Pro-oxidative priming but maintained cardiac function in a broad spectrum of murine models of chronic kidney disease

Wollenhaupt, Julia; Frisch, Janina; Harlacher, Eva; Wong, Dickson W.L.; Jin, Han; Schulte, C.; Vondenhoff, Sonja; Moellmann, Julia; Klinkhammer, Barbara M.; Zhang, Li; Baleanu-Curaj, Adelina; Liehn, Elisa A.; Speer, Thimoteus; Kazakov, Andrey; Werner, Christian; Vorst, Emiel P. C. van der; Selejan, Simina; Hohl, Mathias; Böhm, Michael; Kramann, Rafael; Biessen, Erik A.L.; Lehrke, Michael; Jankowski, Joachim; Maack, Christoph; Roma, Letícia Prates; Noels, Heidi

doi:10.1016/j.redox.2022.102459

Cited by 7 publications

(4 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mito-roGFP2-Orp1 crossbreed with shTaz mice (MiOxTaz mice) were sacrificed via 2:1 Ketamin/Rompun (1 g/kg Ketavet ® / 100 mg/kg Rompun ® ) injection. Redox histology was performed as previously described with some modifications (23, 33). First, cardiac perfusion with 25 ml of 50 mM N-Ethylmaleimide (NEM) diluted in PBS was used to block free thiols and prevent artificial sensor oxidation.…”

Section: Methodsmentioning

confidence: 99%

Pancreatic islets undergo functional and morphological adaptation during development of Barth Syndrome

Carlein,

Hoffmann,

Amaral

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Barth syndrome is a multisystem genetic disorder caused by mutation inTAFAZZIN, a gene that encodes a phospholipid:lysophospholipid transacylase important for cardiolipin remodeling. Barth Syndrome patients suffer from a number of symptoms including early heart failure, fatigue, and systemic metabolic alterations, including hypoglycemia. The endocrine pancreas is central to glucose homeostasis, however, the impact of defective cardiolipin remodeling on pancreatic islet function and the consequences for systemic metabolism is unclear. Surprisingly, in a mouse model with globalTAFAZZINknockdown, we observed improved glucose tolerance compared to wildtype littermates. We show that pancreatic islet metabolism and secretory function are robustly maintained through various compensatory mechanisms including increased glucose uptake and increased mitochondrial volume. Transcriptomics analyses revealed increased expression of genes encoding proteins involved in N-acetylglucosamine synthesis and proteinO-linked N-acetylglucosaminylation. These pathways might provide a molecular mechanism for coupling metabolic changes to mitochondrial volume regulation.

show abstract

Section: Methodsmentioning

confidence: 99%

Pancreatic islets undergo functional and morphological adaptation during development of Barth Syndrome

Carlein,

Hoffmann,

Amaral

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…When CKD was induced via adenine diet or oxalate treatment in C57BL/6 mice (nine studies in total), cardiac pathophysiological effects were more variable than after SNX, showing significant changes only in 30%–70% of the studies for the cardiac parameters summarized in this review. Although our previous systematic review reported a consistent increase of cardiac effects among diet- and treatment-induced CKD models in C57BL/6 mice [ 12 ], these variable results following inclusion of recent literature are mainly caused by our latest findings with primarily neutral effects of different adenine diet–induced CKD models on cardiac morphology and function [ 158 ]. Variable observations of the effect of adenine diet on the heart might, amongst other factors, be due to high protocol variability, including, e.g.…”

Section: Animal Models To Study Uremic Cardiomyopathy: Overview and C...mentioning

confidence: 99%

Cardiomyopathy in chronic kidney disease: clinical features, biomarkers and the contribution of murine models in understanding pathophysiology

