Circulating products of C-type natriuretic peptide and links with organ function in health and disease

Prickett, Timothy C. R.; Espiner, Eric A.

doi:10.1016/j.peptides.2020.170363

Cited by 25 publications

(24 citation statements)

References 192 publications

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“…Increased circulating VEGFA may point to an underlying strain to the cardiovascular system (53) in individuals with co-incident high levels of platelet activation. Correlation with other proteins of cardiovascular health, including NPPC (54,55) and FABP9 (56), further support this hypothesis. Finally, among the highly correlated proteins was PCSK9 that has a central role not only in LDL metabolism (57-59) but has been shown to promote platelet activation (60) and can be found elevated in sepsis (61).…”

Section: Discussionmentioning

confidence: 79%

Signaling through FcγRIIA and the C5a-C5aR pathway mediates platelet hyperactivation in COVID-19

Apostolidis

Sarkar

Giannini

et al. 2021

Preprint

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Patients with COVID-19 present with a wide variety of clinical manifestations. Thromboembolic events constitute a significant cause of morbidity and mortality in patients infected with SARS-CoV-2. Severe COVID-19 has been associated with hyperinflammation and pre-existing cardiovascular disease. Platelets are important mediators and sensors of inflammation and are directly affected by cardiovascular stressors. In this report, we found that platelets from severely ill, hospitalized COVID-19 patients exhibit higher basal levels of activation measured by P-selectin surface expression, and have a poor functional reserve upon in vitro stimulation. Correlating clinical features to the ability of plasma from COVID-19 patients to stimulate control platelets identified ferritin as a pivotal clinical marker associated with platelet hyperactivation. The COVID-19 plasma-mediated effect on control platelets was highest for patients that subsequently developed inpatient thrombotic events. Proteomic analysis of plasma from COVID-19 patients identified key mediators of inflammation and cardiovascular disease that positively correlated with in vitro platelet activation. Mechanistically, blocking the signaling of the FcγRIIa-Syk and C5a-C5aR pathways on platelets, using antibody-mediated neutralization, IgG depletion or the Syk inhibitor fostamatinib, reversed this hyperactivity driven by COVID-19 plasma and prevented platelet aggregation in endothelial microfluidic chamber conditions, thus identifying these potentially actionable pathways as central for platelet activation and/or vascular complications in COVID-19 patients. In conclusion, we reveal a key role of platelet-mediated immunothrombosis in COVID-19 and identify distinct, clinically relevant, targetable signaling pathways that mediate this effect. These studies have implications for the role of platelet hyperactivation in complications associated with SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 79%

Signaling through FcγRIIA and the C5a-C5aR pathway mediates platelet hyperactivation in COVID-19

Apostolidis

Sarkar

Giannini

et al. 2021

Preprint

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“…C-type natriuretic peptide (CNP) is a paracrine growth factor widely expressed across numerous tissues 1 with diverse functions including regulation of endochondral bone growth, blood flow and pressure in the microcirculation, anti-inflammatory actions, gamete maturation and neurogenesis and connectivity 2 . The best defined of these factors in humans is the crucial role of the hormone in skeletal growth in driving growth plate expansion.…”

Section: Introductionmentioning

confidence: 99%

Evidence of feedback regulation of C-type natriuretic peptide during Vosoritide therapy in Achondroplasia

Prickett

Espiner

Irving

et al. 2021

Sci Rep

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Evidence from genetic disorders of CNP signalling suggests that plasma concentrations of CNP are subject to feedback regulation. In subjects with Achondroplasia (Ach), CNP intracellular activity is suppressed and plasma concentrations are raised but the therapeutic impact of exogenous CNP agonists on endogenous CNP is unknown. In this exploratory dose finding and extension study of 28 Ach children receiving Vosoritide over a 5 year period of treatment, endogenous CNP production was assessed using measurements of plasma aminoterminal proCNP (NTproCNP) adjusted for age and sex and normalised as standard deviation score (SDS), and then related to skeletal growth. Before treatment NTproCNP SDS was raised. Within the first 3 months of accelerating growth, levels were significantly reduced. Across the 5 years of sustained growth, levels varied widely and were markedly increased in some subjects during adolescence. Plasma NTproCNP was suppressed at 4 h post-injection in proportion to the prevailing level of hormone resistance as reflected by SDS before injection. We conclude CNP remains subject to regulation during growth promoting doses of Vosoritide. Fall in CNP during accelerating growth is consistent with an indirect feedback whereas the fall at 4 h is likely to be a direct effect from removal of intra cellular CNP resistance.

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“…Among them, there are mentioned growth hormone, thyroid hormones, oestrogens and androgens as well as insulin-like growth factors (IGFs), fibroblast growth factors (FGFs), the indian hedgehog homolog (IHH), parathyroid hormone-related peptide (PTHrP), bone morphogenetic proteins (BMPs), signal molecules belonging to the WNT protein family, vascular endothelial growth factor (VEGF), as well as C-type natriuretic peptide (CNP) [1,2,3,4]. CNP is one of the human natriuretic peptides with a relatively weak (in physiological concentration) diuretic action [1,5]. The gene encoding human CNP, named as NPPC (natriuretic peptide precursor C), contains two exons and is located on chromosome 2 (2q37.1) (http://www.genecards.org).…”

Section: Introduction and Objectivementioning

confidence: 99%

“…The gene encoding human CNP, named as NPPC (natriuretic peptide precursor C), contains two exons and is located on chromosome 2 (2q37.1) (http://www.genecards.org). Its relatively high level of expression has been detected (among others) in proliferating and pre-hypertrophic chondrocytes of the growth cartilage of the long bones, spine vertebrae, and facial bones [5,6]. The product of the NPPC gene is the 126-amino acid CNP prepropeptide (preproCNP), from which the 103-amino acid CNP propeptide (pro-CNP) is produced with the participation of the serine protease.…”

Section: Introduction and Objectivementioning

confidence: 99%

C-type natriuretic peptide and its contribution to bone growth

Kulik-Rechberger¹,

Trojanowska-Szostek²

2021

Ann Agric Environ Med.

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Circulating products of C-type natriuretic peptide and links with organ function in health and disease

Cited by 25 publications

References 192 publications

Signaling through FcγRIIA and the C5a-C5aR pathway mediates platelet hyperactivation in COVID-19

Signaling through FcγRIIA and the C5a-C5aR pathway mediates platelet hyperactivation in COVID-19

Evidence of feedback regulation of C-type natriuretic peptide during Vosoritide therapy in Achondroplasia

C-type natriuretic peptide and its contribution to bone growth

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