这项研究调查了蛇蛇蛇物种和亚种(总共11个毒液)对血浆凝血时间的毒液作用的种内和种间变异性,纤维蛋白原水平,和纤维蛋白凝块强度。A.conanti的血浆凝血时间显着延迟,A.contortrixmokasen,A.扭曲phaeogaster,A.Howardgloydi,A.灰霉病,和A.piscivoruspiscivorus。值得注意的是,系统发育分离谱系A.conanti,A.contortrixmokasen,和A.howardgloydi表现出最有效的抗凝血作用,表明基础性状的独立扩增。用活化凝血酶因子XIa的抑制测定,IXa,Xa,和IIa(凝血酶)揭示了FXa抑制是该属内多次独立扩增的另一个基础性状,但对于A.Howardgloydi,尤其比其他所有人更有效。磷脂降解和酶原破坏被确定为实验和先前临床报告中观察到的毒液效应变异性的潜在机制。血栓弹力图显示,毒液不会直接凝固纤维蛋白原,但会通过破坏纤维蛋白原影响纤维蛋白凝块强度,并且凝血酶随后只能裂解成微弱的,不稳定的凝块。激活蛋白C的能力,内源性抗凝血酶,因物种而异,一些毒液超过了A.contortrix的毒液,以前生产的蛋白质诊断剂Protac®。系统发育分析表明,纤维蛋白原降解和蛋白C活化均在属内多次扩增,尽管这两种作用方式之间存在负相关。这项研究强调了进化,临床,和毒液变异的生物发现意义,强调了它们的动态演变,强调需要量身定制的临床方法,并强调了受蛇毒独特特性启发的新型诊断和治疗发展的潜力。
This study investigated the intraspecific and interspecific variability in the
venom effects of Agkistrodon viperid snake species and subspecies (eleven venoms total) on plasma clotting times, fibrinogen levels, and fibrin clot strength. Significant delays in plasma clotting time were observed for A. conanti, A. contortrix mokasen, A. contortrix phaeogaster, A. howardgloydi, A. piscivorus leucostoma, and A. piscivorus piscivorus. Notably, the phylogenetically disjunct lineages A. conanti, A. contortrix mokasen, and A. howardgloydi exhibited the most potent anticoagulant effects, indicating the independent amplification of a basal trait. Inhibition assays with the activated clotting enzymes Factors XIa, IXa, Xa, and IIa (thrombin) revealed that FXa inhibition is another basal trait amplified independently on multiple occasions within the genus, but with A. howardgloydi, notably more potent than all others. Phospholipid degradation and zymogen destruction were identified as mechanisms underlying the variability in
venom effects observed experimentally and in previous clinical reports. Thromboelastography demonstrated that the venoms did not clot fibrinogen directly but affected fibrin clot strength by damaging fibrinogen and that thrombin was subsequently only able to cleave into weak, unstable clots. The ability to activate Protein C, an endogenous anticoagulant enzyme, varied across species, with some venoms exceeding that of A. contortrix contortrix, which previously yielded the protein diagnostic agent Protac®. Phylogenetic analysis suggested that both fibrinogen degradation and Protein C activation were each amplified multiple times within the genus, albeit with negative correlation between these two modes of action. This study highlights the evolutionary, clinical, and biodiscovery implications of
venom variability in the Agkistrodon species, underscoring their dynamic evolution, emphasising the need for tailored clinical approaches, and highlighting the potential for novel diagnostic and therapeutic developments inspired by the unique properties of snake venoms.