Department of Cardiac Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Department of Cardiac Surgery, University Hospital Halle (Saale), 06120 Halle, Germany.
Cells. 2021 May 17;10(5):1231. doi: 10.3390/cells10051231.
In patients undergoing coronary artery bypass grafting (CABG), ischemia/reperfusion injury (IRI) is the main contributor to organ dysfunction. Aging-induced vascular damage may be further aggravated during CABG. Favorable effects of conditioned medium (CM) from mesenchymal stem cells (MSCs) have been suggested against IRI. We hypothesized that adding CM to saline protects vascular grafts from IRI in rats. We found that CM contains 28 factors involved in apoptosis, inflammation, and oxidative stress. Thoracic aortic rings from 15-month-old rats were explanted and immediately mounted in organ bath chambers (aged group) or underwent 24 h of cold ischemic preservation in saline-supplemented either with vehicle (aged-IR group) or CM (aged-IR+CM group), prior to mounting. Three-month-old rats were used as referent young animals. Aging was associated with an increase in intima-to-media thickness, an increase in collagen content, higher caspase-12 mRNA levels, and immunoreactivity compared to young rats. Impaired endothelium-dependent vasorelaxation to acetylcholine in the aged-IR group compared to the aged-aorta was improved by CM (aged 61 ± 2% vs. aged-IR 38 ± 2% vs. aged-IR+CM 50 ± 3%, < 0.05). In the aged-IR group, the already high mRNA levels of caspase-12 were decreased by CM. CM alleviates endothelial dysfunction following IRI in 15-month-old rats. The protective effect may be related to the inhibition of caspase-12 expression.
在接受冠状动脉旁路移植术（CABG）的患者中，缺血/再灌注损伤（IRI）是导致器官功能障碍的主要原因。CABG 期间，衰老引起的血管损伤可能进一步加重。间充质干细胞（MSCs）条件培养基（CM）对 IRI 具有有利影响。我们假设在大鼠中向生理盐水添加 CM 可以保护血管移植物免受 IRI。我们发现 CM 中含有 28 种与细胞凋亡、炎症和氧化应激有关的因子。从 15 个月大的大鼠中取出胸主动脉环，并立即将其安装在器官浴槽中（老龄组）或在添加有载体（老龄-IR 组）或 CM（老龄-IR+CM 组）的盐水中进行 24 小时冷缺血保存，然后再安装。3 个月大的大鼠被用作年轻动物的参考。与年轻大鼠相比，衰老与内膜-中膜厚度增加、胶原含量增加、caspase-12 mRNA 水平升高和免疫反应性增加有关。与老龄主动脉相比，老龄-IR 组对乙酰胆碱的内皮依赖性血管舒张作用受损，而 CM 可改善这种作用（老龄组 61±2% vs. 老龄-IR 组 38±2% vs. 老龄-IR+CM 组 50±3%， <0.05）。在老龄-IR 组中，CM 降低了 caspase-12 的高 mRNA 水平。CM 可减轻 15 月龄大鼠 IRI 后的内皮功能障碍。这种保护作用可能与抑制 caspase-12 表达有关。
