Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy

Abstract

Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor γ agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.

Myocardial Injury and Overload among Amateur Marathoners as Indicated by Changes in Concentrations of Cardiovascular Biomarkers

“…NT-proANP is a biologically inactive fragment (98 amino acids) of ANP prohormone and has been reported as a useful diagnostic and prognostic tool for patients with heart failure and myocardial infarction. In a recent experimental study, it was shown that NT-proANP was excellent for indicating cardiac hypertrophy [26].…”

Comparison of ANP and BNP Granular Density in Atria of Rats After Physiological and Pathological Hypertrophy

“…Recent evidence has provided information on the translational utility of these biomarkers in the drug development space, where they have promise for the identification of compounds with potential cardiac liabilities. 1,2…”

“…In summary, serum natriuretic peptides serve as differential translational biomarkers between drug- and exercise-induced pathological and physiological cardiac hypertrophy. 1 Furthermore, the utility of two-faced immunolabeling of atria and ventricle ANP and BNP can identify population differences in natriuretic peptides to highlight differences between physiological and pathological cardiac stress.…”

Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories

“…Recently, a cross-laboratory comparison study presented results demonstrating the ELISA assay detection of serum NT-proANP in rats to be technically adequate with acceptable intra- and inter-assay and inter-laboratory precision and accuracy (Vinken et al , 2016). There have been reports of several successful uses of NT-proANP and NT-proBNP to detect cardiotoxicity in preclinical settings (Dunn et al , 2016, Stokes et al , 2015, Colton et al , 2011, Casartelli et al , 2011). …”