Evaluation of serum biomarkers of collagen turnover in cats with hypertrophic cardiomyopathy.

摘要

BACKGROUND Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM). Human patients with HCM have high serum concentrations of biomarkers of collagen synthesis, indicating a profibrotic state. This abnormality exists in sarcomere mutation carriers both with and without overt left ventricular hypertrophy, suggesting its potential use in early identification of HCM. Whether serum levels of biomarkers of collagen synthesis are increased in cats with HCM is unknown.;HYPOTHESIS: We hypothesized that serum biomarkers of collagen turnover could be measured in cats using commercially available enzyme-linked immunosorbent assays (ELISAs), that cats with HCM would have higher serum concentrations of a collagen synthesis biomarker than normal cats, and that a collagen degradation biomarker would not differ between cats with HCM and normal cats.;METHODS Cats presenting to a university veterinary cardiology referral service were prospectively evaluated and enrolled in the study when they had an echocardiographic diagnosis of HCM or no structural heart disease. Cats with a high serum thyroid hormone (T4) concentration, high systolic arterial blood pressure, recent or ongoing diuretic administration, echocardiographic diagnosis of cardiomyopathies other than HCM or of other congenital or acquired lesions, and/or overt signs of hypovolemia, were excluded. The diagnosis of HCM was based on echocardiographic measurements of the interventricular septum (IVS) and/or left ventricular free wall (LVFW) >5.5 mm in thickness. Cats with IVS and LVFW <5.5 mm and no other echocardiographic abnormalities were considered normal. Serum concentrations of C-terminal propeptide of type I procollagen (PICP, marker of collagen synthesis) were attempted to be evaluated using 2 commercially available ELISAs. One was previously validated for use in humans (MicrovueTM EIA kit; QuidelRTM) and one in rats [ELISA kit for procollagen type I C-terminal propeptide (PICP); Uscn Life Science Inc.] A commercially available ELISA previously validated for use in cats (Serum CrossLapsRTM ELISA; Nordic Bioscience Diagnostics) was used to quantify serum concentrations of C-terminal telopeptide of type I collagen (CTx) as a marker of collagen degradation. We compared serum [CTx] of cats with HCM and controls.;RESULTS Forty-seven cats qualified for and participated in the study: 28 with an echocardiographic diagnosis of HCM and 19 normal controls. Serum samples from 12 additional cats with unknown echocardiographic statuses were also used in assay evaluation. In 22 experiments (8 for PICP using 1 ELISA, 10 for PICP using a second ELISA, and 4 for CTx) conducted on a total of 114 blood samples from 59 cats and 4 rats, stability, precision and linearity testing failed to provide reliable results for quantifying serum [PICP] using either ELISA. There was no difference in serum [CTx] between cats with HCM and normal controls (HCM: mean 0.248 ng/ml; controls: mean 0.253 ng/ml; p=0.4).;CONCLUSIONS The 2 ELISAs evaluated are not valid for quantifying 'serum [PICP] in the cat; therefore, we are unable to conclude whether or not serum biomarkers reflect increased collagen synthesis in the pathophysiology of HCM in cats. There was no evidence of enhanced collagen degradation in cats with HCM compared to normal controls.