PHYMEDEXP, Université de Montpellier, INSERM, CNRS, Montpellier, France.
Laboratoire de Biochimie et d'hormonologie, CHU Lapeyronie, Montpellier, France.
Mol Cell Biochem. 2024 Jan;479(1):29-39. doi: 10.1007/s11010-023-04710-6. Epub 2023 Mar 28.
Cardiac alteration due to chronic kidney disease is described by tissue fibrosis. This remodeling involves myofibroblasts of various origins, including epithelial or endothelial to mesenchymal transitions. In addition, obesity and insulin resistance together or separately seem to exacerbate cardiovascular risk in chronic kidney disease (CKD). The main objective of this study was to assess if pre-existing metabolic disease exacerbates CKD-induced cardiac alterations. In addition, we hypothesised that endothelial to mesenchymal transition participates in this enhancement of cardiac fibrosis. Rats fed cafeteria type diet for 6 months underwent a subtotal nephrectomy at 4 months. Cardiac fibrosis was evaluated by histology and qRT-PCR. Collagens and macrophages were quantified by immunohistochemistry. Endothelial to mesenchymal transitions were assessed by qRT-PCR (CD31, VE-cadherin, α-SMA, nestin) and also by CD31 immunofluorescence staining. Rats fed with cafeteria type regimen were obese, hypertensive and insulin resistant. Cardiac fibrosis was predominant in CKD rats and was highly majored by cafeteria regimen. Collagen-1 and nestin expressions were higher in CKD rats, independently of regimen. Interestingly, in rats with CKD and cafeteria diet we found an increase of CD31 and α-SMA co-staining with suggest an implication of endothelial to mesenchymal transition during heart fibrosis. We showed that rats already obese and insulin resistant had an enhanced cardiac alteration to a subsequent renal injury. Cardiac fibrosis process could be supported by a involvement of the endothelial to mesenchymal transition phenomenon.
慢性肾脏病引起的心脏改变由组织纤维化描述。这种重塑涉及到各种来源的肌成纤维细胞，包括上皮或内皮向间充质的转变。此外，肥胖和胰岛素抵抗一起或单独似乎会加重慢性肾脏病（CKD）的心血管风险。本研究的主要目的是评估是否存在预先存在的代谢疾病会加重 CKD 引起的心脏改变。此外，我们假设内皮向间充质转化参与了这种心脏纤维化的增强。6 个月的 cafeteria 饮食喂养的大鼠在 4 个月时接受部分肾切除术。通过组织学和 qRT-PCR 评估心脏纤维化。通过免疫组织化学定量胶原蛋白和巨噬细胞。通过 qRT-PCR（CD31、VE-cadherin、α-SMA、巢蛋白）和 CD31 免疫荧光染色评估内皮向间充质转化。喂食 cafeteria 饮食的大鼠肥胖、高血压和胰岛素抵抗。CKD 大鼠的心脏纤维化为主， cafeteria 饮食更为严重。CKD 大鼠的胶原-1 和巢蛋白表达更高，与饮食无关。有趣的是，在 CKD 和 cafeteria 饮食的大鼠中，我们发现 CD31 和 α-SMA 的共染色增加，提示内皮向间充质转化在心脏纤维化过程中的作用。我们表明，已经肥胖和胰岛素抵抗的大鼠在随后的肾脏损伤中，心脏改变更为明显。心脏纤维化过程可能与内皮向间充质转化现象有关。
