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REVIEW article

Front. Endocrinol.
Sec. Cellular Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1461642
This article is part of the Research Topic Cyclic Nucleotide Phosphodiesterases (PDEs) Signaling in the Endocrine System View all 4 articles

Rethinking of phosphodiesterase 5 inhibition: the old, the new and the perspective in human health

Provisionally accepted
Clara Crescioli Clara Crescioli *Maria Paola Paronetto Maria Paola Paronetto
  • Dept. of Health Sciences, Foro Italico University of Rome, Rome, Italy

The final, formatted version of the article will be published soon.

    The phosphodiesterases type 5 (PDE5) are catalytic enzymes converting the second messenger cyclic guanosine monophosphate (cGMP) to 5' GMP. While intracellular cGMP reduction is associated with several detrimental effects, cGMP stabilization associates with numerous benefits. The PDE5 specific inhibitors, PDE5i, found their explosive fortune as first-line treatment for erectile dysfunction (ED), due to their powerful vasoactive properties. The favorable effect for ED emerged as side-effect when PDE5i were originally proposed for coronary artery disease (CAD). From that point on, the use of PDE5i captured the attention of researchers, clinicians, and companies. Indeed, PDE5-induced intracellular cGMP stabilization offers a range of therapeutic opportunities associated not only with vasoactive effects, but also with immune regulatory/anti-inflammatory actions. Chronic inflammation is acknowledged as the common link underlying most non-communicable diseases, including metabolic and cardiac diseases, autoimmune and neurodegenerative disorders, cancer. In this scenario, the clinical exploitation of PDE5i is undeniably beyond ED, representing a potential therapeutic tool in several human diseases. This review aims to overview the biological actions exerted by PDE5i, focusing on their ability as modulators of inflammation-related human diseases, with particular attention to inflammatory-related disorders, like cardiac diseases and cancer.

    Keywords: PDE5i, cGMP, Inflammation, cardiac diseases, Cancer

    Received: 08 Jul 2024; Accepted: 28 Aug 2024.

    Copyright: © 2024 Crescioli and Paronetto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Clara Crescioli, Dept. of Health Sciences, Foro Italico University of Rome, Rome, 00135, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.