Adrenomedullin – Current perspective on a peptide hormone with significant therapeutic potential

Fischer, Jan‐Patrick; Els‐Heindl, Sylvia; Beck‐Sickinger, Annette G.

doi:10.1016/j.peptides.2020.170347

Cited by 27 publications

(34 citation statements)

References 162 publications

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Section: Discussionmentioning

confidence: 99%

“…Adrenomedullin (ADM) is a peptide hormone with important roles in the regulation of the cardiovascular and lymphatic systems [ 17 ]. ADM was revealed to be a potential biomarker and candidate for therapeutic interventions [ 17 ]. A study investigating tissue punches from dentate gyrus revealed ADM as an inhibitor of angiogenesis to be related to neuroinflammation in patients with MDD [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

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Neuropeptides as the Shared Genetic Crosstalks Linking Periodontitis and Major Depression Disorder

et al. 2021

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Background. The aim of this study was at investigating the association between major depressive disorder (MDD) and periodontitis based on crosstalk genes and neuropeptides. Methods. Datasets for periodontitis (GSE10334, GSE16134, and GSE23586) and MDD (GSE38206 and GSE39653) were downloaded from GEO. Following batch correction, a differential expression analysis was applied (MDD: ∣ log 2 FC ∣ > 0 and periodontitis ∣ log 2 FC ∣ ≥ 0.5 , p < 0.05 ). The neuropeptide data were downloaded from NeuroPep and NeuroPedia. Intersected genes were potential crosstalk genes. The correlation between neuropeptides and crosstalk genes in MDD and periodontitis was analyzed with Pearson correlation coefficient. Subsequently, regression analysis was performed to calculate the differentially regulated link. Cytoscape was used to map the pathways of crosstalk genes and neuropeptides and to construct the protein-protein interaction network. Lasso regression was applied to screen neuropeptides, whereby boxplots were created, and receiver operating curve (ROC) analysis was conducted. Results. The MDD dataset contained 30 case and 33 control samples, and the periodontitis dataset contained 430 case and 139 control samples. 35 crosstalk genes were obtained. A total of 102 neuropeptides were extracted from the database, which were not differentially expressed in MDD and periodontitis and had no intersection with crosstalk genes. Through lasso regression, 9 neuropeptides in MDD and 43 neuropeptides in periodontitis were obtained. Four intersected neuropeptide genes were obtained, i.e., ADM, IGF2, PDYN, and RETN. The results of ROC analysis showed that IGF2 was highly predictive in MDD and periodontitis. ADM was better than the other three genes in predicting MDD disease. A total of 13 crosstalk genes were differentially coexpressed with four neuropeptides, whereby FOSB was highly expressed in MDD and periodontitis. Conclusion. The neuropeptide genes ADM, IGF2, PDYN, and RETN were intersected between periodontitis and MDD, and FOSB was a crosstalk gene related to these neuropeptides on the transcriptomic level. These results are a basis for future research in the field, needing further validation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neuropeptides as the Shared Genetic Crosstalks Linking Periodontitis and Major Depression Disorder

et al. 2021

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“…CALCRL is also expressed in a host of other tissues and its role in adipose tissue remains to be established (42,43). PLIN1 is a lipid droplet surface protein almost exclusively expressed in adipocytes and has a wellestablished role in regulating both triglyceride and diacylglycerol hydrolysis (44).…”

Section: Discussionmentioning

confidence: 99%

Identification of rare loss of function variation regulating body fat distribution

Koprulu

Zhao

Wheeler

et al. 2021

Preprint

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Biological and translational insights from large-scale, array-based genetic studies of fat distribution, a key determinant of metabolic health, have been limited by the difficulty in linking identified predominantly non-coding variants to specific gene targets. Rare coding variant analyses provide greater confidence that a specific gene is involved, but do not necessarily indicate whether gain or loss of function would be of most therapeutic benefit. Here we use a dual approach that combines the power of genome-wide analysis of array-based rare, non-synonymous variants in 184,246 individuals of UK Biobank with exome-sequence-based rare loss of function gene burden testing. The data indicates that loss-of-function (LoF) of four genes (PLIN1, INSR, ACVR1C and PDE3B) is associated with a beneficial impact on WHRadjBMI and increased gluteofemoral fat mass, whereas PLIN4 LoF adversely affects these parameters. This study robustly implicates these genes in the regulation of fat distribution, providing new and in some cases somewhat counter-intuitive insight into the potential consequences of targeting these molecules therapeutically.

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“…CTR functions independently as a CT receptor, but the other receptors require the assistance of the RAMPs. For instance, CTR + RAMPs serve as the amylin receptor, CRLR + RAMP1 serves as the CGRP receptor, CRLR + RAMP2 serves as the AM1 receptor, and CRLR + RAMP3 serves as the AM2 receptor [ 26 ]. AM has equal affinity for both AM1 and AM2 receptors.…”

Section: Biosynthesis Of Am and Its Receptorsmentioning

confidence: 99%

“…AM has equal affinity for both AM1 and AM2 receptors. AM and AM2/intermedin exhibit a similar high affinity for AM2 receptor [ 26 ]. Models have shown that the knockout (KO) of AM is lethal at mid-gestation due to serious vascular abnormalities and causes extreme hydrops [ 27 , 28 ].…”

Section: Biosynthesis Of Am and Its Receptorsmentioning

confidence: 99%

Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases

Kita

Kïtamura

2022

Hypertens Res

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Adrenomedullin (AM) is a vasodilative peptide with various physiological functions, including the maintenance of vascular tone and endothelial barrier function. AM levels are markedly increased during severe inflammation, such as that associated with sepsis; thus, AM is expected to be a useful clinical marker and therapeutic agent for inflammation. However, as the increase in AM levels in cardiovascular diseases (CVDs) is relatively low compared to that in infectious diseases, the value of AM as a marker of CVDs seems to be less important. Limitations pertaining to the administrative route and short half-life of AM in the bloodstream (<30 min) restrict the therapeutic applications of AM for CVDs. In early human studies, various applications of AM for CVDs were attempted, including for heart failure, myocardial infarction, pulmonary hypertension, and peripheral artery disease; however, none achieved success. We have developed AM as a therapeutic agent for inflammatory bowel disease in which the vasodilatory effect of AM is minimized. A clinical trial evaluating this AM formulation for acute cerebral infarction is ongoing. We have also developed AM derivatives that exhibit a longer half-life and less vasodilative activity. These AM derivatives can be administered by subcutaneous injection at long-term intervals. Accordingly, these derivatives will reduce the inconvenience in use compared to that for native AM and expand the possible applications of AM for treating CVDs. In this review, we present the latest translational status of AM and its derivatives.

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Adrenomedullin – Current perspective on a peptide hormone with significant therapeutic potential

Cited by 27 publications

References 162 publications

Neuropeptides as the Shared Genetic Crosstalks Linking Periodontitis and Major Depression Disorder

Neuropeptides as the Shared Genetic Crosstalks Linking Periodontitis and Major Depression Disorder

Identification of rare loss of function variation regulating body fat distribution

Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases

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