Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins
Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins
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DOI：
10.1046/j.1523-1755.2002.00170.x
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发表时间：
2002-02-01
影响因子：
19.6
通讯作者：
Kopecky, K
中科院分区：
文献类型：
--
作者：
Moe, SM;O'Neill, KD;Kopecky, K
背景。在非esrd患者中，最近的研究表明血管钙化过程类似于发育性成骨。众所周知，ESRD患者有过度的血管钙化，但这以前被归因于非细胞介导的转移性钙化过程。为了确定在ESRD患者中观察到的钙化是否与细胞介导的过程有关，我们在肾移植时切除了一段腹壁下动脉。采用螺旋计算机断层扫描（CT）定量测定全血管钙含量。然后通过免疫组织化学检查血管的钙化和骨基质蛋白的存在，并通过组织形态计量法定量血管的内侧和内膜厚度。这些发现与人口学、临床和实验室值相关。41例肾移植患者的腹壁近端下动脉，2例病理检查不充分。其余27条血管经Mac-Neal’s或Alizarin red pH 4.2染色未见钙化，5条血管轻度/中度钙化，7条血管重度钙化，均位于内侧层。组织学评估的钙化与螺旋CT评估的钙化评分密切相关，按血管重量归一化（P = 0.027）。骨基质蛋白骨桥蛋白、I型胶原蛋白、骨唾液蛋白和碱性磷酸酶免疫染色阳性与钙化密切相关（P均小于或等于0.001），冠心病史（P < 0.001）和糖尿病史（P = 0.034）也是如此。螺旋CT钙化评分与上述因素及血清磷、钙x磷积相关（P = 0.032、0.037）。骨蛋白免疫染色的位置与钙化的存在密切相关。然而，在明显钙化之前，免疫染色阳性也观察到血管平滑肌细胞内侧层由于基质样物质的沉积而组织紊乱。接受肾移植的ESRD患者，腹壁下动脉内层血管钙化很常见（44%），可通过螺旋CT检测到，并与骨基质蛋白沉积有关。这意味着一个活跃的细胞介导的过程，增加了定向干预可以阻止这一过程的希望。
Background. In non-ESRD patients, recent studies have demonstrated that the process of vascular calcification resembles developmental osteogenesis. Patients with ESRD are known to have excessive vascular calcification, but this has previously been attributed to the non-cell-mediated process of metastatic calcification.Methods. To determine if the calcification observed in patients with ESRD is related to a cell-mediated process, we removed a piece of inferior epigastric artery at the time of renal transplant. Calcium content of the entire vessel was quantified with spiral computed tomography (CT). The vessel was then examined histologically for calcification and the presence of bone matrix proteins by immunohistochemistry, and medial and intimal thickness quantified by histomorphometry. These findings were correlated with demographic, clinical and laboratory values.Results. The proximal inferior epigastric artery was obtained from 41 patients undergoing renal transplantation, but two were inadequate for histologic examination. Twenty-seven of the remaining vessels had no evidence of calcification by Mac-Neal's or Alizarin red pH 4.2 staining, five vessels had mild/moderate calcification, and seven had severe calcification, all in the medial layer. Calcification assessed histologically was closely correlated with calcification score as assessed by spiral CT, normalized for vessel weight (P = 0.027). Positive immunostaining for the bone matrix proteins osteopontin, type I collagen, bone sialoprotein, and alkaline phosphatase was strongly correlated with calcification (all P less than or equal to 0.001), as was a history of coronary artery disease (P < 0.001), and diabetes (P = 0.034). The calcification score by spiral CT correlated with these same factors and the serum phosphorus and calcium x phosphorus product (P = 0.032 and 0.037). The location of immunostaining for the bone proteins was strongly associated with the presence of calcification. However, positive immunostaining also was observed in association with disorganization of the vascular smooth muscle cells in the medial layer due to deposition of a matrix-like substance, prior to overt calcification.Conclusions. Inpatients with ESRD undergoing renal transplantation, vascular calcification of the medial layer of the inferior epigastric artery is common (44%), can be detected by spiral CT, and is associated with deposition of bone matrix proteins. This implies an active cell-mediated process, raising hope that directed intervention can arrest this process.