A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections
Silvia Spoto,
Stefania Basili,
Roberto Cangemi,
José Ramón Yuste,
Felipe Lucena,
Giulio Francesco Romiti,
Valeria Raparelli,
Josepmaria Argemi,
Giorgio D’Avanzo,
Luciana Locorriere,
Francesco Masini,
Rodolfo Calarco,
Giulia Testorio,
Serenella Spiezia,
Massimo Ciccozzi,
Silvia Angeletti
Affiliations
Silvia Spoto
Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy
Stefania Basili
Department of Translational and Precision Medicine, Sapienza University, Viale dell’Università, 30, 00185 Rome, Italy
Roberto Cangemi
Department of Translational and Precision Medicine, Sapienza University, Viale dell’Università, 30, 00185 Rome, Italy
José Ramón Yuste
Division of Infectious Diseases, Faculty of Medicine, Clinica Universidad de Navarra, University of Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain
Felipe Lucena
Departamento de Medicina Interna, Clinica Universidad de Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain
Giulio Francesco Romiti
Department of Translational and Precision Medicine, Sapienza University, Viale dell’Università, 30, 00185 Rome, Italy
Valeria Raparelli
Department of Translational and Precision Medicine, Sapienza University, Viale dell’Università, 30, 00185 Rome, Italy
Josepmaria Argemi
Departamento de Medicina Interna, Clinica Universidad de Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain
Giorgio D’Avanzo
Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy
Luciana Locorriere
Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy
Francesco Masini
Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy
Rodolfo Calarco
Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy
Giulia Testorio
Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy
Serenella Spiezia
Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy
Massimo Ciccozzi
Unit of Medical Statistics and Molecular Epidemiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
Silvia Angeletti
Unit of Laboratory, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy
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.