A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections

Author:

Spoto Silvia1,Basili Stefania2ORCID,Cangemi Roberto2ORCID,Yuste José Ramón34ORCID,Lucena Felipe5ORCID,Romiti Giulio Francesco2ORCID,Raparelli Valeria2ORCID,Argemi Josepmaria5ORCID,D’Avanzo Giorgio1,Locorriere Luciana1,Masini Francesco1ORCID,Calarco Rodolfo1,Testorio Giulia1,Spiezia Serenella1,Ciccozzi Massimo6ORCID,Angeletti Silvia78

Affiliation:

1. Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy

2. Department of Translational and Precision Medicine, Sapienza University, Viale dell’Università, 30, 00185 Rome, Italy

3. Division of Infectious Diseases, Faculty of Medicine, Clinica Universidad de Navarra, University of Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain

4. Department of Internal Medicine, Faculty of Medicine, Clinica Universidad de Navarra, University of Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain

5. Departamento de Medicina Interna, Clinica Universidad de Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain

6. Unit of Medical Statistics and Molecular Epidemiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy

7. Unit of Laboratory, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy

8. Research Unit of Clinical Laboratory Science, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy

Abstract

Adrenomedullin (ADM) is a peptide hormone produced primarily in the adrenal glands, playing a crucial role in various physiological processes. As well as improving vascular integrity and decreasing vascular permeability, ADM acts as a vasodilator, positive inotrope, diuretic, natriuretic and bronchodilator, antagonizing angiotensin II by inhibiting aldosterone secretion. ADM also has antihypertrophic, anti-apoptotic, antifibrotic, antioxidant, angiogenic and immunoregulatory effects and antimicrobial properties. ADM expression is upregulated by hypoxia, inflammation-inducing cytokines, viral or bacterial substances, strength of shear stress, and leakage of blood vessels. These pathological conditions are established during systemic inflammation that can result from infections, surgery, trauma/accidents or burns. The ability to rapidly identify infections and the prognostic, predictive power makes it a valuable tool in severe viral and bacterial infections burdened by high incidence and mortality. This review sheds light on the pathophysiological processes that in severe viral or bacterial infections cause endothelitis up to the development of organ damage, the resulting increase in ADM levels dosed through its more stable peptide mid-regional proadrenomedullin (MR-proADM), the most significant studies that attest to its diagnostic and prognostic accuracy in highlighting the severity of viral or bacterial infections and appropriate therapeutic insights.

Funder

Ministry of Education, Universities and Research

National Recovery and Resilience Plan

Next Generation EU

Publisher

MDPI AG

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