Department of Cardiology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Department of Cardiology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Can J Cardiol. 2016 Dec;32(12):1454-1461. doi: 10.1016/j.cjca.2016.05.020. Epub 2016 Jun 25.
Transcatheter aortic valve replacement (TAVR) exposes the systemic vasculature to increased mechanical forces. Endothelial adaptation to mechanical stimuli is associated with angiogenic activation through various growth factors. We studied the potential angiogenic shift evoked by TAVR.
From a cohort of 69 consecutive patients undergoing TAVR, we excluded patients with conditions known to affect angiogenic factors, and serum vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 were assessed by ELISA. We assessed in vitro the properties of endothelial cells after exposure to serum collected from patients undergoing TAVR using adhesion, migration, and Matrigel angiogenesis assays. The correlation between changes in angiogenic factors and cardiac functions was evaluated on 30- day echocardiograms.
The study population consisted of 46 patients (82 ± 5 years). Two days after TAVR the post/pre TAVR ratio of VEGF, Ang-1, and Ang-2 was 5.38 ± 4 (P < 0.001), 1.05 ± 0.49 (P = 0.27), and 4.65 ± 2.01 (P < 0.001), respectively. The increase in VEGF and Ang-2 showed a significant correlation (r = 0.609; P < 0.001), but no correlation was found with hemolysis or tissue injury markers. Patients with relatively low levels of VEGF or an Ang-2 rise had more severe aortic stenosis and coronary disease at baseline. Exposure of endothelial cells to post-TAVR serum induced adhesion, migration, and tube formation compared with pre-TAVR serum. An increase in VEGF levels correlated with improvement in pulmonary systolic pressure and a right ventricular fractional area change at 30 days, (r = 0.54 and r = 0.48, respectively; P < 0.01).
Sustained elevation of VEGF and Ang-2 levels occur after TAVR, reflecting a systemic angiogenic shift. A rise in VEGF levels is associated with a decrease in pulmonary blood pressure in patients undergoing TAVR.
经导管主动脉瓣置换术(TAVR)使全身血管系统承受更高的机械力。内皮细胞对机械刺激的适应与各种生长因子相关的血管生成激活有关。我们研究了 TAVR 引起的潜在血管生成变化。
我们从 69 例连续接受 TAVR 的患者中排除了已知会影响血管生成因子的患者,并通过 ELISA 评估血清血管内皮生长因子(VEGF)、血管生成素(Ang)-1 和 Ang-2。我们使用粘附、迁移和 Matrigel 血管生成测定法,评估了暴露于接受 TAVR 患者的血清后内皮细胞的特性。在 30 天的超声心动图上评估了血管生成因子变化与心脏功能之间的相关性。
研究人群包括 46 名患者(82 ± 5 岁)。TAVR 后 2 天,VEGF、Ang-1 和 Ang-2 的 TAVR 前后比值分别为 5.38 ± 4(P < 0.001)、1.05 ± 0.49(P = 0.27)和 4.65 ± 2.01(P < 0.001)。VEGF 和 Ang-2 的增加呈显著相关性(r = 0.609;P < 0.001),但与溶血或组织损伤标志物无相关性。VEGF 水平较低或 Ang-2 升高的患者在基线时有更严重的主动脉瓣狭窄和冠状动脉疾病。与 TAVR 前血清相比,内皮细胞暴露于 TAVR 后血清后诱导粘附、迁移和管状形成。VEGF 水平的升高与 30 天时肺动脉收缩压和右心室分数面积变化的改善相关(r = 0.54 和 r = 0.48,分别;P < 0.01)。
TAVR 后 VEGF 和 Ang-2 水平持续升高,反映出全身血管生成转移。VEGF 水平升高与接受 TAVR 的患者肺动脉压降低相关。