Johnson Rebecca C, Leopold Jane A, Loscalzo Joseph
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Circ Res. 2006 Nov 10;99(10):1044-59. doi: 10.1161/01.RES.0000249379.55535.21.
Once thought to result from passive precipitation of calcium and phosphate, it now appears that vascular calcification is a consequence of tightly regulated processes that culminate in organized extracellular matrix deposition by osteoblast-like cells. These cells may be derived from stem cells (circulating or within the vessel wall) or differentiation of existing cells, such as smooth muscle cells (SMCs) or pericytes. Several factors induce this transition, including bone morphogenetic proteins, oxidant stress, high phosphate levels, parathyroid hormone fragments, and vitamin D. Once the osteogenic phenotype is induced, cells gain a distinctive molecular fingerprint, marked by the transcription factor core binding factor alpha1. Alternatively, loss of inhibitors of mineralization, such as matrix gamma-carboxyglutamic acid Gla protein, fetuin, and osteopontin, also contribute to vascular calcification. The normal balance between promotion and inhibition of calcification becomes dysregulated in chronic kidney disease, diabetes mellitus, atherosclerosis, and as a consequence of aging. Once the physiological determinants of calcification are perturbed, calcification may occur at several sites in the cardiovascular system, including the intima and media of vessels and cardiac valves. Here, calcification may occur through overlapping yet distinct molecular mechanisms, each with different clinical ramifications. A variety of imaging techniques are available to visualize vascular calcification, including fluoroscopy, echocardiography, intravascular ultrasound, and electron beam computed tomography. These imaging modalities vary in sensitivity and specificity, as well as clinical application. Through greater understanding of both the mechanism and clinical consequences of vascular calcification, future therapeutic strategies may be more effectively designed and applied.
血管钙化曾被认为是钙和磷酸盐被动沉淀的结果，现在看来，它是由严格调控的过程所导致的，这些过程最终导致成骨样细胞有序地沉积细胞外基质。这些细胞可能来源于干细胞（循环干细胞或血管壁内的干细胞），或者是现有细胞（如平滑肌细胞或周细胞）的分化。有几种因素可诱导这种转变，包括骨形态发生蛋白、氧化应激、高磷水平、甲状旁腺激素片段和维生素D。一旦诱导出成骨表型，细胞就会获得一种独特的分子特征，其标志是转录因子核心结合因子α1。另外，矿化抑制剂（如基质γ-羧基谷氨酸Gla蛋白、胎球蛋白和骨桥蛋白）的缺失也会导致血管钙化。在慢性肾病、糖尿病、动脉粥样硬化以及衰老过程中，钙化促进与抑制之间的正常平衡会失调。一旦钙化的生理决定因素受到干扰，钙化可能会发生在心血管系统的多个部位，包括血管内膜、中膜和心脏瓣膜。在这里，钙化可能通过重叠但不同的分子机制发生，每种机制都有不同的临床后果。有多种成像技术可用于观察血管钙化，包括荧光透视、超声心动图、血管内超声和电子束计算机断层扫描。这些成像方式在敏感性、特异性以及临床应用方面各不相同。通过更深入地了解血管钙化的机制和临床后果，未来的治疗策略可能会得到更有效的设计和应用。
