, a marker of bacterial infections, results in reduced antibiotic use without a deleterious effect on clinical outcomes. However, algorithms differed among trials and were embedded primarily within the European health care setting. Herein, we summarize the design, efficacy, and safety of previous randomized controlled trials and propose adapted algorithms for US settings. We performed a systematic search and included all 14 randomized controlled trials (N = 4467 patients) that investigated procalcitonin algorithms for antibiotic treatment decisions in adult patients with respiratory tract infections and sepsis from primary care, emergency department (ED), and intensive care unit settings. We found no significant difference in mortality between procalcitonin-treated and control patients overall (odds ratio, 0.91; 95% confidence interval, 0.73-1.14) or in primary care (0.13; 0-6.64), ED (0.95; 0.67-1.36), and intensive care unit (0.89; 0.66-1.20) settings individually. A consistent reduction was observed in antibiotic prescription and/or duration of therapy, mainly owing to lower prescribing rates in low-acuity primary care and ED patients, and shorter duration of therapy in moderate- and high-acuity ED and intensive care unit patients. Measurement of procalcitonin levels for antibiotic decisions in patients with respiratory tract infections and sepsis appears to reduce antibiotic exposure without worsening the mortality rate. We propose specific procalcitonin algorithms for low-, moderate-, and high-acuity patients as a basis for future trials aiming at reducing antibiotic overconsumption.

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Autocrine/Paracrine Role of Inflammation-Mediated Calcitonin Gene-Related Peptide and Adrenomedullin Expression in Human Adipose Tissue

Cited by 171 publications

References 52 publications

Expression of adrenomedullin in adipose tissue of lean and obese women

Expression of adrenomedullin in adipose tissue of lean and obese women

Diagnostic and Prognostic Value of Plasma Adrenomedullin in COPD Exacerbation

Procalcitonin Algorithms for Antibiotic Therapy Decisions

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