Adrenomedullin Signaling in Cardiovascular and Metabolic Disorders

Adrenomedullin is a multifunctional peptide hormone expressed by endothelial cells, smooth muscle cells and various tissues. Signalling through the calcitonin receptor-like receptor in complex with receptor activity-modifying proteins (RAMPs), it triggers cyclic AMP production, activation of endothelial nitric oxide synthase and engagement of the AMP-activated protein kinase (AMPK) pathway. These cascades support vasodilatation, regulation of vascular permeability, anti-inflammatory and antifibrotic effects alongside natriuresis and diuresis. In cardiovascular disorders such as hypertension, heart failure and cardiogenic shock, dysregulation of adrenomedullin signalling contributes to vascular remodelling, endothelial dysfunction and impaired haemodynamics. Metabolic disorders including obesity-related hypertension exhibit attenuated adrenomedullin sensitivity, exacerbating inflammatory stress and arterial stiffness. Clinically, circulating mid-regional proadrenomedullin (MR-proADM) serves as a prognostic biomarker of organ dysfunction and mortality. Emerging therapies aim to harness adrenomedullin’s protective actions via peptide analogues, receptor modulators and targeted antibodies. Understanding the interplay with the renin–angiotensin–aldosterone system and endothelial junction proteins has global significance for risk stratification and the development of novel interventions across diverse patient populations.

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Adrenomedullin Signaling in Cardiovascular and Metabolic Disorders publication trend

The graph below shows the total number of articles in adrenomedullin signaling in cardiovascular and metabolic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Adrenomedullin (ADM): A 52-amino-acid peptide hormone involved in vasodilatation and vascular homeostasis.

Receptor activity-modifying proteins (RAMPs): Single-transmembrane proteins that, in association with the calcitonin receptor-like receptor, determine adrenomedullin receptor specificity.

Mid-regional proadrenomedullin (MR-proADM): A stable fragment of the adrenomedullin precursor used as a circulating biomarker.

AMP-activated protein kinase (AMPK): A serine/threonine kinase that regulates cellular energy balance and mediates many of adrenomedullin’s vascular effects.

Vascular endothelial (VE)-cadherin: An adherens junction protein critical for endothelial barrier integrity.

References

1. Adrenomedullin Improves Hypertension and Vascular Remodeling partly through the Receptor-Mediated AMPK Pathway in Rats with Obesity-Related Hypertension. International Journal of Molecular Sciences (2023).
2. Regulation and Dysregulation of Endothelial Permeability during Systemic Inflammation. Cells (2022).
3. Adrenomedullin: a marker of impaired hemodynamics, organ dysfunction, and poor prognosis in cardiogenic shock. Annals of Intensive Care (2017).