Cardiac Safety Biomarkers for Preclinical Cardiotoxicity Testing

Biomarkers have a longstanding role as indicators of biological changes. In drug development they serve dual purposes: predicting drug efficacy and identifying potential drug toxicity. Cardiotoxicity in one of the causes why preclinical safety tests fail during drug development. Therefore, monitoring cardiac toxicity with biomarkers is an essential part during drug development.

Cardiac Safety Biomarkers for Preclinical Cardiotoxicity Testing

The cardiac biomarkers NT-proANP and NT-proBNP

The biomarkers NT-proANP and NT-proBNP are cardiac hormones released in response to the stretching of the heart muscle . They belong to the group of natriuretic peptides and serve as cardiac biomarkers in both human and preclinical settings (1-4).

Biomedica offers reliable ELISA kits for measuring NT-proBNP and NT-proANP in both human and rodent samples.

Example of a Biomedica ELISA kit

 

Rat NT-proBNP ELISA – NEW

• Product code: BI-1204R
• Sample type: rat serum, plasma
• Sample volume: 10 µL/well
• Sensitivity: LOD 21 pg/ml
• Standard curve range: 0 – 3,200 pg/ml
• Specificity: Endogenous (natural) and recombinant human NT-proBNP (1-76)
• Assay time: 3.5 hours
• Reference value information for rat samples is provided. Instructions for use
• Citation click here (5)

 

also available: NT-proBNP ELISA (cat.no. SK-1204) – for human serum and plasma samples

• CE marked for IVD use in the EU
• Proficiency testing , saliva protocol
• Widely cited

 

NT-proANP ELISA

• Product code: BI-20892
• Sample types: Serum, plasma, urine, cell culture supernatant (human, rat, mouse, rabbit samples)

Due to the high sequence homology of NT-proANP among species the assay has been used not only in human samples but also in rodent (rat, mouse) rabbit, dog samples

• Sample volume: 10 µL/well
• Sensitivity: LOD 0.05 nmol/l (= 0.64 ng/ml)
• Standard curve range: 0 – 10 nmol/l (= 0 – 127 ng/ml)
• Specificity: endogenous (natural) and recombinant human NT-proANP (equivalent to proANP 1-98)
• There is high cross-reactivity between animal species.
• Assay time: 3.5 hours
• Citations all , citations with use of rat/mouse samples
• Instructions for use 

 

 

NT-proANP – a marker of drug-induced hypertrophy in rats

The validity of NT-proANP measurements as a tool for the detection of cardiovascular disorders in rats was demonstrated in an interlaboratory comparative study using Biomedica’s NT-proANP ELISA assay (Cat. No. BI-20892). Rat samples were analyzed and evaluated among 5 different laboratories by the PSTC-CHWG (Predictive Safety Testing Consortium and Cardiac Hypertrophy Working Group). The results demonstrated that the Biomedica NT-proANP ELISA assay (#BI-20892) is robust and technically adequate for the detection of serum NT-proANP levels in SD rats (6, 7).

 

Literature

1. Atrial and brain natriuretic peptides: Hormones secreted from the heart. Nakagawa Y, Nishikimi T, Kuwahara K. Peptides. 2019 Jan;111:18-25. doi: 10.1016/j.peptides.2018.05.012. Epub 2018 May 31. PMID: 29859763.
2. Cardiac natriuretic peptides. Goetze JP, Bruneau BG, Ramos HR, Ogawa T, de Bold MK, de Bold AJ. Nat Rev Cardiol. 2020 Nov;17(11):698-717. doi: 10.1038/s41569-020-0381-0. Epub 2020 May 22. PMID: 32444692.
3. Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy . Dunn, M.E., Manfredi, T.G., Agostinucci, K.,  Engle, S.K., Powe J., King, N.M.P., Rodriguez, L.A, Gropp, K.E., Gallacher, M., Vetter, F.J.,  More, V., Shimpi, P.,  Serra, D., Colton, H.M., for The Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium . 2017. Toxicol Pathol 45(2): 334-352. PMID: 27102652
4. Natriuretic Peptides as Cardiovascular Safety Biomarkers in Rats: Comparison With Blood Pressure, Heart Rate, and Heart Weight . Engle, S.K., and Watson, D.E.  2016. Toxicol Sci 149: 458 – 472. PMID: 26609138.
5. Leucine Supplementation Improves Diastolic Function in HFpEF by HDAC4 Inhibition. Alves PKN, Schauer A, Augstein A, Männel A, Barthel P, Joachim D, Friedrich J, Prieto ME, Moriscot AS, Linke A, Adams V Cells. 2023 Nov 2;12(21):2561. doi: 10.3390/cells12212561. PMID: 37947639; PMCID: PMC10648219.
6. Cross-laboratory analytical validation of the cardiac biomarker NT-proANP in rat. Vinken P, Reagan WJ, Rodriguez LA, Buck WR, Lai-Zhang J, Goeminne N, Barbacci G, Liu R, King NM, Engle SK, Colton H.J Pharmacol Toxicol Methods. 2016; 77:58-65. doi: 10.1016/j.vascn.2015.10.002. PMID: 26516096.
7. Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium. Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy. Dunn ME et al., Toxicol Pathol. 2017; 45(2):344-352.