Junho

Frisch

Soppert

et al. 2023

Clinical Kidney Journal

Self Cite

View full text Add to dashboard Cite

The cardiorenal syndrome (CRS) is described as a multi-organ disease encompassing bidirectionally heart and kidney. In CRS type 4, chronic kidney disease (CKD) leads to cardiac injury. Different pathological mechanisms have been identified to contribute to the establishment of CKD-induced cardiomyopathy, including a neurohormonal dysregulation, disturbances in the mineral metabolism and an accumulation of uremic toxins, playing an important role in the development of inflammation and oxidative stress. Combined, this leads to cardiac dysfunction and cardiac pathophysiological and morphological changes, like left ventricular hypertrophy, myocardial fibrosis and cardiac electrical changes. Given that around 80% of dialysis patients suffer from uremic cardiomyopathy, the study of cardiac outcomes in CKD is clinically highly relevant. The present review summarizes clinical features and biomarkers of CKD-induced cardiomyopathy and discusses underlying pathophysiological mechanisms recently uncovered in the literature. It discloses how animal models have contributed to the understanding of pathological kidney-heart crosstalk, but also provides insights into the variability in observed effects of CKD on the heart in different CKD mouse models, covering both ‘single hit’ as well as ‘multifactorial hit’ models. Overall, this review aims to support research progress in the field of CKD-induced cardiomyopathy.

show abstract

“…However, the extent to which oxidative stress contributes to structural and functional abnormalities in the uremic heart remains elusive. A recent study by Wollenhaupt et al 204 addressed this question. They found that CKD following nephrectomy in various mouse strains increased oxidative stress responses in the heart without affecting hypertrophy, interstitial fibrosis, and diastolic or systolic function.…”

Section: Compendium On Increased Risk Of Cardiovascular Complications...mentioning

confidence: 99%

“…Irrespective of the mechanisms of mitochondrial dysfunction, because mitochondria are a major source of ROS, 202,203 it is tempting to assume that the increased ROS production and oxidative stress observed in models of UC 204 partly result from mitochondrial dysfunction. As mentioned in the first section, another important source of ROS in the heart is NOX, whose expression is potently induced by angiotensin II leading to oxidative stress and inflammation.…”

Section: Cardiac Metabolism In Ucmentioning

confidence: 99%

Cardiac Metabolism in Heart Failure and Implications for Uremic Cardiomyopathy

Nguyễn

Schulze

2023

Circulation Research

View full text Add to dashboard Cite

Chronic kidney disease is associated with an increased risk for the development and progression of cardiovascular disorders including hypertension, dyslipidemia, and coronary artery disease. Chronic kidney disease may also affect the myocardium through complex systemic changes, resulting in structural remodeling such as hypertrophy and fibrosis, as well as impairments in both diastolic and systolic function. These cardiac changes in the setting of chronic kidney disease define a specific cardiomyopathic phenotype known as uremic cardiomyopathy. Cardiac function is tightly linked to its metabolism, and research over the past 3 decades has revealed significant metabolic remodeling in the myocardium during the development of heart failure. Because the concept of uremic cardiomyopathy has only been recognized in recent years, there are limited data on metabolism in the uremic heart. Nonetheless, recent findings suggest overlapping mechanisms with heart failure. This work reviews key features of metabolic remodeling in the failing heart in the general population and extends this to patients with chronic kidney disease. The knowledge of similarities and differences in cardiac metabolism between heart failure and uremic cardiomyopathy may help identify new targets for mechanistic and therapeutic research on uremic cardiomyopathy.

show abstract

Pro-oxidative priming but maintained cardiac function in a broad spectrum of murine models of chronic kidney disease

Cited by 7 publications

References 54 publications

Pancreatic islets undergo functional and morphological adaptation during development of Barth Syndrome

Pancreatic islets undergo functional and morphological adaptation during development of Barth Syndrome

Cardiomyopathy in chronic kidney disease: clinical features, biomarkers and the contribution of murine models in understanding pathophysiology

Cardiac Metabolism in Heart Failure and Implications for Uremic Cardiomyopathy

Contact Info

Product

Resources

About