Poitier Bastien, Rancic Jeanne, Richez Ulysse, Piquet Julie, El Batti Salma, Smadja David M
Université de Paris Cité, Innovative Therapies in Haemostasis, INSERM UMR-S1140, Paris, France.
Cardiovascular Surgery Department, AP-HP, Georges Pompidou European Hospital, Paris, France.
Front Cardiovasc Med. 2023 Jul 31;10:1198020. doi: 10.3389/fcvm.2023.1198020. eCollection 2023.
Bioprosthetic heart valves (BHVs) are less thrombogenic than mechanical prostheses; however, BHV thrombosis has been proposed as a risk factor for premature BHV degeneration.
We aimed to explore whether fibrin deposition on bovine pericardium tissue could lead to calcification.
Fibrin clot was obtained by blending three reagents, namely, CRYOcheck™ Pooled Normal Plasma (4/6), tissue factor + phospholipids (Thrombinoscope BV), and 100 mM calcium (1/6), and deposited on pericardium discs. Non-treated and fibrin-treated bovine pericardium discs were inserted into the subcutaneous tissue of 12-day-old Wistar rats and sequentially explanted on days 5, 10, and 15. Calcium content was measured with acetylene flame atomic absorption spectrophotometry. Histological analysis was performed using hematoxylin-eosin staining, Von Kossa staining, and immunohistochemistry.
Calcification levels were significantly higher in fibrin-treated bovine pericardium discs compared to those in non-treated bovine pericardium discs (27.45 ± 23.05 µg/mg vs. 6.34 ± 6.03 µg/mg on day 5, 64.34 ± 27.12 µg/mg vs. 34.21 ± 19.11 µg/mg on day 10, and 64.34 ± 27.12 µg/mg vs. 35.65 ± 17.84 µg/mg on day 15; < 0.001). Von Kossa staining confirmed this finding. In hematoxylin-eosin staining, the bovine pericardium discs were more extensively and deeply colonized by inflammatory-like cells, particularly T lymphocytes (CD3 cells), when pretreated with fibrin.
Fibrin deposition on bovine pericardium tissue treated with glutaraldehyde, used for BHV, led to increased calcification in a rat model. BHV thrombosis could be one of the triggers for calcification and BHV deterioration.
生物人工心脏瓣膜（BHVs）的血栓形成性低于机械瓣膜；然而，BHV血栓形成已被认为是BHV过早退变的一个危险因素。
我们旨在探讨纤维蛋白沉积于牛心包组织是否会导致钙化。
通过混合三种试剂获得纤维蛋白凝块，即CRYOcheck™混合正常人血浆（4/6）、组织因子+磷脂（Thrombinoscope BV）和100 mM钙（1/6），并将其沉积于心包盘上。将未处理和经纤维蛋白处理的牛心包盘植入12日龄Wistar大鼠的皮下组织，并在第5、10和15天依次取出。用乙炔火焰原子吸收分光光度法测量钙含量。使用苏木精-伊红染色、冯·科萨染色和免疫组织化学进行组织学分析。
与未处理的牛心包盘相比，经纤维蛋白处理的牛心包盘的钙化水平显著更高（第5天为27.45±23.05μg/mg对6.34±6.03μg/mg，第10天为64.34±27.12μg/mg对34.21±19.11μg/mg，第15天为64.34±27.12μg/mg对35.65±17.84μg/mg；P<0.001）。冯·科萨染色证实了这一发现。在苏木精-伊红染色中，当用纤维蛋白预处理时，牛心包盘被炎症样细胞，特别是T淋巴细胞（CD3细胞）更广泛、更深地定植。
在用于BHV的经戊二醛处理的牛心包组织上的纤维蛋白沉积导致大鼠模型中的钙化增加。BHV血栓形成可能是钙化和BHV退变的触发因素之一。
