Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York
Department of Diagnostic Radiology, Keio University School of Medicine, Tokyo, Japan.
J Nucl Med. 2019 Sep;60(9):1207-1212. doi: 10.2967/jnumed.119.230276. Epub 2019 Jul 26.
Calcification in a coronary artery is accepted as definite evidence of coronary atherosclerosis. The extent and density of calcification, as combined in the Agatston score, is associated with the risk of a patient experiencing a major acute coronary event. Atherosclerosis occurs because damaged endothelial cells allow low-density lipoprotein cholesterol (LDLc) to leak into subintimal tissue. Proteoglycans in subendothelial collagen have a high affinity for LDLc, retaining the lipoprotein cholesterol complex. As the endothelial damage is repaired, the subintimal LDLc is trapped. Retained LDLc induces an inflammatory response in the overlying endothelium, causing the endothelium to express chemotactic peptides. Chemotactic peptides attract circulating monocytes, which follow the concentration gradient, enter the tissue, and become tissue macrophages to phagocytize and digest the irritating LDLc in the atheroma. In the process of digesting LDLc, enzymes in the macrophages oxidize the LDLc complex. Oxidized LDL is toxic to macrophages; when present in sufficient quantity, it may cause death of macrophages, contributing to inflammation in the atheroma. In a necrotic inflammatory lesion, the regulatory mechanisms that control tissue concentrations of calcium and phosphorus are lost, allowing the solubility product of calcium phosphate to be exceeded, resulting in the formation of microscopic calcium-phosphate crystals. With ongoing inflammation, additional calcium-phosphate crystals are formed, which may aggregate. When these aggregated calcium phosphate crystals exceed 1 mm, the lesions become visible on clinical CT as coronary calcifications. Serial gated CT scans of the heart have demonstrated that once formed, CT-visible calcifications do not decrease significantly in size but may increase.
冠状动脉钙化被认为是冠状动脉粥样硬化的确切证据。钙化的程度和密度，如在 Agatston 评分中结合在一起，与患者发生重大急性冠状动脉事件的风险相关。动脉粥样硬化的发生是因为受损的内皮细胞允许低密度脂蛋白胆固醇（LDLc）渗漏到内膜下组织。 内膜下的胶原中的蛋白聚糖对 LDLc 具有高亲和力，保留脂蛋白胆固醇复合物。随着内皮损伤的修复，内膜下的 LDLc 被捕获。保留的 LDLc 在覆盖的内皮中诱导炎症反应，导致内皮表达趋化肽。趋化肽吸引循环中的单核细胞，单核细胞沿着浓度梯度进入组织，并成为组织巨噬细胞吞噬和消化动脉粥样硬化中的刺激性 LDLc。在消化 LDLc 的过程中，巨噬细胞中的酶氧化 LDLc 复合物。氧化的 LDLc 对巨噬细胞有毒；当存在足够量时，它可能导致巨噬细胞死亡，导致动脉粥样硬化中的炎症。在坏死性炎症病变中，控制组织中钙和磷浓度的调节机制丧失，允许磷酸钙的溶解度积超过，导致形成微小的磷酸钙晶体。随着炎症的持续，形成更多的磷酸钙晶体，这些晶体可能会聚集。当这些聚集的磷酸钙晶体超过 1 毫米时，病变在临床 CT 上可作为冠状动脉钙化而变得可见。心脏的连续门控 CT 扫描表明，一旦形成，CT 可见的钙化在大小上不会显著减少，但可能会增加。
