Inhibition of advanced glycation end product formation and serum protein infiltration in bioprosthetic heart valve leaflets: Investigations of anti-glycation agents and anticalcification interactions with ethanol pretreatment.
Inhibition of advanced glycation end product formation and serum protein infiltration in bioprosthetic heart valve leaflets: Investigations of anti-glycation agents and anticalcification interactions with ethanol pretreatment.
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DOI：
10.1016/j.biomaterials.2022.121782
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发表时间：
2022-10
期刊：
影响因子：
14
通讯作者：
中科院分区：
文献类型：
--
作者：
生物人工心脏瓣膜（BHV）由异种移植组织制成，如戊二醛预处理牛心包（BP），是最常用的心脏瓣膜替代物。BHV的耐久性受到结构性瓣膜变性（SVD）的限制，SVD与钙化、晚期糖基化终产物（AGE）和血清蛋白浸润有关。我们研究了抗age药物、氨基胍、吡哆胺[Pyridoxamine [PYR]和n -乙酰半胱氨酸可以减轻age血清蛋白SVD机制的假设，这些药物可以减轻钙化或与乙醇预处理的BP相互作用。在体外，这些药物均能显著抑制age -血清蛋白在BP中的浸润。然而，在28天的大鼠皮下BP植入中，仅口服PYR可显著抑制AGE和血清蛋白摄取。此外，BP PYR预培养减轻了age -血清蛋白SVD机制，并在28天的大鼠皮下BP外植体中证明了age -血清蛋白摄取的减轻和体内钙化的减少。用乙醇预处理28天大鼠皮下BP外植体，再用PYR预孵育，观察其对BP钙化和age血清蛋白浸润的抑制作用。综上所述，PYR口服治疗和PYR与乙醇预处理BP均可显著减轻age -血清蛋白和钙化SVD病理生理。
Bioprosthetic heart valves (BHV) fabricated from heterograft tissue, such as glutaraldehyde pretreated bovine pericardium (BP), are the most frequently used heart valve replacements. BHV durability is limited by structural valve degeneration (SVD), mechanistically associated with calcification, advanced glycation end products (AGE), and serum protein infiltration. We investigated the hypothesis that anti-AGE agents, Aminoguanidine, Pyridoxamine [PYR], and N-Acetylcysteine could mitigate AGE-serum protein SVD mechanisms in vitro and in vivo, and that these agents could mitigate calcification or demonstrate anti-calcification interactions with BP pretreatment with ethanol. In vitro, each of these agents significantly inhibited AGE-serum protein infiltration in BP. However, in 28-day rat subdermal BP implants only orally administered PYR demonstrated significant inhibition of AGE and serum protein uptake. Furthermore, BP PYR preincubation of BP mitigated AGE-serum protein SVD mechanisms in vitro, and demonstrated mitigation of both AGE-serum protein uptake and reduced calcification in vivo in 28-day rat subdermal BP explants. Inhibition of BP calcification as well as inhibition of AGE-serum protein infiltration was observed in 28-day rat subdermal BP explants pretreated with ethanol followed by PYR preincubation. In conclusion, AGE-serum protein and calcification SVD pathophysiology are significantly mitigated by both PYR oral therapy and PYR and ethanol pretreatment of BP.
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影响因子：
4.6
作者：
Joyce, Erinn M.;Liao, Jun;Schoen, Frederick J.;Mayer, John E., Jr.;Sacks, Michael S.
通讯作者：
Sacks, Michael S.
影响因子：
13.6
作者：
Lewis, Edmund J.;Greene, Tom;Lewis, Julia B.
通讯作者：
Lewis, Julia B.
DOI：
10.1002/jbm.a.37280
发表时间：
2022-03
期刊：
Journal of biomedical materials research. Part A
影响因子：
--
作者：
Cramer M;Chang J;Li H;Serrero A;El-Kurdi M;Cox M;Schoen FJ;Badylak SF
通讯作者：
Badylak SF
影响因子：
4.6
作者：
Abar O;Dharmar S;Tang SY
通讯作者：
Tang SY
影响因子：
2.9
作者：
Adrover, M;Vilanova, B;Donoso, J
通讯作者：
Donoso, J