Li Bowen, Liu Qingbo, Chen Xihui, Chen Tangdong, Dang Wenhui, Zhao Jing, Cui Guangbin, Chen Kun, Wu Yuanming
Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an, China.
Shaanxi Junda Forensic Medicine Expertise Station, Air Force Medical University, Xi'an, China.
Front Cardiovasc Med. 2022 Mar 21;9:788958. doi: 10.3389/fcvm.2022.788958. eCollection 2022.
Cardiac calcification is a type of ectopic pathologic calcification of unknown etiology and mechanisms. Once diagnosed, the location, extent and morphology of the calcified lesions, as well as their functional significance in the heart, are usually the focus of case reports. Calcification is mostly distributed in myocardium, but rarely reported in atrium. In addition, because of limited sampling and complex pathological mechanisms, the etiology underlying the formation of these calcified lesions also remains unclear.
Two cardiac calcifications were found in a patient, died of trauma-induced subarachnoid hemorrhage after slightly drinking, during a standard autopsy. The location and morphological characteristics of the calcified lesions were determined by computed tomography (CT) and CT-based 3D reconstruction. The specific histopathological characteristics of the lesions were determined by multi-staining. The concentration of free calcium and inorganic pyrophosphate (PPi) in plasma reflected the change of calcium metabolism. The expression and membranal localization of the ATP Binding Cassette Subfamily C Member 6 (ABCC6) in hepatocytes were detected by immunofluorescence. The variants of the ABCC6 were detected by Sanger sequencing and potential pathogenic variants were further identified by analysis.
The present study describes a patient with idiopathic calcification with two pear-shaped and irregularly hollow lesions symmetrically distributed in the patient's atrium. Massive accumulation of calcium salts was identified by multi-staining. For this patient, the plasma concentration of free calcium was higher than the control, indicating that calcium metabolism was disturbed. Furthermore, the plasma PPi of the patient was lower than the normal. By using immunofluorescence, the expression and membranal localization of ABCC6 was decreased and impaired in hepatocytes, respectively. Combined with Sanger sequencing and analysis, 7 variants were identified.
This study described a novel patient with symmetrically distributed idiopathic atrial calcifications. Furthermore, all the results indicated that these pathologic calcifications may be secondary to reduced plasma PPi content due to ABCC6 dysfunction in hepatocytes. Moreover, these findings provided novel clues to the pathogenesis, clinical diagnosis and treatment of idiopathic atrial calcification in future.
心脏钙化是一种病因和机制不明的异位病理性钙化。一旦确诊，钙化病变的位置、范围和形态及其在心脏中的功能意义通常是病例报告的重点。钙化大多分布于心肌，但在心房中很少有报道。此外，由于取样有限和病理机制复杂，这些钙化病变形成的病因仍不清楚。
在一名因少量饮酒后创伤性蛛网膜下腔出血死亡的患者进行标准尸检时发现了两处心脏钙化。通过计算机断层扫描（CT）和基于CT的三维重建确定钙化病变的位置和形态特征。通过多重染色确定病变的具体组织病理学特征。血浆中游离钙和无机焦磷酸（PPi）的浓度反映钙代谢的变化。通过免疫荧光检测肝细胞中ATP结合盒转运体C家族成员6（ABCC6）的表达和膜定位。通过桑格测序检测ABCC6的变异，并通过分析进一步鉴定潜在的致病变异。
本研究描述了一名患有特发性钙化的患者，其心房中有两个梨形且不规则中空的病变对称分布。通过多重染色鉴定出大量钙盐沉积。对于该患者，血浆游离钙浓度高于对照组，表明钙代谢受到干扰。此外，患者的血浆PPi低于正常水平。通过免疫荧光检测，肝细胞中ABCC6的表达和膜定位分别降低和受损。结合桑格测序和分析，鉴定出7种变异。
本研究描述了一名患有对称分布的特发性心房钙化的新患者。此外，所有结果表明，这些病理性钙化可能继发于肝细胞中ABCC6功能障碍导致的血浆PPi含量降低。此外，这些发现为未来特发性心房钙化的发病机制、临床诊断和治疗提供了新线索。
