Research update
Adrenomedullin and the microvasculature

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Abstract

The peptide adrenomedullin shows a remarkable range of effects on the vasculature that include vasodilatation, regulation of vascular smooth muscle cell proliferation, inhibition of endothelial apoptosis and promotion of angiogenesis. It is becoming clear that either activation or disruption of adrenomedullin signalling might contribute to many pathologies including cardiovascular disease, pulmonary hypertension, atherosclerosis, renal failure, neoplastic growth, inflammatory disease and disorders of the reproductive tract. Recent advances in this area are reviewed.

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

References (30)

  • L.L. Nikitenko

    Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus

    Mol. Hum. Reprod.

    (2001)
  • T. Shindo

    Hypotension and resistance to lipopolysaccharide-induced shock in transgenic mice overexpressing adrenomedullin in their vasculature

    Circulation

    (2000)
  • T. Shindo

    Vascular abnormalities and elevated blood pressure in mice lacking adrenomedullin gene

    Circulation

    (2001)
  • P.D. Upton

    Adrenomedullin expression and growth inhibitory effects in distinct pulmonary artery smooth muscle cell subpopulations

    Am. J. Respir. Cell Mol. Biol.

    (2001)
  • L.L. Nikitenko

    Adrenomedullin is an autocrine regulator of endothelial growth in human endometrium

    Mol. Hum. Reprod.

    (2000)
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