Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Japan.
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Am J Physiol Heart Circ Physiol. 2022 Mar 1;322(3):H394-H405. doi: 10.1152/ajpheart.00639.2021. Epub 2022 Jan 28.
As there is cross talk in functions of the heart and kidney, acute or chronic injury in one of the two organs provokes adaptive and/or maladaptive responses in both organs, leading to cardiorenal syndrome (CRS). Acute kidney injury (AKI) induced by acute heart failure is referred to as type 1 CRS, and a frequent cause of this type of CRS is acute myocardial infarction (AMI). Diabetes mellitus increases the risk of AMI and also the risk of AKI of various causes. However, there have been only a few studies in which animal models of diabetes were used to examine how diabetes modulates AMI-induced AKI. In this review, we summarize findings regarding the mechanisms of type 1 CRS and the impact of diabetes on both AMI and renal susceptibility to AKI and we discuss mechanisms by which diabetes modulates AMI-induced AKI. Hemodynamic alterations induced by AMI could be augmented by diabetes via its detrimental effect on infarct size and contractile function of the noninfarcted region in the heart. Diabetes increases susceptibility of renal cells to hypoxia and oxidative stress by modulation of signaling pathways that regulate cell survival and autophagy. Recent studies have shown that diabetes mellitus even at early stage of cardiomyopathy/nephropathy predisposes the kidney to AMI-induced AKI, in which activation of Toll-like receptors and reactive oxygen species derived from NADPH oxidases are involved. Further analysis of cross talk between diabetic cardiomyopathy and diabetic kidney disease is necessary for obtaining a more comprehensive understanding of modulation of the AMI-AKI axis by diabetes.
由于心脏和肾脏的功能存在相互影响，这两个器官中的一个受到急性或慢性损伤会引起两个器官的适应性和/或失代偿性反应，导致心肾综合征（CRS）。急性心力衰竭引起的急性肾损伤（AKI）被称为 1 型 CRS，这种 CRS 的常见原因是急性心肌梗死（AMI）。糖尿病增加了 AMI 的风险，也增加了各种原因导致 AKI 的风险。然而，只有少数研究使用糖尿病动物模型来研究糖尿病如何调节 AMI 引起的 AKI。在这篇综述中，我们总结了 1 型 CRS 的机制以及糖尿病对 AMI 和肾脏对 AKI 的易感性的影响，并讨论了糖尿病调节 AMI 引起的 AKI 的机制。AMI 引起的血流动力学改变可能会因糖尿病对心脏未梗死区梗死面积和收缩功能的不良影响而加剧。糖尿病通过调节细胞存活和自噬的信号通路增加了肾脏细胞对缺氧和氧化应激的敏感性。最近的研究表明，糖尿病甚至在心肌病/肾病的早期阶段就使肾脏易患 AMI 引起的 AKI，其中 Toll 样受体的激活和 NADPH 氧化酶产生的活性氧参与其中。为了更全面地了解糖尿病对 AMI-AKI 轴的调节作用，有必要进一步分析糖尿病性心肌病和糖尿病肾病之间的相互作用。
