Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology

Alexandra Petraina, Cristian Nogales, Thomas Krahn, Hermann Mucke, Thomas F. Lüscher, Rodolphe Fischmeister, David A. Kass, John C. Burnett, Adrian J. Hobbs, Harald H.H.W. Schmidt

Research output: Contribution to journalReview articlepeer-review

Abstract

Mechanism-based therapy centred on the molecular understanding of disease-causing pathways in a given patient is still the exception rather than the rule in medicine, even in cardiology. However, recent successful drug developments centred around the second messenger cyclic guanosine-3′-5′-monophosphate (cGMP), which is regulating a number of cardiovascular disease modulating pathways, are about to provide novel targets for such a personalized cardiovascular therapy. Whether cGMP breakdown is inhibited or cGMP synthesis is stimulated via guanylyl cyclases or their upstream regulators in different cardiovascular disease phenotypes, the outcomes seem to be so far uniformly protective. Thus, a network of cGMP-modulating drugs has evolved that act in a mechanism-based, possibly causal manner in a number of cardiac conditions. What remains a challenge is the detection of cGMPopathy endotypes amongst cardiovascular disease phenotypes. Here, we review the growing clinical relevance of cGMP and provide a glimpse into the future on how drugs interfering with this pathway may change how we treat and diagnose cardiovascular diseases altogether.

Original languageEnglish (US)
Pages (from-to)2085-2102
Number of pages18
JournalCardiovascular research
Volume118
Issue number9
DOIs
StatePublished - May 1 2022

Keywords

  • Biomarkers
  • Cyclic GMP
  • Guanylate cyclase
  • Natriuretic peptides
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

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