Work

B-type natriuretic peptide is upregulated by c-Jun N-terminal kinase and contributes to septic hypotension

Year: 2020

Type: article

Abstract: B-type natriuretic peptide (BNP) is secreted by ventricular cardiomyocytes in response to various types of cardiac stress and has been used as a heart failure marker. In septic patients, increased BNP suggests poor prognosis; however, no causal link has been established. Among various effects, BNP decreases systemic vascular resistance and increases natriuresis that leads to lower blood pressure. We previously observed that JNK inhibition corrects cardiac dysfunction and suppresses cardiac BNP mRNA in endotoxemia. In this study, we investigated the transcriptional mechanism that regulates BNP expression and the involvement of plasma BNP in causing septic hypotension. Our in vitro and in vivo findings confirmed that activation of JNK signaling increases BNP expression in sepsis via direct binding of c-Jun in activating protein-1 (AP-1) regulatory elements of the Nppb promoter. Accordingly, genetic ablation of BNP, as well as treatment with a potentially novel neutralizing anti-BNP monoclonal antibody (19B3) or suppression of its expression via administration of JNK inhibitor SP600125 improved cardiac output, stabilized blood pressure, and improved survival in mice with polymicrobial sepsis. Therefore, inhibition of JNK signaling or BNP in sepsis appears to stabilize blood pressure and improve survival.

Source: JCI Insight

DOI: 10.1172/jci.insight.133675

Authors: Matthew Hoffman, Ioannis D. Kyriazis, Alexandra Dimitriou, Santosh K. Mishra, Walter J. Koch, Konstantinos Drosatos

Institutions: Temple University, North Carolina State University

Language: English

Topic: Sepsis Diagnosis and Treatment

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,100