Trends in Pharmacological Sciences
Research updateAdrenomedullin and the microvasculature
Section snippets
Vascular effects of adrenomedullin
Expression of adrenomedullin and its receptors by a variety of cell types, including ECs and VSMCs 2, 3, 4, 9, 10, defines the paracrine, autocrine and endocrine modes of adrenomedullin-mediated vascular effects 1, 7, 9, 10, 11, 12, 13, 14, 15, 16 (Fig. 1).
The paracrine action of adrenomedullin has implications in atherogenesis and neoplasia 3, 11 because it promotes crosstalk between ECs, VSMCs and fibroblasts, macrophages or tumour cells. Endothelial secretion of adrenomedullin is thought not
Molecular mechanisms of vascular responses to adrenomedullin
The mechanisms of adrenomedullin-mediated vasodilatation have been well described 2, 4; however, how the peptide elicits other effects in vascular and extra-vascular tissues is less well defined.
Adrenomedullin as a contributory peptide in microvascular dysfunction
Adrenomedullin appears to play a role in modulating blood pressure and vascular development, and hence organ function in cardiovascular, renal and pulmonary disease and in reproductive disorders 2, 3, 4, 7. Recent data on the structure and function of the peptide and its receptor system offer novel therapeutic strategies in the treatment of these pathologies.
The investigation of the stability of the genomic structure for the genes encoding adrenomedullin and CRLR has recently attracted
Concluding remarks
Adrenomedullin is clearly a more significant player in vascular function than previously thought. Disruption of the genomic structure or signal transduction pathways mediated through adrenomedullin receptor(s) by genetic and environmental factors might contribute to common disorders that affect the vasculature. A heterogeneous range of drugs (including gene delivery and biochemical and molecular approaches) should be considered for selective targeting of the specific mechanisms involved in
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Adrenomedullin: A potential therapeutic target for retinochoroidal disease
2016, Progress in Retinal and Eye ResearchCitation Excerpt :Another study in a diabetic animal model showed that inhibition of AM via NO signaling pathways prevented functional loss in the retina (Blom et al., 2011). AM also has pleiotropic effects including vasodilation, anti-inflammation, anti-apoptosis, and angiogenesis (Abe et al., 2003; Brain and Grant, 2004; Kato et al., 2005; Kitamura et al., 1993; Nikitenko et al., 2002; Ribatti et al., 2005). It is of note that AM is also known to act as an anti-inflammatory factor through suppression of inflammatory molecules such as TNF-α, IL-1β, and cyclooxygenase-2 in several disease models (Ashizuka et al., 2009; Gonzalez-Rey et al., 2006; Talero et al., 2011).
Adrenomedullin haploinsufficiency predisposes to secondary lymphedema
2013, Journal of Investigative DermatologyCitation Excerpt :Therefore, therapeutic strategies to prevent or treat lymphedema are limited (Rockson, 2008a; Tammela and Alitalo, 2010). Adrenomedullin (AM) is a 52-amino-acid vasoactive peptide (Kitamura et al., 1993a; Nikitenko et al., 2002; Brain and Grant, 2004). Together with proadrenomedullin N-terminal peptide (PAMP), AM is encoded by the ADM gene (adrenomedullin gene) (Kitamura et al., 1993b).
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