Division of Cardiology and McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, 27599-7075, USA.
Sci Rep. 2024 Jul 9;14(1):15847. doi: 10.1038/s41598-024-66860-x.
Atherosclerosis is rare in internal thoracic arteries (ITA) even in patients with severe atherosclerotic coronary artery (ACA) disease. To explore cellular differences, ITA SMC from 3 distinct donors and ACA SMC from 3 distinct donors were grown to sub-confluence and growth arrested for 48 h. Proliferation and thrombospondin-1 (TSP1) production were determined using standard techniques. ITA SMC were larger, grew more slowly and survived more passages than ACA SMC. ACA SMC had a more pronounced proliferative response to 10% serum than ITA SMC. Both ACA SMC and ITA SMC proliferated in response to exogenous TSP1 (12.5 µg/ml and 25 µg/ml) and platelet derived growth factor-BB (PDGF-BB; 20 ng/ml) but TSP1- and PDGF-BB-induced proliferation were partially inhibited by anti-TSP1 antibody A4.1, microRNA-21(miR-21)-3p inhibitors and miR-21-5p inhibitors in each of the 3 ACA SMC lines, but not in any of the ITA SMC lines. PDGF-BB stimulated TSP1 production in ACA SMC but not in ITA SMC but there was no increase in TSP1 levels in conditioned media in either SMC type. In summary, there are significant differences in morphology, proliferative capacity and in responses to TSP1 and PDGF-BB in SMC derived from ITA compared to SMC derived from ACA.
动脉粥样硬化在内乳动脉（ITA）中很少见，即使在严重动脉粥样硬化性冠状动脉（ACA）疾病的患者中也是如此。为了探讨细胞差异，我们将来自 3 位不同供体的 ITA 平滑肌细胞（SMC）和来自 3 位不同供体的 ACA SMC 培养至亚汇合状态，并将其生长抑制 48 小时。使用标准技术确定增殖和血小板反应蛋白-1（TSP1）的产生。ITA SMC 比 ACA SMC 更大，生长更慢，传代更多。ACA SMC 对 10%血清的增殖反应比 ITA SMC 更为明显。ACA SMC 和 ITA SMC 都能对外源性 TSP1（12.5μg/ml 和 25μg/ml）和血小板衍生生长因子-BB（PDGF-BB；20ng/ml）产生增殖反应，但 TSP1 和 PDGF-BB 诱导的增殖在 3 条 ACA SMC 系中，每种系都被抗 TSP1 抗体 A4.1、miR-21(miR-21)-3p 抑制剂和 miR-21-5p 抑制剂部分抑制，但在任何 ITA SMC 系中都没有抑制。PDGF-BB 刺激 ACA SMC 中 TSP1 的产生，但不刺激 ITA SMC 中 TSP1 的产生，但在两种 SMC 类型的条件培养基中 TSP1 水平均没有增加。总之，ITA 来源的 SMC 与 ACA 来源的 SMC 相比，在形态、增殖能力以及对 TSP1 和 PDGF-BB 的反应方面存在显著差异。
