Overview

Heart failure is a condition in which the cells of the heart weaken such that the heart can no longer pump enough blood to meet the demands of the body. Although treatments have been successful in prolonging survival, 30% of those inflected still succumb to the disease (Loh et al.). For some, effective treatment calls for a personalized medicine approach, in which biomarkers would be used to monitor disease progression and treatment in a noninvasive manner.

Natriuretic Peptides

Natriuretic peptides have been touted as useful biomarkers for the purpose of personalized heart failure treatments. Natriuretic peptides are a family of peptides which are structurally similar and are produced in the heart tissue in response to stimuli such as myocyte stretch. They function in the induction of natriuresis, (the excretion of large amounts of sodium in the urine), and as a result they are involved in maintaining heart pressure and volume, as well as regulating cardiovascular remodeling pathways.

Natriuretic peptides are mainly cited as biomarkers of heart disease, however, recent findings have shown that these peptides can be indicators of a number of ailments including stroke, diabetes, obesity, and hyperthyroidism.

Atrial Natriuretic Peptide

Atrial natriuretic peptide (ANP) was first discovered as a result of experimental injection of atrial tissue extract into rats. The injections led to natriuresis and a subsequent decrease in blood pressure. ANP was subsequently isolated and characterized.

ANP and Brain Natriuretic Peptide (discussed below) induce natriuresis via binding to guanylyl cyclase-coupled natriuretic peptide receptor type A. This binding starts a signaling pathway that results in not only natriuresis, but diuresis, vasodilation, and downregulation of the renin-angiotensin-aldosterone system.

Brain Natriuretic Peptide

Brain Natriuretic Peptide (BNP) is the gold standard of natriuretic peptide biomarkers. Like ANP, BNP is secreted by cardiomyocytes, and it is produced in response to mechanical myocyte stretch, which reflects increase in pressure and volume of the heart. BNP is a product of the processing of a longer peptide encoded by the NPPB gene, whose regulation in the atrial and ventricular tissue determines the amount of BNP that is synthesized and secreted. NPPB initially encodes a 134 aa prepropeptide that is cleaved into a 108 aa precursor peptide called proBNP108, as the result of the removal of a 26 aa signal peptide. proBNP108 is subsequently cleaved into 2 fragments, a biologically active, 32 aa, C-terminal peptide called BNP, and a biologically inert, 67 aa, N-terminal peptide, NT-proBNP.

BNP is synthesized in response to a number of stimuli including myocyte stretch (an indicator of heart failure), and cardiovascular tissue hypoxia. In addition, obesity is characterized by low levels of natriuretic peptides, while hyperthyroidism is characterized by an increase in BNP and NT-proBNP.

C-type Natriuretic Peptide

C-type natriuretic peptides (CNP) are produced in a number of human tissues, having prominence in vascular endothelial cells and the brain. Although CNP is structurally similar to ANP and BNP, it does not induce natriuresis. It binds to a separate receptor called guanylyl cyclase-coupled natriuretic peptide receptor type B, and has venodilatory and coronary vasodilatory effects. C-type peptide has also been found to prevent cardiac and vascular remodeling after cardiac tissue injury.

GenScript supports cadiovascular research and provides natriuretic peptide products and custom peptide synthesis to advance heart research.

References

Bach T et al. Identification of small molecule NPR-B antagonists by high throughput screening-potential use in heart failure. (2013) Naunyn Schmiedebergs Arch Pharmacol. 387: 5-14.

Loh JC. et al. Temporal Trends in Treatment and Outcomes for Advanced Heart Failure With Reduced Ejection Fraction From 1993–2010 Findings From a University Referral Center. (2013) Circ Heart Fail 6: 411-419.

Motiwala SR and Januzzi Jr JL. The Role of Natriuretic Peptides as Biomarkers for Guiding the Management of Chronic Heart Failure. (2013) Clinical Pharmacology & Therapeutics 93: 57-67.

Sellitti DF. Et al. Regulation of C-type natriuretic peptide expression. (2011) Peptides 32:1964–1971.

More Than Just Biomarkers

Natriuretic peptides can also be useful in developing heart disease treatments. Click below to see how one group used natriuretic peptides synthesized by GenScript in their work to screen a library of 20,000 small compounds to find BNP receptor antagonist drug candidates.

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