Chronic kidney disease (CKD) predisposes to cardiac remodeling and coronary microvascular dysfunction. Studies in swine identified changes in microvascular structure and function, as well as changes in mitochondrial structure and oxidative stress. However, CKD was combined with metabolic derangement, thereby obscuring the contribution of CKD alone. Therefore, we studied the impact of CKD on the heart and combined proteome studies with measurement of cardiac function and perfusion to identify processes involved in cardiac remodeling in CKD. CKD was induced in swine at 10–12 weeks of age while sham-operated swine served as controls. 5–6 months later, left ventricular (LV) function and coronary flow reserve were measured. LC–MS–MS-based proteomic analysis of LV tissue was performed. LV myocardium and kidneys were histologically examined for interstitial fibrosis and oxidative stress. Renal embolization resulted in mild chronic kidney injury (increased fibrosis and urinary NGAL). PV loops showed LV dilation and increased wall stress, while preload recruitable stroke work was impaired in CKD. Quantitative proteomic analysis of LV myocardium and STRING pre-ranked functional analysis showed enrichments in pathways related to contractile function, reactive oxygen species, and extracellular matrix (ECM) remodeling, which were confirmed histologically and associated with impaired total anti-oxidant capacity. H₂O₂ exposure of myocardial slices from CKD, but not normal swine, impaired contractile function. Furthermore, in CKD, mitochondrial proteins were downregulated suggesting mitochondrial dysfunction which was associated with higher basal coronary blood flow. Thus, mild CKD induces alterations in mitochondrial proteins along with contractile proteins, oxidative stress and ECM remodeling, that were associated with changes in cardiac function and perfusion.

慢性肾脏病 （CKD） 易导致心脏重塑和冠状动脉微血管功能障碍。对猪的研究发现了微血管结构和功能的变化，以及线粒体结构和氧化应激的变化。然而，CKD 与代谢紊乱相结合，从而掩盖了 CKD 单独的作用。因此，我们研究了 CKD 对心脏的影响，并将蛋白质组研究与心脏功能和灌注测量相结合，以确定 CKD 中涉及心脏重塑的过程。在 10-12 周龄时在猪中诱导 CKD，而假手术猪作为对照。5-6 个月后，测量左心室 （LV） 功能和冠状动脉血流储备。对 LV 组织进行基于 LC-MS-MS 的蛋白质组学分析。组织学检查左心室心肌和肾脏有无间质纤维化和氧化应激。肾栓塞导致轻度慢性肾损伤 （纤维化增加和尿 NGAL）。PV 环显示 LV 扩张和壁应力增加，而 CKD 患者的前负荷可复张卒中功受损。LV 心肌的定量蛋白质组学分析和 STRING 预排序功能分析显示与收缩功能、活性氧和细胞外基质 （ECM） 重塑相关的通路富集，这在组织学上得到证实，并与总抗氧化能力受损有关。CKD 心肌切片的 H₂O₂ 暴露，但正常猪没有暴露，收缩功能受损。此外，在 CKD 中，线粒体蛋白下调，表明线粒体功能障碍与较高的基础冠状动脉血流量有关。 因此，轻度 CKD 诱导线粒体蛋白以及收缩蛋白、氧化应激和 ECM 重塑的改变，这与心脏功能和灌注的变化有关。