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. 2023 Mar 7;19(1):59.
doi: 10.1186/s12917-023-03583-7.

Can cartilage intermediate layer protein 1 (CILP1) use as a novel biomarker for canine myxomatous mitral valve degeneration levels or not?

Hyeon-Jin Kim  1   2 , Jihyun Kim  1   2 , Soomin Kim  1   2 , Ha-Jung Kim  3   4
Affiliations

Can cartilage intermediate layer protein 1 (CILP1) use as a novel biomarker for canine myxomatous mitral valve degeneration levels or not?

Hyeon-Jin Kim et al. BMC Vet Res. .

Abstract

Background: Myxomatous mitral valve degeneration (MMVD) is the most common degenerative heart disease in dogs and is associated with irreversible changes in the valve tissue. Although traditional cardiac biomarkers are efficient for diagnosing MMVD, there are limitations, therefore, it is important to find novel biomarkers. Cartilage intermediate layer protein 1 (CILP1), an extracellular matrix-derived protein, acts as a transforming growth factor-β antagonist and is involved in myocardial fibrosis. This study aimed to evaluate serum CILP1 levels in canines with MMVD. Dogs with MMVD were staged according to the American College of Veterinary Internal Medicine consensus guidelines. Data analysis was performed using the Mann-Whitney U test, Spearman's correlation, and receiver operating characteristic (ROC) curves.

Results: CILP1 levels were elevated in dogs with MMVD (n = 27) compared to healthy controls (n = 8). Furthermore, results showed that CILP1 levels were significantly higher in stage C group dogs compared to healthy controls. The ROC curve of CILP1 and NT-proBNP were good predictors of MMVD, although no similarity was observed between the two. Left ventricular end-diastolic diameter normalized to the body weight (LVIDdn) and left atrial to aorta dimension (LA/Ao) showed a strong association with CILP1 levels; however, no correlation was observed between CILP1 levels and vertebral heart size (VHS) and vertebral left atrial score (VLAS). The optimal cut-off value was selected from the ROC curve and dogs were classified according to the cut-off value (1.068 ng/mL, sensitivity 51.9%, specificity 100%). Results showed a significant association of CILP1 with cardiac remodeling indicators, such as VHS, VLAS, LA/Ao, and LVIDdn.

Conclusions: CILP1 can be an indicator of cardiac remodeling in canines with MMVD and therefore, can be used as an MMVD biomarker.

Keywords: Biomarker; Cardiac; Cartilage intermediate layer protein 1; Dogs; Myxomatous mitral valve degeneration.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Boxplot of serum CILP1 and NT-proBNP levels in healthy controls and dogs with MMVD (a, b). Boxplot of serum CILP1 and NT-proBNP levels in healthy controls (n = 8) and dogs with MMVD staged according to the ACVIM consensus (c, d). Stage B1 (n = 4), stage B2 (n = 6), stage C (n = 15), and stage D (n = 2). The boxplot shows the average value along with the minimum and maximum values. *P < 0.05, **P < 0.01, and ***P < 0.001
Fig. 2
Fig. 2
Comparison of receiver operating characteristic (ROC) plots of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cartilage intermediate layer protein 1 (CILP1) for detecting MMVD in dogs
Fig. 3
Fig. 3
Correlation of CILP1 levels with VHS (a), VLAS (b), LA/Ao (c), and LVIDdn (d) in healthy controls and dogs with MMVD. Solid line represents a power trendline of the data. *P < 0.05, **P < 0.01, and ***P < 0.001
Fig. 4
Fig. 4
Box and scatter plots comparing VHS, VLAS, LA/Ao, and LVIDdn according to the CILP1 cut-off values in the MMVD group. Horizontal bars represent the mean value. *P < 0.05, **P < 0.01, and ***P < 0.001
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