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评估猫肥厚型心肌病潜在的新型生物标志物。

Evaluation of potential novel biomarkers for feline hypertrophic cardiomyopathy.

机构信息

Department of Clinical Studies, Ontario Veterinary College, University of Guelph, 28 College Ave W, Guelph, Ontario N1G 2W1, Canada.

Department of Clinical Studies, Ontario Veterinary College, University of Guelph, 28 College Ave W, Guelph, Ontario N1G 2W1, Canada; Department of Pathobiology, Ontario Veterinary College, University of Guelph, 50 Stone Road E., Guelph, ON N1G 2W1, Canada.

出版信息

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

DOI:10.1016/j.rvsc.2024.105430
PMID:39395261
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.

摘要

肥厚型心肌病(HCM)是猫最常见的心肌病。诊断可能具有挑战性,需要先进的超声心动图技能。此外,循环生物标志物(N 端脑利钠肽前体和心肌肌钙蛋白 I)在用于 HCM 筛查时存在一些局限性。在之前的工作中,我们发现白细胞介素 18(IL-18)、胰岛素样生长因子结合蛋白 2(IGFBP-2)、脑型糖原磷酸化酶 B(PYGB)和 WNT 家族成员 5A(WNT5A)是 HCM 猫和健康猫之间存在显著差异表达的心肌基因。这些基因的产物会释放到循环中,我们假设 IL-18、IGFBP-2、PYGB 和 WNT5A 的血清 RNA 和蛋白浓度在健康猫、亚临床 HCM 猫和 HCM 伴充血性心力衰竭(HCM+CHF)猫之间存在差异。逆转录定量聚合酶链反应(RTqPCR)和酶联免疫吸附测定(ELISA)分别用于评估血清中基因和蛋白的表达,共 8 只健康对照、8 只亚临床 HCM 猫和 6 只 HCM+CHF 猫纳入研究。各组间血清 IGFBP-2 RNA 浓度存在显著差异,亚临床 HCM 猫的 IGFBP-2 RNA 浓度最高。与健康对照组相比,HCM+CHF 猫的血清 IL-18 和 WNT5A 基因表达显著升高,亚临床 HCM 猫的 WNT5A 基因表达更高。PYGB 无差异。这些结果表明,通过大规模临床研究进一步研究 IGFBP-2、WNT5A 和 IL-18 可能对诊断和分期猫的 HCM 具有重要价值。

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Clinical-Diagnostic and Therapeutic Advances in Feline Hypertrophic Cardiomyopathy.猫肥厚性心肌病的临床诊断与治疗进展
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