Review on Chamber-Specific Differences in Right and Left Heart Reactive Oxygen Species Handling

Schlüter, Klaus‐Dieter; Kutsche, Hanna Sarah; Hirschhäuser, Christine; Schreckenberg, Rolf; Schulz, Rainer

doi:10.3389/fphys.2018.01799

Cited by 28 publications

(29 citation statements)

References 131 publications

(154 reference statements)

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“…On the contrary, when Sirtuin-3 knockout mice were exposed to chronic hypoxia, they developed PH and RV hypertrophy that was indistinguishable from those in wildtype littermates [44]. Several studies demonstrated that LV and RV differ in the expression profiles of genes and proteins, suggesting that these differences may generate specific molecular patterns with relevance to their pathophysiology [13,15,16,33,36,43] and thus responses to therapies [4,11,23,45]. We speculate that the responsiveness of FHL-1 to stress signals could be influenced by other proteins that differ between LV and RV.…”

Section: Discussionmentioning

confidence: 99%

FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction

et al. 2020

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Aims The cytoskeletal signaling protein four and-a-half LIM domains 1 (FHL-1) has recently been identified as a novel key player in pulmonary hypertension as well as in left heart diseases. In this regard, FHL-1 has been implicated in dysregulated hypertrophic signaling in pulmonary arterial smooth muscle cells leading to pulmonary hypertension. In mice, FHL-1-deficiency (FHL-1 −/− ) led to an attenuated hypertrophic signaling associated with a blunted hypertrophic response of the pressure-overloaded left ventricle (LV). However, the role of FHL-1 in right heart hypertrophy has not yet been addressed. Methods and resultsWe investigated FHL-1 expression in C57Bl/6 mice subjected to chronic biomechanical stress and found it to be enhanced in the right ventricle (RV). Next, we subjected FHL-1 −/− and corresponding wild-type mice to pressure overload of the RV by pulmonary arterial banding for various time points. However, in contrast to the previously published study in LV-pressure overload, which was confirmed here, RV hypertrophy and hypertrophic signaling was not diminished in FHL-1 −/− mice. In detail, right ventricular pressure overload led to hypertrophy, dilatation and fibrosis of the RV from both FHL-1 −/− and wild-type mice. RV remodeling was associated with impaired RV function as evidenced by reduced tricuspid annular plane systolic excursion. Additionally, PAB induced upregulation of natriuretic peptides and slight downregulation of phospholamban and ryanodine receptor 2 in the RV. However, there was no difference between genotypes in the degree of expression change. Conclusion FHL-1 pathway is not involved in the control of adverse remodeling in the pressure overloaded RV.

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Section: Discussionmentioning

confidence: 99%

FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction

et al. 2020

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“…This difference to LV tissue is due to a stronger induction of fibrosis, triggered by collagen III, lack of effect on cardiomyocytes and (Schluter et al, 2018) Rat, L-NAME, 4 weeks ROS in RV " (Schreckenberg et al, 2015) Wild-type and NOS2-deficient mice, PAB, 3 weeks…”

Section: Exercise-dependent Preconditioning Of the Rvmentioning

confidence: 99%

Cardioprotection in right heart failure

Boengler

Schlüter

Schermuly

et al. 2020

British J Pharmacology

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Ischaemic and pharmacological conditioning of the left ventricle is mediated by the activation of signalling cascades, which finally converge at the mitochondria and reduce ischaemia/reperfusion (I/R) injury. Whereas the molecular mechanisms of conditioning in the left ventricle are well characterized, cardioprotection of the right ventricle is principally feasible but less established. Similar to what is known for the left ventricle, a dysregulation in signalling pathways seems to play a role in I/R injury of the healthy and failing right ventricle and in the ability/inability of the right ventricle to respond to a conditioning stimulus. The maintenance of mitochondrial function seems to be crucial in both ventricles to reduce I/R injury. As far as currently known, similar molecular mechanisms mediate ischaemic and pharmacological preconditioning in the left and right ventricles. However, the two ventricles seem to respond differently towards exercise‐induced preconditioning.LINKED ARTICLESThis article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc

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“…In the specific case of ACM, this hypothesis has not been tested yet, though it is tempting to speculate that metabolic and mitochondrial dysfunction can serve as substrates for electrical and structural changes in ACM patients. Especially since previous studies have indicated differences in mitochondrial metabolism between the left ventricle (LV) and right ventricle (RV) in the heart and ACM is regarded a (right) chamber specific disease (Schlüter et al, 2018). In this review, we describe the mitochondrial (patho)physiology, the link between mitochondrial dysfunction and development of cardiac arrhythmias and explore a potential relation between mitochondrial dysfunction and typical hallmarks of ACM.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms

et al. 2019

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Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease, associated with ventricular arrhythmias, fibrofatty replacement of the myocardial mass and an increased risk of sudden cardiac death (SCD). Malignant ventricular arrhythmias and SCD largely occur in the pre-clinical phase of the disease, before overt structural changes occur. To prevent or interfere with ACM disease progression, more insight in mechanisms related to electrical instability are needed. Currently, numerous studies are focused on the link between cardiac arrhythmias and metabolic disease. In line with that, a potential role of mitochondrial dysfunction in ACM pathology is unclear and mitochondrial biology in the ACM heart remains understudied. In this review, we explore mitochondrial dysfunction in relation to arrhythmogenesis, and postulate a link to typical hallmarks of ACM. Mitochondrial dysfunction depletes adenosine triphosphate (ATP) production and increases levels of reactive oxygen species in the heart. Both metabolic changes affect cardiac ion channel gating, electrical conduction, intracellular calcium handling, and fibrosis formation; all well-known aspects of ACM pathophysiology. ATP-mediated structural remodeling, apoptosis, and mitochondria-related alterations have already been shown in models of PKP2 dysfunction. Yet, the limited amount of experimental evidence in ACM models makes it difficult to determine whether mitochondrial dysfunction indeed precedes and/or accompanies ACM pathogenesis. Nevertheless, current experimental ACM models can be very useful in unraveling ACM-related mitochondrial biology and in testing potential therapeutic interventions.

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Review on Chamber-Specific Differences in Right and Left Heart Reactive Oxygen Species Handling

Cited by 28 publications

References 131 publications

FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction

FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction

Cardioprotection in right heart failure

Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms

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