Abstract
C-type natriuretic peptide (CNP) is an autocrine and paracrine mediator released by endothelial cells, cardiomyocytes and fibroblasts that regulates vital physiological functions in the cardiovascular system. These roles are conveyed via two cognate receptors, natriuretic peptide receptor B (NPR-B) and natriuretic peptide receptor C (NPR-C), which activate different signalling pathways that mediate complementary yet distinct cellular responses. Traditionally, CNP has been deemed the endothelial component of the natriuretic peptide system, while its sibling peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are considered the endocrine guardians of cardiac function and blood volume. However, accumulating evidence indicates that CNP not only modulates vascular tone and blood pressure, but also governs a wide range of cardiovascular effects including the control of inflammation, angiogenesis, smooth muscle and endothelial cell proliferation, atherosclerosis, cardiomyocyte contractility, hypertrophy, fibrosis, and cardiac electrophysiology. This review will focus on the novel physiological functions ascribed to CNP, the receptors/signalling mechanisms involved in mediating its cardioprotective effects, and the development of therapeutics targeting CNP signalling pathways in different disease pathologies.
Highlights
The natriuretic peptides are a family of three structurally related hormones that play unique and distinctive roles within the cardiovascular system
Contrary to this research is a study showing that the infusion of musclin lowers blood pressure in mice, an effect that is absent in natriuretic peptide receptor A (NPR-A) KO animals, suggesting that an increase in circulating levels of atrial natriuretic peptide (ANP) and/or brain natriuretic peptide (BNP) due to the blockade of peptide clearance by natriuretic peptide receptor C (NPR-C) accounts for this response [88]
This is further supported by data demonstrating that NPR-C agonism in spontaneously hypertensive rats (SHR) attenuates the development of high blood pressure, an effect that is not observed in control Wistar-Kyoto rats [89]
Summary
The natriuretic peptides are a family of three structurally related hormones that play unique and distinctive roles within the cardiovascular system. Most of the stimuli that are known to increase gene expression and/or trigger the release of CNP are pertinent to cardiovascular health including shear stress [24,25], inflammatory cytokines such as tumour necrosis factor (TNF)-α [26], interleukin (IL)1β [26,27], transforming growth factor (TGF)-β [12,28], and bacterial lipopolysaccharide [26,29] In accordance with these findings are studies showing that plasma levels of CNP are elevated in patients with heart failure (HF) [30] and sepsis [31]. CNP release is attenuated by oxidised low-density lipoprotein [32] and vascular endothelial growth factor [33]
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