Evaluation of potential novel biomarkers for feline hypertrophic cardiomyopathy

Res Vet Sci. 2024 Nov:180:105430. doi: 10.1016/j.rvsc.2024.105430. Epub 2024 Oct 9.

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy in cats. The diagnosis can be difficult, requiring advanced echocardiographic skills. Additionally, circulating biomarkers (N-terminal pro-B type natriuretic peptide and cardiac troponin I) have several limitations when used for HCM screening. In previous work, we identified interleukin 18 (IL-18), insulin-like growth factor binding protein 2 (IGFBP-2), brain-type glycogen phosphorylase B (PYGB), and WNT Family Member 5 A (WNT5A) as myocardial genes that show significant differential expression between cats with HCM and healthy cats. The products of these genes are released into the circulation, and we hypothesized that IL-18, IGFBP-2, PYGB, and WNT5A serum RNA and protein concentrations differ between healthy cats, cats with subclinical HCM, and those with HCM and congestive heart failure (HCM + CHF). Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) and enzyme-linked immunosorbent assay (ELISA) were applied to evaluate gene and protein expression, respectively, in the serum of eight healthy controls, eight cats with subclinical HCM, and six cats with HCM + CHF. Serum IGFBP-2 RNA concentrations were significantly different among groups and were highest in cats with subclinical HCM. Compared to healthy controls, serum IL-18 and WNT5A gene expression were significantly higher in cats with HCM + CHF, and WNT5A was higher in cats with subclinical HCM. No differences were observed for PYGB. These results indicate that further investigation via large scale clinical studies for IGFBP-2, WNT5A, and IL-18 may be valuable in diagnosing and staging feline HCM.

Keywords: Biomarkers; Congestive heart failure; Feline; Gene expression; Hypertrophic cardiomyopathy; Serum RNA.

MeSH terms

  • Animals
  • Biomarkers* / blood
  • Cardiomyopathy, Hypertrophic* / blood
  • Cardiomyopathy, Hypertrophic* / diagnosis
  • Cardiomyopathy, Hypertrophic* / genetics
  • Cardiomyopathy, Hypertrophic* / veterinary
  • Cat Diseases* / blood
  • Cat Diseases* / diagnosis
  • Cat Diseases* / genetics
  • Cats
  • Enzyme-Linked Immunosorbent Assay / veterinary
  • Female
  • Glycogen Phosphorylase / blood
  • Glycogen Phosphorylase / genetics
  • Insulin-Like Growth Factor Binding Protein 2 / blood
  • Insulin-Like Growth Factor Binding Protein 2 / genetics
  • Interleukin-18 / blood
  • Interleukin-18 / genetics
  • Male
  • Reverse Transcriptase Polymerase Chain Reaction / veterinary
  • Wnt Proteins / genetics
  • Wnt-5a Protein / blood
  • Wnt-5a Protein / genetics

Substances

  • Biomarkers
  • Wnt-5a Protein
  • Interleukin-18
  • Insulin-Like Growth Factor Binding Protein 2
  • Wnt Proteins
  • Glycogen Phosphorylase