Division of Experimental and Clinical Cardiology, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, Kemerovo 650002, Russia.
Int J Mol Sci. 2019 Nov 15;20(22):5728. doi: 10.3390/ijms20225728.
Calcium phosphate bions (CPBs) are formed under blood supersaturation with calcium and phosphate owing to the mineral chaperone fetuin-A and representing mineralo-organic particles consisting of bioapatite and multiple serum proteins. While protecting the arteries from a rapid medial calcification, CPBs cause endothelial injury and aggravate intimal hyperplasia in balloon-injured rat aortas. Here, we asked whether CPBs induce intimal hyperplasia in intact rat arteries in the absence of cardiovascular risk factors. Normolipidemic Wistar rats were subjected to regular (once/thrice per week over 5 weeks) tail vein injections of either spherical (CPB-S) or needle-shaped CPBs (CPB-N), magnesium phosphate bions (MPBs), or physiological saline ( = 5 per group). Neointima was revealed in 3/10 and 4/10 rats which received CPB-S or CPB-N, respectively, regardless of the injection regimen or blood flow pattern in the aortic segments. In contrast, none of the rats treated with MPBs or physiological saline had intimal hyperplasia. The animals also did not display signs of liver or spleen injury as well as extraskeletal calcium deposits. Serum alanine/aspartate transaminases, interleukin-1β, MCP-1/CCL2, C-reactive protein, and ceruloplasmin levels did not differ among the groups. Hence, CPBs may provoke intimal hyperplasia via direct endothelial injury regardless of their shape or type of blood flow.
钙磷生物矿化（CPB）是由于矿物伴侣蛋白胎球蛋白-A 的存在，在血液中钙和磷过饱和的情况下形成的，代表由生物磷灰石和多种血清蛋白组成的矿化有机颗粒。虽然 CPB 可以保护动脉免受快速中层钙化，但会导致内皮损伤，并加重球囊损伤大鼠的内膜增生。在这里，我们想知道在没有心血管危险因素的情况下，CPB 是否会在完整的大鼠动脉中引起内膜增生。将正常血脂的 Wistar 大鼠进行常规（每周一次/三次，共 5 周）尾静脉注射，分别给予球形（CPB-S）或针状 CPB（CPB-N）、磷酸镁生物矿化（MPB）或生理盐水（每组 5 只）。结果显示，无论注射方案或主动脉段的血流模式如何，分别接受 CPB-S 或 CPB-N 注射的大鼠中有 3/10 和 4/10 出现了新生内膜增生。相比之下，接受 MPB 或生理盐水治疗的大鼠均未出现内膜增生。这些动物也没有出现肝或脾损伤以及骨骼外钙沉积的迹象。各组间血清丙氨酸/天冬氨酸转氨酶、白细胞介素-1β、MCP-1/CCL2、C 反应蛋白和铜蓝蛋白水平无差异。因此，CPB 可能通过直接内皮损伤引起内膜增生，而与它们的形状或血流类型无关。
