关键词: CA125 Epicardium Heart failure MUC16

Mesh : Humans Pericardium / pathology metabolism Male Middle Aged Inflammation / pathology Female Aged Biomarkers / metabolism blood CA-125 Antigen / blood metabolism Fibrosis Adipose Tissue / metabolism pathology Adipogenesis Epicardial Adipose Tissue

来  源:   DOI:10.1186/s12967-024-05351-z   PDF(Pubmed)

Abstract:
BACKGROUND: Carbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis.
METHODS: Epicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively.
RESULTS: The median age was 71 (63-74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels.
CONCLUSIONS: Epicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis).
摘要:
背景:碳水化合物抗原125(CA125)是MUC-16的蛋白水解片段,在心力衰竭(HF)中增加并与炎症相关,流体过载,和更严重的不良事件。我们的主要目的是研究CA125在心外膜的表达及其与炎症的关系。脂肪生成,和纤维化。
方法:从接受心脏直视手术的151例非选择患者中获取心外膜脂肪活检和血液。免疫组织化学,ELISA,或实时PCR用于分析CA125和炎症细胞标志物的蛋白质或mRNA表达水平,成纤维细胞,和脂肪细胞。分离并培养来自心外膜的上皮或基质细胞,以鉴定CA125及其与脂肪生成和纤维化途径的关联。分别。
结果:中位年龄为71(63-74)岁,106例(70%)为男性,62例(41%)在手术前已明确诊断为HF.与CA125M11抗体孵育后,心外膜脂肪活检切片在上皮层上确定阳性和比色染色,提供了CA125在人心外膜中表达的第一个描述。心外膜CA125与心外膜脂肪组织中的炎症和纤维化标志物呈强且正相关,而与脂肪生成途径标志物呈负相关。在调整了潜在的混杂因素(例如先前的HF诊断和血浆CA125水平)后,这种关系仍然很重要。
结论:心外膜细胞表达CA125,其与心外膜脂肪组织中的炎症和成纤维细胞标志物呈正相关。这些结果表明CA125可能在生物学上参与HF进展(从脂肪生成到纤维化的转变)。
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