Biomedical Research Institute (BIOMED), Hasselt University, Martelarenlaan 42, 3500, Hasselt, Belgium.
Sci Rep. 2017 Nov 22;7(1):16010. doi: 10.1038/s41598-017-16255-y.
Advanced glycation end products (AGEs) play a key role in the progression of heart failure. Whether treatments limiting AGEs formation would prevent adverse left ventricular remodeling after myocardial infarction (MI) remain unknown. We investigated whether pyridoxamine (PM) could limit adverse cardiac outcome in MI. Rats were divided into MI, MI + PM and Sham. Echocardiography and hemodynamic parameters were used to assess cardiac function 8 weeks post-surgery. Total interstitial collagen, collagen I and collagen III were quantified using Sirius Red and polarized light microscopy. PM improved survival following LAD occlusion. Pre-treatment with PM significantly decreased the plasma AGEs levels. MI rats treated with PM displayed reduced left ventricular end-diastolic pressure and tau compared to untreated MI rats. Deformation parameters were also improved with PM. The preserved diastolic function was related to the reduced collagen content, in particular in the highly cross-linked collagen type I, mainly in the peri-infarct region, although not via TGF-β1 pathway. Our data indicate that PM treatment prevents the increase in AGEs levels and reduces collagen levels in a rat model of MI, resulting in an improved cardiac phenotype. As such, therapies targeting formation of AGEs might be beneficial in the prevention and/or treatment of maladaptive remodeling following MI.
晚期糖基化终末产物（AGEs）在心力衰竭的进展中起关键作用。限制 AGEs 形成的治疗方法是否能预防心肌梗死后的不良左心室重构尚不清楚。我们研究了吡哆胺（PM）是否能限制心肌梗死后的不良心脏结局。大鼠分为心肌梗死（MI）组、MI+PM 组和假手术（Sham）组。术后 8 周，通过超声心动图和血流动力学参数评估心功能。采用天狼星红和偏光显微镜定量测定总间质胶原、胶原 I 和胶原 III。PM 可改善 LAD 闭塞后的生存率。PM 的预处理显著降低了血浆 AGEs 水平。与未治疗的 MI 大鼠相比，PM 治疗的 MI 大鼠的左心室舒张末期压力和 tau 降低。PM 还改善了变形参数。保存的舒张功能与胶原含量减少有关，特别是在高交联型胶原 I 中，主要在梗死周围区域，但不通过 TGF-β1 途径。我们的数据表明，PM 治疗可预防大鼠心肌梗死后 AGEs 水平的升高和胶原水平的降低，从而改善心脏表型。因此，针对 AGEs 形成的治疗方法可能有益于预防和/或治疗 MI 后适应性重构。
