Cardiovascular Institute, Tianjin Chest Hospital, Tianjin, 300222, China.
Department of Cardiology, Tianjin Chest Hospital, Tianjin, 300222, China.
Biometals. 2022 Dec;35(6):1325-1339. doi: 10.1007/s10534-022-00449-7. Epub 2022 Sep 30.
Vascular calcification (VC) has been associated with a risk of cardiovascular diseases. Iron may play a critical role in progressive VC. Therefore, we investigated the effects of iron overload on the aorta of rats. A rat model of iron overload was established by intraperitoneal injection of Iron-Dextran. The levels of iron, calcium, and ALP activity were detected. Von Kossa staining and Perl's staining were conducted. The expression of iron metabolism-related and calcification related factors were examined in the aortic tissue of rats. The results showed serum and aortic tissue iron were increased induced by iron overload and excessive iron induced hepatic and renal damage. In iron overload rats, the expression of divalent metal transporter 1 (DMT1) and hepcidin were higher, but ferroportin1 (FPN1) was lower. Von Kossa staining demonstrated calcium deposition in the aorta of iron overload rats. The calcium content and ALP activity in serum and aortic tissue were increased and iron level in aortic tissue highly correlated with calcium content and ALP activity. The expressions of the osteogenic markers were increased while a decrease of Alpha-smooth muscle actin (α-SMA) in the aortic tissue of iron overload rats. IL-24 was increased during the calcification process induced by iron. Overall, we demonstrated excessive iron accumulation in the aortic tissue and induced organs damage. The iron metabolism-related factors were significantly changed during iron overload. Moreover, we found that iron overload leads to calcium deposition in aorta, playing a key role in the pathological process of VC by mediating osteoblast differentiation factors.
血管钙化（VC）与心血管疾病的风险相关。铁可能在进行性 VC 中起关键作用。因此，我们研究了铁过载对大鼠主动脉的影响。通过腹腔注射铁葡聚糖建立大鼠铁过载模型。检测铁、钙和碱性磷酸酶（ALP）活性水平。进行Von Kossa 染色和 Perl 染色。检测大鼠主动脉中铁代谢相关和钙化相关因子的表达。结果表明，铁过载导致血清和主动脉组织铁含量增加，过量铁诱导肝和肾损伤。在铁过载大鼠中，二价金属转运蛋白 1（DMT1）和铁调素的表达升高，而亚铁转运蛋白 1（FPN1）的表达降低。Von Kossa 染色显示铁过载大鼠主动脉中有钙沉积。血清和主动脉组织中的钙含量和 ALP 活性增加，主动脉组织中的铁含量与钙含量和 ALP 活性高度相关。铁过载大鼠主动脉组织中成骨标志物的表达增加，而α-平滑肌肌动蛋白（α-SMA）减少。在铁诱导的钙化过程中，IL-24 增加。总之，我们证明了主动脉组织中铁的过度积累，并导致了器官损伤。铁过载时铁代谢相关因子发生显著变化。此外，我们发现铁过载导致主动脉钙沉积，通过调节成骨细胞分化因子在 VC 的病理过程中起关键作用。
