Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
J Am Coll Cardiol. 2021 Nov 2;78(18):1782-1795. doi: 10.1016/j.jacc.2021.08.047.
The effects of nonphysiological flow generated by continuous-flow (CF) left ventricular assist devices (LVADs) on the aorta remain poorly understood.
The authors sought to quantify indexes of fibrosis and determine the molecular signature of post-CF-LVAD vascular remodeling.
Paired aortic tissue was collected at CF-LVAD implant and subsequently at transplant from 22 patients. Aortic wall morphometry and fibrillar collagen content (a measure of fibrosis) was quantified. In addition, whole-transcriptome profiling by RNA sequencing and follow-up immunohistochemistry were performed to evaluate CF-LVAD-mediated changes in aortic mRNA and protein expression.
The mean age was 52 ± 12 years, with a mean duration of CF-LVAD of 224 ± 193 days (range 45-798 days). There was a significant increase in the thickness of the collagen-rich adventitial layer from 218 ± 110 μm pre-LVAD to 410 ± 209 μm post-LVAD (P < 0.01). Furthermore, there was an increase in intimal and medial mean fibrillar collagen intensity from 22 ± 11 a.u. pre-LVAD to 41 ± 24 a.u. post-LVAD (P < 0.0001). The magnitude of this increase in fibrosis was greater among patients with longer durations of CF-LVAD support. CF-LVAD led to profound down-regulation in expression of extracellular matrix-degrading enzymes, such as matrix metalloproteinase-19 and ADAMTS4, whereas no evidence of fibroblast activation was noted.
There is aortic remodeling and fibrosis after CF-LVAD that correlates with the duration of support. This fibrosis is due, at least in part, to suppression of extracellular matrix-degrading enzyme expression. Further research is needed to examine the contribution of nonphysiological flow patterns on vascular function and whether modulation of pulsatility may improve vascular remodeling and long-term outcomes.
持续流动（CF）左心室辅助装置（LVAD）产生的非生理流动对主动脉的影响仍知之甚少。
作者试图量化纤维化指标，并确定 CF-LVAD 后血管重塑的分子特征。
从 22 名患者中收集 CF-LVAD 植入时和随后移植时的配对主动脉组织。定量测量主动脉壁形态和纤维胶原含量（纤维化的一种衡量标准）。此外，通过 RNA 测序进行全转录组谱分析，并进行后续免疫组织化学检测，以评估 CF-LVAD 介导的主动脉 mRNA 和蛋白表达变化。
平均年龄为 52 ± 12 岁，CF-LVAD 平均持续时间为 224 ± 193 天（范围 45-798 天）。从 LVAD 前的 218 ± 110 μm 到 LVAD 后的 410 ± 209 μm，富含胶原的外膜层厚度显著增加（P < 0.01）。此外，内膜和中膜的平均纤维胶原强度从 LVAD 前的 22 ± 11 a.u.增加到 LVAD 后的 41 ± 24 a.u.（P < 0.0001）。CF-LVAD 支持时间较长的患者，纤维化的增加幅度更大。CF-LVAD 导致细胞外基质降解酶，如基质金属蛋白酶 19 和 ADAMTS4 的表达显著下调，而未观察到成纤维细胞激活的证据。
CF-LVAD 后主动脉发生重塑和纤维化，与支持时间相关。这种纤维化至少部分是由于细胞外基质降解酶表达的抑制。需要进一步研究以检查非生理流动模式对血管功能的影响，以及脉动性的调节是否可以改善血管重塑和长期预后。
