Effect of intermedin/adrenomedullin2 on the pulmonary vascular bed in hypoxia-induced pulmonary hypertensive rats

Telli, Gökçen; Tel, Banu Cahide; Yersal, Nilgün; Korkusuz, Petek; Gümüşel, Bülent

doi:10.1016/j.lfs.2017.11.031

Cited by 13 publications

(6 citation statements)

References 29 publications

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“…Interestingly, patent ductus arteriosus (PDA) is a serious congenital heart disease that can lead to irreversible pulmonary hypertension 33 . We confirm here the down-regulation of apelin and show, for the first time, the down-regulation of adrenomedullin by BMP9, two known critical actors that can impair pulmonary endothelial function 34,35 .…”

Section: Discussionsupporting

confidence: 83%

Selective BMP-9 Inhibition Partially Protects Against Experimental Pulmonary Hypertension

Desroches-Castan

Mallet

et al. 2019

Circulation Research

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Rationale: Although many familial cases of pulmonary arterial hypertension (PAH) exhibit an autosomal dominant mode of inheritance with the majority having mutations in essential constituents of the bone morphogenetic protein (BMP) signaling, the specific contribution of the long-term loss of signal transduction triggered by the type 2 BMP receptor (BMPR2) remains poorly characterized. Objective: To investigate the role of BMP9, the main ligand of ALK1/BMPR2 heterocomplexes, in pulmonary hypertension (PH). Method and Results: The absence of BMP9 in Bmp9-/-mice and its inhibition in C57BL/6 mice using neutralizing anti-BMP9 antibodies substantially prevent against chronic hypoxia induced PH judged by right ventricular systolic pressure (RVSP) measurement, right ventricular hypertrophy, and pulmonary distal arterial muscularization. In agreement with these observations, we found that the BMP9/BMP10 ligand trap ALK1ECD administered in monocrotaline (MCT) or Sugen/hypoxia (SuHx) rats substantially attenuate proliferation of pulmonary vascular cells, inflammatory cell infiltration and regresses established PH in rats. Our data obtained in human pulmonary endothelial cells derived from controls and PAH patients indicate that BMP9 can affect the balance between endothelin-1, apelin and adrenomedullin. We reproduced these in vitro observations in mice chronically exposed to hypoxia, with Bmp9-/-mice exhibiting lower mRNA levels of the vasoconstrictor peptide endothelin (ET)-1 and higher levels of the two potent vasodilator factors apelin and adrenomedullin (ADM) compared with Bmp9 +/+ littermates. Conclusion: Taken together, our data indicate that the loss of BMP9, by deletion or inhibition, has beneficial effects against PH onset and progression.

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Section: Discussionsupporting

confidence: 83%

Selective BMP-9 Inhibition Partially Protects Against Experimental Pulmonary Hypertension

Desroches-Castan

Mallet

et al. 2019

Circulation Research

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“…In chronic hypoxiainduced PH ADM2/IMD provided potent vasodilation in pulmonary arteries of rats and intraarterial administration was reduced the perfusion pressure of hypoxic lungs. This reduction indicates the possible application of ADM2/IMD administration in the human with PH 119,120 .…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 94%

The Cardiopulmonary Effects of Calcitonin-Gene Related Peptide Family

Telli¹,

Tel²,

Gümüşel³

2019

tjps

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The cardiopulmonary diseases are very common in the population. They are high-cost diseases and there are still no definitive treatments. The roles of members of the calcitonin-gene-related peptide (CGRP) family in the cardiopulmonary diseases have been studied for many years and promising results are obtained. Especially in recent years, two important members of the family, adrenomedullin and adrenomedullin2/intermedin, are considered as new treatment targets in cardiopulmonary diseases. In this review, the roles of CGRP family peptides in cardiopulmonary diseases has been investigated according to the studies that were performed to the present day.

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“…Peptides have the advantage of being stable, having a low molecular weight and high lipophilicity (9). In recent years, the area of peptidomics has rapidly developed, and the association between numerous polypeptides have been investigated with the occurrence and prevention of obesity and its related complications (50,51). Therefore, identifying novel polypeptide drugs, which could prevent and cure obesity would improve the regulatory network of adipocyte function and offer new possibilities for the treatment of obesity.…”

Section: Classical Polypeptides In Obesitymentioning

confidence: 99%

“…peptide, which serves a significant role in protecting the cardiovascular system (50,89). AM2 treatment has been demonstrated to significantly reduce blood glucose levels, improve glucose tolerance and insulin sensitivity by inhibiting major histocompatibility complex (MHC) II in adipocytes (90).…”

Section: Adrenomedullin-2 (Am2) Am2/intermediate Is a Secretedmentioning

confidence: 99%

Research and prospect of peptides for use in obesity treatment (Review)

et al. 2020

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Obesity and its related diseases, such as type 2 diabetes, hypertension and cardiovascular disease, are steadily increasing worldwide. Over the past few decades, numerous studies have focused on the differentiation and function of brown and beige fat, providing evidence for their therapeutic potential in treating obesity. However, no specific novel drug has been developed to treat obesity in this way. Peptides are a class of chemically active substances, which are linked together by amino acids using peptide bonds. They have specific physiological activities, including browning of white fat. As signal molecules regulated by the neuroendocrine system, the role of polypeptides, such as neuropeptide Y, brain-gut peptide and glucagon-like peptide in obesity and its related complications has been revealed. Notably, with the rapid development of peptidomics, peptide drugs have been widely used in the prevention and treatment of metabolic diseases, due to their short half-life, small apparent distribution volume, low toxicity and low side effects. The present review summarizes the progress and the new trend of peptide research, which may provide novel targets for the prevention and treatment of obesity.

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Effect of intermedin/adrenomedullin2 on the pulmonary vascular bed in hypoxia-induced pulmonary hypertensive rats

Cited by 13 publications

References 29 publications

Selective BMP-9 Inhibition Partially Protects Against Experimental Pulmonary Hypertension

Selective BMP-9 Inhibition Partially Protects Against Experimental Pulmonary Hypertension

The Cardiopulmonary Effects of Calcitonin-Gene Related Peptide Family

Research and prospect of peptides for use in obesity treatment (Review)

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