E. Meshalkin National Medical Research Center of the RF Ministry of Health, 15 Rechkunovskaya St., 630055 Novosibirsk, Russia.
N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 9 Lavrentiev Avenue, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2023 Apr 14;24(8):7274. doi: 10.3390/ijms24087274.
The causes of heart valve bioprosthetic calcification are still not clear. In this paper, we compared the calcification in the porcine aorta (Ao) and the bovine jugular vein (Ve) walls, as well as the bovine pericardium (Pe). Biomaterials were crosslinked with glutaraldehyde (GA) and diepoxide (DE), after which they were implanted subcutaneously in young rats for 10, 20, and 30 days. Collagen, elastin, and fibrillin were visualized in non-implanted samples. Atomic absorption spectroscopy, histological methods, scanning electron microscopy, and Fourier-transform infrared spectroscopy were used to study the dynamics of calcification. By the 30th day, calcium accumulated most intensively in the collagen fibers of the GA-Pe. In elastin-rich materials, calcium deposits were associated with elastin fibers and localized differences in the walls of Ao and Ve. The DE-Pe did not calcify at all for 30 days. Alkaline phosphatase does not affect calcification since it was not found in the implant tissue. Fibrillin surrounds elastin fibers in the Ao and Ve, but its involvement in calcification is questionable. In the subcutaneous space of young rats, which are used to model the implants' calcification, the content of phosphorus was five times higher than in aging animals. We hypothesize that the centers of calcium phosphate nucleation are the positively charged nitrogen of the pyridinium rings, which is the main one in fresh elastin and appears in collagen as a result of GA preservation. Nucleation can be significantly accelerated at high concentrations of phosphorus in biological fluids. The hypothesis needs further experimental confirmation.
心脏瓣膜生物假体钙化的原因尚不清楚。在本文中,我们比较了猪主动脉(Ao)和牛颈静脉(Ve)壁以及牛心包(Pe)的钙化情况。生物材料用戊二醛(GA)和二环氧(DE)交联,然后将其植入年轻大鼠皮下 10、20 和 30 天。在未植入的样本中观察到胶原蛋白、弹性蛋白和原纤维蛋白。原子吸收光谱、组织学方法、扫描电子显微镜和傅里叶变换红外光谱用于研究钙化动力学。到第 30 天,GA-Pe 中的胶原蛋白纤维中钙积累最强烈。在富含弹性蛋白的材料中,钙沉积物与弹性蛋白纤维有关,并与 Ao 和 Ve 壁的局部差异有关。DE-Pe 在 30 天内根本没有钙化。由于在植入组织中未发现碱性磷酸酶,因此它不会影响钙化。纤连蛋白环绕着 Ao 和 Ve 中的弹性蛋白纤维,但它是否参与钙化是值得怀疑的。在年轻大鼠的皮下空间中,用于模拟植入物钙化的模型,磷的含量是老年动物的五倍。我们假设磷酸钙成核的中心是吡啶环的带正电荷的氮,这是新鲜弹性蛋白的主要成分,并且由于 GA 保存而出现在胶原蛋白中。在生物流体中高浓度磷的情况下,可以显著加速成核。该假设需要进一步的实验验证。