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

软骨中间层蛋白 1(CILP1)是否可以作为犬粘液瘤二尖瓣退化程度的新型生物标志物?

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作者:Hyeon-Jin Kim, Jihyun Kim, Soomin Kim, Ha-Jung Kim

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.

Conclusions

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

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.

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