C-reactive protein (CRP) is an acute inflammatory protein detected in obese patients with metabolic syndrome. Moreover, increased CRP levels have been linked with atherosclerotic disease, congestive heart failure, and ischemic heart disease, suggesting that it is not only a biomarker but also plays an active role in the pathophysiology of cardiovascular diseases. Since endothelial dysfunction plays an essential role in various cardiovascular pathologies and is characterized by increased expression of cell adhesion molecules and inflammatory markers, we aimed to detect specific markers of endothelial dysfunction, inflammation, and oxidative stress in spontaneously hypertensive rats (SHR) expressing human CRP. This model is genetically predisposed to the development of the metabolic syndrome. Transgenic SHR male rats (SHR-CRP) and non-transgenic SHR (SHR) at the age of 8 months were used. Metabolic profile (including serum and tissue triglyceride (TAG), serum insulin concentrations, insulin-stimulated incorporation of glucose, and serum non-esterified fatty acids (NEFA) levels) was measured. In addition, human serum CRP, MCP-1 (monocyte chemoattractant protein-1), and adiponectin were evaluated by means of ELISA, histological analysis was used to study morphological changes in the aorta, and western blot analysis of aortic tissue was performed to detect expression of endothelial, inflammatory, and oxidative stress markers. The presence of human CRP was associated with significantly decreased insulin-stimulated glycogenesis in skeletal muscle, increased muscle and hepatic accumulation of TAG and decreased plasmatic cGMP concentrations, reduced adiponectin levels, and increased monocyte chemoattractant protein-1 (MCP-1) levels in the blood, suggesting pro-inflammatory and presence of multiple features of metabolic syndrome in SHR-CRP animals. Histological analysis of aortic sections did not reveal any visible morphological changes in animals from both SHR and SHR-CRP rats. Western blot analysis of the expression of proteins related to the proper function of endothelium demonstrated significant differences in the expression of p-eNOS/eNOS in the aorta, although endoglin (ENG) protein expression remained unaffected. In addition, the presence of human CRP in SHR in this study did not affect the expression of inflammatory markers, namely p-NFkB, P-selectin, and COX2 in the aorta. On the other hand, biomarkers related to oxidative stress, such as HO-1 and SOD3, were significantly changed, indicating the induction of oxidative stress. Our findings demonstrate that CRP alone cannot fully induce the expression of endothelial dysfunction biomarkers, suggesting other risk factors of cardiovascular disorders are necessary to be involved to induce endothelial dysfunction with CRP.

中文翻译：

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转基因人 C 反应蛋白影响自发性高血压大鼠主动脉的氧化应激，但不影响炎症生物标志物

C反应蛋白（CRP）是一种在患有代谢综合征的肥胖患者中检测到的急性炎症蛋白。此外，CRP水平升高与动脉粥样硬化性疾病、充血性心力衰竭和缺血性心脏病有关，表明它不仅是一种生物标志物，而且在心血管疾病的病理生理学中发挥着积极作用。由于内皮功能障碍在各种心血管病理中起着重要作用，其特征是细胞粘附分子和炎症标记物表达增加，因此我们旨在检测表达人 CRP 的自发性高血压大鼠 (SHR) 的内皮功能障碍、炎症和氧化应激的特异性标记物。该模型在遗传上容易发生代谢综合征。使用8个月龄的转基因SHR雄性大鼠(SHR-CRP)和非转基因SHR(SHR)。测量代谢特征（包括血清和组织甘油三酯（TAG）、血清胰岛素浓度、胰岛素刺激的葡萄糖掺入和血清非酯化脂肪酸（NEFA）水平）。此外，通过ELISA评估人血清CRP、MCP-1（单核细胞趋化蛋白-1）和脂联素，通过组织学分析研究主动脉的形态变化，并对主动脉组织进行蛋白质印迹分析以检测内皮、炎症和氧化应激标志物的表达。人 CRP 的存在与骨骼肌中胰岛素刺激的糖生成显着减少、肌肉和肝脏 TAG 积累增加、血浆 cGMP 浓度降低、脂联素水平降低以及单核细胞趋化蛋白 1 (MCP-1) 水平增加相关。血液，表明 SHR-CRP 动物具有促炎性和代谢综合征的多种特征。主动脉切片的组织学分析未显示 SHR 和 SHR-CRP 大鼠的动物有任何明显的形态学变化。与内皮正常功能相关的蛋白质表达的蛋白质印迹分析表明，主动脉中 p-eNOS/eNOS 的表达存在显着差异，但内皮糖蛋白 (ENG) 蛋白质表达不受影响。此外，本研究中SHR中人CRP的存在并不影响主动脉中炎症标志物，即p-NFkB、P-选择素和COX2的表达。另一方面，与氧化应激相关的生物标志物，如HO-1和SOD3，发生了显着变化，表明氧化应激的诱导。我们的研究结果表明，单独的 CRP 不能完全诱导内皮功能障碍生物标志物的表达，这表明心血管疾病的其他危险因素必须参与 CRP 诱导内皮功能障碍。