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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Evaluation of potential novel biomarkers for feline hypertrophic cardiomyopathy
Andrew Chong1, Jessica Joshua2, Shari Raheb1
1Department of Clinical Studies, Ontario Veterinary College, University of Guelph, 28 College Ave W, Guelph, Ontario N1G 2W1, Canada.
Insights
New biomarkers like insulin-like growth factor binding protein 2 (IGFBP-2) and WNT Family Member 5A (WNT5A) show promise for diagnosing feline hypertrophic cardiomyopathy (HCM) and its stages.
Area of Science:
- Veterinary Cardiology
- Biomarker Discovery
- Feline Medicine
Background:
- Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiac disease in cats.
- Current diagnostic methods, including echocardiography and existing biomarkers (NT-proBNP, cTnI), have limitations.
- Previous research identified differential expression of myocardial genes (IL-18, IGFBP-2, PYGB, WNT5A) in feline HCM.
Purpose of the Study:
- To investigate serum concentrations of IL-18, IGFBP-2, PYGB, and WNT5A RNA and protein in healthy cats, cats with subclinical HCM, and cats with HCM and congestive heart failure (CHF).
- To assess the potential of these biomarkers for diagnosing and staging feline HCM.
Main Methods:
- Serum samples were collected from three groups: healthy controls (n=8), subclinical HCM (n=8), and HCM + CHF (n=6).
- Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to measure serum RNA concentrations.
- Enzyme-linked immunosorbent assay (ELISA) was employed to determine serum protein levels.
Main Results:
- Serum IGFBP-2 RNA concentrations differed significantly among groups, being highest in cats with subclinical HCM.
- Serum IL-18 and WNT5A gene expression were significantly elevated in cats with HCM + CHF compared to healthy controls.
- WNT5A gene expression was also higher in cats with subclinical HCM compared to healthy controls; PYGB showed no significant differences.
Conclusions:
- Serum IGFBP-2, WNT5A, and IL-18 show potential as circulating biomarkers for feline HCM diagnosis and staging.
- Further large-scale clinical studies are warranted to validate these findings.
- These biomarkers may offer a less invasive and more accessible diagnostic approach compared to current methods.
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.
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