A Contemporary View of Natriuretic Peptides in the SARS-CoV-2 Era

Abstract

The heart releases natriuretic peptides (NPs) which represent an important hormonal axis with cardiorenal protective effects. In view of their properties, NPs have pathophysiologic, diagnostic and prognostic implications in several cardiovascular diseases (CVDs). Severe pulmonary inflammation, as induced by the SARS-COV2, may increase pulmonary pressure with potential influence on NPs release, whereby normal cardiovascular integrity becomes impaired. Moreover, pre-existing CVDs are strong negative prognostic factors since they exacerbate the effects of the viral infection and lead to worse outcomes. In this context, it may be expected that NPs exert a key protective role toward the virus infection whereas an impairment of NPs release contributes to the virus deleterious effects. In this review article we explore the potential involvement of NPs in the COVID-19 disease. To this aim, we will first focus on the interactions between NPs and the Ang II/ATIR arm of the renin-angiotensin-aldosterone system (RAAS) as well as with the protective ACE2/Ang (1-7) arm of the RAAS. Subsequently, we will review evidence that strongly supports the role of increased NT-proBNP level as a marker of cardiac damage and of worse prognosis in the COVID-19 affected patients. Finally, we will discuss the potential therapeutic benefits of these protective hormones toward the viral infection through their endothelial protective function, anti-inflammatory and anti-thrombotic effects. In conclusion, the potential implications of NPs in the SARS-CoV-2 infection, as discussed in our article, represent an important issue that deserves to be fully investigated.

Natriuretic Peptides: It Is Time for Guided Therapeutic Strategies Based on Their Molecular Mechanisms

“…NPs also inhibit the pathway of RAC1 (Ras-related C3 botulinum toxin substrate)/p38/MAPK (mitogen activated protein kinase), which is involved in the activation of Akt and mTOR and its downstream target p 70 S6K, the Ras/MEK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) signaling. These biological pathways lead to an increased expression of c-fos mRNA, JNK (c-JUN N-terminal kinase), and c-Src, which stimulate JAK2 (Janus kinase 2)-STAT3 (signal transducer and activator of transcription 3) through PKC (protein kinase C) and PyK2 (proline-rich tyrosine kinase 2) [ 47 , 48 , 49 ] ( Figure 2 ).…”

Hypertension and COVID-19: Current Evidence and Perspectives

“…In such a context, also angiotensin receptor/neprilysin inhibitors (ARNi), combining the blockade of AT1R and the ability to increase natriuretic peptide levels, which regulate cellular growth and proliferation, preserving endothelial function and integrity as well as vascular tone, might represent a potential therapeutic tool in the treatment of COVID-19 [ 78 ].…”

Peptide-Based Strategies Against SARS-CoV-2 Attack: An Updated In Silico Perspective

“…For instance, the antioxidant and anti-inflammatory effects of grehlin, have been considered to reduce the complications of the SARS-CoV-2 (Jafari et al, 2021). As well, since cardiovascular diseases are strong negative prognostic factors since they exacerbate the effects of the viral infection and lead to worse outcomes, it has been suggested that natriuretic peptides could exert a key protective role toward the virus infection whereas an impairment of NPs release contributes to the virus deleterious effects (Rubattu et al, 2021).…”