Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats

Itoh, Takefumi; Obata, Hiroaki; Murakami, Shigetaka; Hamada, Kaoru; Kangawa, Kenji; Kimura, Hiroshi; Nagaya, Noritoshi

doi:10.1152/ajplung.00412.2005

Cited by 67 publications

(61 citation statements)

References 55 publications

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“…In particular, adrenomedullin may decrease infection-induced organ damage, 5 inflammation, and apoptosis. 3 Our observational design cannot unravel this protective role, yet we confirm previous observations that high MR-proADM levels add a prognostic marker in patients clinically deemed to be high risk for death.…”

Section: Psi Class IIIsupporting

confidence: 83%

“…1 Adrenomedullin is a peptide produced by multiple tissue types during physiologic stress, and has pluripotent function, including vasodilatory, antimicrobial, and antiinflammatory activity. 2 In animal models of sepsis, [3][4][5] exogenous adrenomedullin reduces acute lung injury, vascular permeability, and death; endogenous overexpression similarly ameliorates the septic insult. Human data are sparse, but early studies 6,7 reported high adrenomedullin levels associated with increased vasodilation and severity of illness in systemic inflammation and septic shock.…”

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confidence: 99%

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Midregional Proadrenomedullin as a Prognostic Tool in Community-Acquired Pneumonia

Huang

Angus

Kellum

et al. 2009

Chest

125

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Background: Midregional proadrenomedullin (MR-proADM) is a potential prognostic biomarker in patients with community-acquired pneumonia (CAP). Previous work has been hampered by sample size and illness spectrum limits. We sought to describe the pattern of MR-proADM in a broad CAP cohort, confirm its prognostic role, and compare its performance to procalcitonin, a novel biomarker of infection. Methods: We conducted a multicenter prospective cohort study in 28 community and teaching EDs. Patients with a clinical and radiographic diagnosis of CAP were enrolled. We stratified MR-proADM levels a priori into quartiles and quantified severity of illness using the pneumonia severity index (PSI); and confusion (abbreviated mental test score of < 8), urea > 7 mmol/L, respiratory rate > 30 breaths/min, BP < 90 mm Hg systolic or < 60 mm Hg diastolic, age > 65 years (CURB-65). The primary outcome was 30-day mortality. Results: A total of 1,653 patients formed the study cohort. MR-proADM levels consistently rose with PSI class and 30-day mortality (p < 0.001). MR-proADM had a higher area under the curve for 30-day mortality than procalcitonin (0.76 vs 0.65, respectively; p < 0.001), but adding MR-proADM to the PSI in all subjects minimally improved performance. Among low-risk subjects (PSI classes I to III), mortality was low and did not differ by MR-proADM quartile. However, among high-risk subjects (PSI class IV/V; n ‫؍‬ 546), subjects in the highest MR-proADM quartile (n ‫؍‬ 232; 42%) had higher 30-day mortality than those in MR-proADM quartiles 1 to 3 (23% vs 9%, respectively; p < 0.0001). Similar results were seen with CURB-65. MR-proADM and procalcitonin levels were generally concordant; only 6% of PSI class IV/V subjects in the highest MR-proADM quartile had very low procalcitonin levels (< 0.1 ng/mL). Conclusions: In our multicenter CAP cohort, MR-proADM levels correlate with increasing severity of illness and death. High MR-proADM levels offer additional risk stratification in high-risk CAP patients, but otherwise MR-proADM levels do not alter PSI-based risk assessment in most CAP patients.(CHEST 2009; 136:823-831)

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Section: Psi Class IIIsupporting

confidence: 83%

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confidence: 99%

Midregional Proadrenomedullin as a Prognostic Tool in Community-Acquired Pneumonia

Huang

Angus

Kellum

et al. 2009

Chest

125

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“…Conceptually, this seeming dichotomy probably represents a ''fire versus firefighter'' epiphenomenon, where the proportional presence of firefighters at a fire reflects their protective, rather than causative, role [40]. Therefore, elevated pro-adrenomedullin levels seen with increased illness severity and mortality might represent an endogenous, protective role for adrenomedullin [40], in an attempt to decrease inflammation, apoptosis and infection-induced organ damage [41,42]. Henceforth, higher proadrenomedullin levels would reflect greater inflammatory stimuli or more pronounced systemic repercussions of the disease, possibly explaining this biomarker's predictive properties in COPD and other respiratory conditions, such as pneumonia, sepsis and dyspnoea with and without heart failure [40,[43][44][45][46][47][48].…”

Section: Pro-adrenomedullin As An Alternative To the 6mwt For Mortalimentioning

confidence: 99%

Adrenomedullin refines mortality prediction by the BODE index in COPD: the “BODE-A” index

