Intermedin (Adrenomedullin-2): a Potential Protective Role in Human Aortic Endothelial Cells

Pearson, Lachlan; Yandle, Timothy G.; Nicholls, M. Gary; Evans, John J.

doi:10.1159/000204098

Cited by 18 publications

(23 citation statements)

References 45 publications

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“…IMD treatment increased the activity of NO synthase (NOS) and content of NO in tissues and augmented the uptake of L-arginine by cells [29]. NO activates GC and elevates intracellular cGMP levels for multiple effects such as vasodilation, anti-oxidative stress, and inhibition of cell apoptosis [8,30,31]. IMD153 significantly increased NO production and endothelial NOS (eNOS) activity in rat aortas and was more potent than equivalent ADM [32].…”

Section: Distribution and Production Of Imdmentioning

confidence: 99%

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Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease

Zhang

Tang

et al. 2014

Sci. China Life Sci.

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Intermedin (IMD) or adrenomedullin 2 is a novel peptide related to the calcitonin gene-related peptide (CGRP) family. Via calcitonin receptor-like receptor/receptor activity modifying proteins, the common receptor complexes of CGRP, IMD exerts a wide range of biological effects, especially regulation of cardiovascular homeostasis. Proteolytic processing of a larger IMD precursor yields a series of biologically active C-terminal fragments, IMD1-53, IMD1-47 and IMD8-47. IMD and its receptors are present in the cardiovascular system, and IMD is present at low levels in plasma. In the cardiovascular system, IMD has multiple functions such as regulation of blood pressure and cardiac function, pro-angiogenesis, endothelial barrier function protection, anti-oxidative stress, and anti-endoplasmic reticulum stress. IMD participates widely in the pathogenesis of atherosclerosis, hypertension, pulmonary arterial hypertension and vascular calcification. It is a vascular regulatory factor of homeostasis and a vital endogenous protective factor against vascular diseases. intermedin, vessel, homeostasis, vascular diseases Citation:Ni XQ, Zhang JS, Tang CS, Qi YF. Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease. Sci China Life Sci, 2014, 57: 781 -789,

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Section: Distribution and Production Of Imdmentioning

confidence: 99%

“…Moreover, Rac1 activity is regulated by the RhoA/Rock pathway in RCECs but not HUVECs. Human aortic endothelial cells were found to express IMD mRNA and secreted IMD peptide [8]. IMD mRNA expression depended on metabolic conditions and was selectively regulated in a contrary fashion to ADM mRNA.…”

Section: Imd and Atherosclerosismentioning

confidence: 99%

Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease

Zhang

Tang

et al. 2014

Sci. China Life Sci.

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“…Furthermore, AM2 stimulated cell migration and tube formation via extracellular signal related kinase (ERK) activation in cultured endothelial cells and increased capillary/ arteriole density in an ischaemic hindlimb model (Smith et al 2009). AM2 also displays anti-apoptotic properties (Pearson et al 2009, Song et al 2009. Interestingly, AM2 is also upregulated under hypoxic conditions in mouse lung, hepatocytes and endothelial cells at least in part via HIF-1a (Copple et al 2009, Pfeil et al 2009.…”

Section: Am2 (Intermedin) and Cancermentioning

confidence: 99%

Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: opportunities and challenges

Hay

Walker²,

Poyner³

2010

Endocrine Related Cancer

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Adrenomedullin (AM), adrenomedullin 2 (AM2/intermedin) and calcitonin gene-related peptide (CGRP) are members of the calcitonin family of peptides. They can act as growth or survival factors for a number of tumours, including those that are endocrine-related. One mechanism through which this occurs is stimulating angiogenesis and lymphangiogenesis. AM is expressed by numerous tumour types and for some cancers, plasma AM levels can be correlated with the severity of the disease. In cancer models, lowering AM content or blocking AM receptors can reduce tumour mass. AM receptors are complexes formed between a seven transmembrane protein, calcitonin receptor-like receptor and one of the two accessory proteins, receptor activity-modifying proteins (RAMPs) 2 or 3 to give the AM 1 and AM 2 receptors respectively. AM also has affinity at the CGRP receptor, which uses RAMP1. Unfortunately, due to a lack of selective pharmacological tools or antibodies to distinguish AM and CGRP receptors, the precise receptors and signal transduction pathways used by the peptides are often uncertain. Two other membrane proteins, RDC1 and L1/G10D (the 'ADMR'), are not currently considered to be genuine CGRP or AM receptors. In order to properly evaluate whether AM or CGRP receptor inhibition has a role in cancer therapy, it is important to identify which receptors mediate the effects of these peptides. To effectively distinguish AM 1 and AM 2 receptors, selective receptor antagonists need to be developed. The development of specific CGRP receptor antagonists suggests that this is now feasible.

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“…IMD has been quantified in plasma of rat and human (3), but the origin of the peptide in plasma is unclear. The pituitary is likely to make a significant contribution but, recently, human aortic endothelial cells (ECs) were also shown to express IMD mRNA and secrete the peptide (6).…”

Section: And Colleagues (1) Discovered the Human Form Of This Peptidementioning

confidence: 99%

Involvement of vascular endothelial growth factor signaling in CLR/RAMP1 and CLR/RAMP2-mediated pro-angiogenic effect of intermedin on human vascular endothelial cells

Albertin

Sorato²,

Oselladore³

et al. 2010

Int J Mol Med

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Abstract. Intermedin (IMD) is a recently discovered peptide closely related to adrenomedullin. Its principal physiological activity is its role in the regulation of the cardiovascular system, where it exerts a potent hypotensive effect. In addition, data were recently provided showing that this peptide is able to exert a clearcut pro-angiogenic effect both in vitro and in vivo. IMD acts through the non-selective interaction with receptor complexes formed by the dimerization of calcitoninlike receptor (CLR) with the receptor activity-modifying proteins RAMP1, 2 or 3. Thus, in the present study, the role of CLR/RAMP complexes in mediating the pro-angiogenic effect induced by IMD on human umbilical vein endothelial cells (HUVECs) cultured on Matrigel was examined. Real-time PCR demonstrated the expression of IMD, CLR/RAMP1 and CLR/RAMP2 (but not CLR/RAMP3) mRNA in HUVECs. IMD exerted a significant in vitro angiogenic action, specifically triggered by the binding of the peptide to CLR/RAMP complexes. Both CLR/RAMP1 and CLR/RAMP2 appeared to mediate the pro-angiogenic effect, which was associated with a significant increase of vascular endothelial growth factor (VEGF) mRNA expression 18 h following IMD administration, indicating that the observed pro-angiogenic effects are related, at least in part, to an increased synthesis of this growth factor promoted by the peptide. Western blot analysis, however, showed a significant increase of VEGF receptor-2 phosphorylation as early as 5 min following IMD administration, indicating that IMD induces a pro-angiogenic response in human vascular endothelial cells not only via CLR/RAMP-induced release of VEGF, but also during signal initiation and propagation by transactivating the VEGF receptor-2 machinery.

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Intermedin (Adrenomedullin-2): a Potential Protective Role in Human Aortic Endothelial Cells

Cited by 18 publications

References 45 publications

Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease

Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease

Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: opportunities and challenges

Involvement of vascular endothelial growth factor signaling in CLR/RAMP1 and CLR/RAMP2-mediated pro-angiogenic effect of intermedin on human vascular endothelial cells

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