Gross Marie-Luise, Meyer Hans-Peter, Ziebart Heike, Rieger Peter, Wenzel Uta, Amann Kerstin, Berger Irina, Adamczak Marcin, Schirmacher Peter, Ritz Eberhard
Institute of Pathology, Heidelberg, Germany.
Clin J Am Soc Nephrol. 2007 Jan;2(1):121-34. doi: 10.2215/CJN.01760506. Epub 2006 Dec 6.
Coronary calcification is a potent predictor of cardiac events. In patients with chronic renal disease, both prevalence and intensity of coronary calcification are increased. It has remained uncertain whether it is the intima of the coronaries or the media that is calcified and whether the morphologic details of calcified plaques differ between renal and nonrenal patients. Autopsy samples of coronaries were obtained from standard sites in 23 renal and 23 age- and gender-matched nonuremic patients. Specimens were examined using light and electron microscopy, immunohistochemistry, backscatter imaging, and x-ray analysis. In coronaries, calcified plaques occupied a similar proportion of the intima area in renal versus nonrenal patients (17.3 +/- 11.9 versus 18.1 +/- 11.9%) but occupied a significantly higher proportion of the media (16.6 +/- 10.6 versus 3.8 +/- 2.31%). Expression of the proteins osteocalcin, C-reactive protein, TGF-beta, and collagen IV was significantly more intensive around coronary plaques of renal compared with nonrenal patients. The non-plaque-bearing intima of renal patients showed minimal staining for fetuin, but fetuin staining was seen surrounding calcified plaques. In addition, more pronounced deposition of C5b-9 was found around coronary plaques of renal patients, and glycophorin deposition pointed to more past intraplaque hemorrhage in renal patients. Calcification by electron backscatter analysis is more intense in the coronary media, but not if the intima is more intense in renal compared with nonrenal patients. A more marked inflammatory response in renal patients is suggested by more frequent presence and greater intensity of markers of inflammation.
冠状动脉钙化是心脏事件的有力预测指标。在慢性肾病患者中,冠状动脉钙化的患病率和严重程度均有所增加。冠状动脉内膜还是中膜发生钙化,以及钙化斑块的形态学细节在肾病患者和非肾病患者之间是否存在差异,目前仍不明确。从23例肾病患者以及23例年龄和性别匹配的非尿毒症患者的标准部位获取冠状动脉尸检样本。使用光学显微镜、电子显微镜、免疫组织化学、背散射成像和X射线分析对样本进行检查。在冠状动脉中,钙化斑块在肾病患者和非肾病患者的内膜面积中所占比例相似(分别为17.3±11.9%和18.1±11.9%),但在中膜中所占比例显著更高(分别为16.6±10.6%和3.8±2.31%)。与非肾病患者相比,肾病患者冠状动脉斑块周围骨钙素、C反应蛋白、转化生长因子-β和IV型胶原的表达明显更强。肾病患者无斑块的内膜中胎球蛋白染色极少,但在钙化斑块周围可见胎球蛋白染色。此外,在肾病患者冠状动脉斑块周围发现C5b-9沉积更为明显,而血型糖蛋白沉积表明肾病患者斑块内出血更多。通过电子背散射分析,冠状动脉中膜的钙化更强烈,但在肾病患者中,若内膜钙化比非肾病患者更强烈则并非如此。炎症标志物更频繁出现且强度更大,提示肾病患者存在更明显的炎症反应。