cGMP Signaling and Modulation in Heart Failure.
J Cardiovasc Pharmacol
; 75(5): 385-398, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-31464774
ABSTRACT
Cyclic GMP (cGMP) represents a classic intracellular second messenger molecule. Over the past 2 decades, important discoveries have identified that cGMP signaling becomes deranged in heart failure (HF) and that cGMP and its main kinase effector, protein kinase G, generally oppose the biological abnormalities contributing to HF, in experimental studies. These findings have influenced the design of clinical trials of cGMP-augmenting drugs in HF patients. At present, the trial results of cGMP-augmenting therapies in HF remain mixed. As detailed in this review, strong evidence now exists that protein kinase G opposes pathologic cardiac remodeling through regulation of diverse biological processes and myocardial substrates. Potential reasons for the failures of cGMP-augmenting drugs in HF may be related to biological mechanisms opposing cGMP or because of certain features of clinical trials, all of which are discussed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistemas do Segundo Mensageiro
/
GMP Cíclico
/
Insuficiência Cardíaca
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Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article