Heart functional and structural compendium of cardiosplenic and cardiorenal networks in acute and chronic heart failure pathology
Heart functional and structural compendium of cardiosplenic and cardiorenal networks in acute and chronic heart failure pathology
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DOI：
10.1152/ajpheart.00528.2017
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发表时间：
2018-02-01
影响因子：
4.8
通讯作者：
Ingle, Kevin A.
中科院分区：
文献类型：
--
作者：
Halade, Ganesh V.;Kain, Vasundhara;Ingle, Kevin A.
继发于心肌梗死(MI)的心力衰竭(HF)与肾脏并发症有关，这些并发症包括细胞、结构、功能和生存指标。然而，心力衰竭的研究主要集中在左心室(LV)病理上。在这里，我们使用超声心动图对从急性心力衰竭(AHF)到进行性慢性心力衰竭(CHF)病理转变过程中的左室进行了全面的功能分析，并制定了心脾和心肾网络在病理重塑中的组织学纲要。在使用永久性冠状动脉结扎的外科手术诱导的MI中，左心功能障碍显著，伴有心肌坏死、室壁变薄和20-30%的左室破裂事件，这表明C57BL/6雄性小鼠(2-4个月龄，n=50)发生了AHF和CHF的病理重构。时间左心室功能分析显示，与单纯对照组小鼠(n=6)相比，AHF组小鼠左心室短轴缩短率和应变在第1天至第5天减少，第28天至第56天持续进展至CHF。在AHF(第1天到第5天)到晚期CHF(第28天到第56天)的过渡过程中，脾的组织学和细胞变化是明确的，肾脏炎症生物标志物中存在双峰型炎症反应。同样，心肌梗死后，随着心脾和心肾网络的动态变化，左室有单向、渐进性和不可逆的致密胶原沉积。肾脏组织学和损伤标记物表明，心脏损伤触发了不可逆转的失调，积极改变了心脾和心肾网络。总之，在AHF和CHF中调节全面的心脾和心肾网络的新策略或途径将是研究心脏修复或心脏病理学的有效途径。值得注意的是，本概要显示了通过时间超声心动图评估的不可逆心功能障碍，而脾和肾脏的组织学和结构测量为研究心脾和心肾网络在心力衰竭病理中的作用增加了一个新的方向。因此，系统生物学和综合方法的考虑对于开发新的治疗方法是必不可少的。
Heart failure (HF) secondary to myocardial infarction (MI) is linked to kidney complications that comprise cellular, structural, functional, and survival indicators. However, HF research is focused on left ventricular (LV) pathology. Here, we determined comprehensive functional analysis of the LV using echocardiography in transition from acute heart failure (AHF) to progressive chronic heart failure (CHF) pathology and developed a histological compendium of the cardiosplenic and cardiorenal networks in pathological remodeling. In surgically induced MI using permanent coronary ligation, the LV dysfunction is pronounced, with myocardium necrosis, wall thinning, and 20-30% LV rupture events that indicated AHF and CHF pathological remodeling in C57BL/6 male mice (2-4 mo old, n = 50). Temporal LV function analysis indicated that fractional shortening and strain are reduced from day 1 to day 5 in AHF and sustained to advance to CHF from day 28 to day 56 compared with naive control mice (n = 6). During the transition of AHF (day 1 to day 5) to advanced CHF (day 28 to day 56), histological and cellular changes in the spleen were definite, with bimodal inflammatory responses in kidney inflammatory biomarkers. Likewise, there was a unidirectional, progressive, and irreversible deposition of compact collagen in the LV along with dynamic changes in the cardiosplenic and cardiorenal networks post-MI. The renal histology and injury markers suggested that cardiac injury triggers irreversible dysregulation that actively alters the cardiosplenic and cardiorenal networks. In summary, the novel strategies or pathways that modulate comprehensive cardiosplenic and cardiorenal networks in AHF and CHF would be effective approaches to study either cardiac repair or cardiac pathology.NEW & NOTEWORTHY The present compendium shows irreversible ventricular dysfunction as assessed by temporal echocardiography while histological and structural measurements of the spleen and kidney added a novel direction to study cardiosplenic and cardiorenal networks in heart failure pathology. Therefore, the consideration of systems biology and integrative approach is essential to develop novel treatments.