The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton Victoria 3168, Australia.
Cardiovasc Pathol. 2012 Sep-Oct;21(5):428-35. doi: 10.1016/j.carpath.2011.12.003. Epub 2012 Jan 28.
Elevated plasma C-reactive protein (CRP) is a biomarker of cardiovascular diseases (CVDs), but its potential roles as a participant of the disease process are not well defined. Although early endothelial cell injury and dysfunction are recognized events in CVD, the initiating events are not well established. Here we investigated the local myocardial CRP levels and cardiac microvessel densities in control and CVD tissue samples. Using in vitro methodologies, we investigated the direct effects of CRP on human endothelial cells.
Cardiac specimens were collected at autopsy within 4 h of death and were classified as normal controls or documented evidence of CVD. The regional prevalence of CRP and the cardiac microvessels (<40 μm) were investigated using immunohistochemistry. For in vitro experiments, human umbilical vein endothelial cells were incubated with CRP. Intracellular oxidant levels were assessed using 2',7'-dichlorofluorescein diacetate fluorescence microscopy, and cell survival was concurrently determined. Effects of chemical antioxidants on endothelial cell survival were also tested.
Myocardial CRP levels were elevated in CVD specimens. This was associated with reduced cardiac microvessels, and this rarefaction was inversely correlated to adjacent myocardial CRP prevalence. CRP caused concentration-dependent increases in oxidant production and cell apoptosis.
These findings provide evidence supporting myocardial CRP as a locally produced inflammatory marker and as a potential participant in endothelial toxicity and microvascular rarefaction.
血浆 C 反应蛋白（CRP）升高是心血管疾病（CVD）的生物标志物，但它作为疾病过程参与者的潜在作用尚未明确界定。尽管早期内皮细胞损伤和功能障碍是 CVD 的公认事件，但起始事件尚不清楚。在这里，我们研究了对照和 CVD 组织样本中的局部心肌 CRP 水平和心脏微血管密度。我们使用体外方法学研究了 CRP 对人内皮细胞的直接影响。
在死亡后 4 小时内通过尸检收集心脏标本，并将其分类为正常对照或有 CVD 证据的组织。使用免疫组织化学法研究 CRP 的区域性流行情况和心脏微血管（<40 μm）。对于体外实验，将人脐静脉内皮细胞与 CRP 孵育。使用 2'，7'-二氯荧光素二乙酸酯荧光显微镜评估细胞内氧化剂水平，并同时确定细胞存活率。还测试了化学抗氧化剂对内皮细胞存活的影响。
CVD 标本中的心肌 CRP 水平升高。这与心脏微血管减少有关，这种稀疏与相邻心肌 CRP 流行呈负相关。CRP 导致氧化剂产生和细胞凋亡的浓度依赖性增加。
这些发现提供了证据，支持心肌 CRP 作为局部产生的炎症标志物，以及作为内皮毒性和微血管稀疏的潜在参与者。