Stolz¹,

Κostikas²,

Blasi³

et al. 2013

Eur Respir J

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The BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index is wellvalidated for mortality prediction in chronic obstructive pulmonary disease (COPD). Concentrations of plasma pro-adrenomedullin, a surrogate for mature adrenomedullin, independently predicted 2-year mortality among inpatients with COPD exacerbation.We compared accuracy of initial pro-adrenomedullin level, BODE and BODE components, alone or combined, in predicting 1-year or 2-year all-cause mortality in a multicentre, multinational observational cohort with stable, moderate to very severe COPD.Pro-adrenomedullin was significantly associated (p,0.001) with 1-year mortality (4.7%) and 2-year mortality (7.8%) and comparably predictive to BODE regarding both (C statistics 0.691 versus 0.745 and 0.635 versus 0.679, respectively). Relative to using BODE alone, adding pro-adrenomedullin significantly improved 1-year and 2-year mortality prognostication (C statistics 0.750 and 0.818, respectively; both p,0.001). Pro-adrenomedullin plus BOD was more predictive than the original BODE including 6-min walk distance. In multivariable analysis, pro-adrenomedullin (likelihood ratio Chi-squared 13.0, p,0.001), body mass index (8.5, p50.004) and 6-min walk distance (7.5, p50.006) independently foretold 2-year survival, but modified Medical Research Council dyspnoea score (2.2, p50.14) and forced expiratory volume in 1 s % predicted (0.3, p50.60) did not.Pro-adrenomedullin plus BODE better predicts mortality in COPD patients than does BODE alone; proadrenomedullin may substitute for 6-min walk distance in BODE when 6-min walk testing is unavailable. @ERSpublications Pro-adrenomedullin improves BODE prediction of mortality in COPD patients and may substitute for 6-min walk distance http://ow.ly/qV5M3This article has supplementary material available from www.erj.ersjournals.com Clinical trial: This study is registered at www.controlled-trials.com with identifier number ISRCTN99586989.

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“…Other studies have further demonstrated that adrenomedulin, a peptide structurally related to CGRP, can act via both CGRP and adrenomedulin receptors to mediate its effects. Adrenomedulin has also been implicated in ROS generation (Yoshimoto et al 1998;Dakhama et al 2004;Rahman et al 2006;Itoh et al 2007;Kim et al 2010). Furthermore, CGRP has been found to play an important role in protecting myocytes, kidney cells, pancreatic B cells, and liver cells from the potentially damaging effects of ROS (She et al 2003;Kroeger et al 2009;Song et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Calcitonin Gene-Related Peptide Ameliorates Hyperoxia-Induced Lung Injury in Neonatal Rats

Dang

Yang

Wang

et al. 2012

Tohoku J. Exp. Med.

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Therapies with prolonged exposure to high-concentration oxygen are common in the treatment of critical pulmonary and cardiac conditions in newborns. However, prolonged exposure to hyperoxia could result in lung damages and developmental disorders manifested as acute lung injury and bronchopulmonary dysplasia, respectively. Calcitonin gene-related peptide (CGRP) has been shown to have a broad regulatory effect on the respiratory system. In this study, we explored the protective effects of CGRP on the hyperoxia-induced lung damage. Newborn Sprague-Dawley rats were randomly divided into three groups: normoxia, hyperoxia, and hyperoxia with CGRP. Hyperoxia groups were exposed to 95% oxygen for 14 days and treated once every other day with saline or CGRP. Hyperoxia exposure reduced the survival rate to 73%, when compared with the 93% survival rate observed in the normoxia group. The survival rate was improved to 84% with CGRP treatment. Treatment with CGRP under hyperoxia significantly alleviated the hyperoxia-induced lung histomorphological changes and the increases in leukocyte counts and total protein levels in bronchoalveolar lavage fluid that reflect the pulmonary microvasular damages. CGRP treatment also restored the decreased activity of superoxide dismutase, while it decreased the increased level of malondialdehyde in the lung tissues. Importantly, CGRP treatment significantly decreased the magnitude of the hyperoxia-mediated increase in the expression levels of tumor necrosis factor-α mRNA and transforming growth factor-β 1 protein. In conclusion, the hyperoxia-induced acute lung injury is associated with both oxidative stress and inflammatory responses, and CGRP may ameliorate the hyperoxia-induced lung injury by down-regulating these processes.

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Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats

Cited by 67 publications

References 55 publications

Midregional Proadrenomedullin as a Prognostic Tool in Community-Acquired Pneumonia

Midregional Proadrenomedullin as a Prognostic Tool in Community-Acquired Pneumonia

Adrenomedullin refines mortality prediction by the BODE index in COPD: the “BODE-A” index

Calcitonin Gene-Related Peptide Ameliorates Hyperoxia-Induced Lung Injury in Neonatal Rats

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