The mitochondria-targeting peptide elamipretide diminishes circulating HtrA2 in ST-segment elevation myocardial infarction

Hortmann, Marcus; Robinson, Samuel D.; Mohr, M.; Mauler, Maximilian; Stallmann, Daniela; Reinöhl, Jochen; Duerschmied, Daniel; Peter, Karlheinz; Carr, James; Gibson, C. Michael; Bode, Christoph; Ahrens, Ingo

doi:10.1177/2048872617710789

Cited by 17 publications

(3 citation statements)

References 20 publications

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“…Targeting mitochondrial oxidative stress with a peptide (e.g., Bendavia, a.k.a. SS-31, MTP-131, or elamipretide) that prevents cardiolipin oxidation 14 improves outcomes in animal models of ischemia-reperfusion injury 15 or pressure-overload HF 16 , but it is still unclear whether it is effective in humans 17–19 . The clinical effectiveness of MitoQ, a targeted form of ubiquinone, in heart failure also remains to be determined 20 .…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure

Dey

DeMazumder

Sidor

et al. 2018

Circulation Research

204

159

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mROS drive both acute emergent events, such as electrical instability responsible for SCD, and those that mediate chronic HF remodeling, characterized by suppression or altered phosphorylation of metabolic, antioxidant, and ion transport protein networks. In vivo reduction of mROS prevents and reverses electrical instability, SCD, and HF. Our findings support the feasibility of targeting the mitochondria as a potential new therapy for HF and SCD while identifying new mROS-sensitive protein modifications.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure

Dey

DeMazumder

Sidor

et al. 2018

Circulation Research

204

159

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“…However, mitochondria-targeting peptide elamipretide reduced HtrA2 in STEMI patients through the retention of mitochondria by interaction with cardiolipin on the inner mitochondrial membrane. Therefore, the detection of HtrA2 in serum could be used as a biomarker for mitochondrial-induced cardiomyocyte apoptosis in patients with STEMI [ 82 ]. Moreover, the myocardium is exposed to ischemia–reperfusion injury during open-heart surgery.…”

Section: Proposed Mhi or Bhi Alterationsmentioning

confidence: 99%

Mitochondrial health quality control: measurements and interpretation in the framework of predictive, preventive, and personalized medicine

et al. 2022

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Mitochondria are the “gatekeeper” in a wide range of cellular functions, signaling events, cell homeostasis, proliferation, and apoptosis. Consequently, mitochondrial injury is linked to systemic effects compromising multi-organ functionality. Although mitochondrial stress is common for many pathomechanisms, individual outcomes differ significantly comprising a spectrum of associated pathologies and their severity grade. Consequently, a highly ambitious task in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM/3PM) is to distinguish between individual disease predisposition and progression under circumstances, resulting in compromised mitochondrial health followed by mitigating measures tailored to the individualized patient profile. For the successful implementation of PPPM concepts, robust parameters are essential to quantify mitochondrial health sustainability. The current article analyses added value of Mitochondrial Health Index (MHI) and Bioenergetic Health Index (BHI) as potential systems to quantify mitochondrial health relevant for the disease development and its severity grade. Based on the pathomechanisms related to the compromised mitochondrial health and in the context of primary, secondary, and tertiary care, a broad spectrum of conditions can significantly benefit from robust quantification systems using MHI/BHI as a prototype to be further improved. Following health conditions can benefit from that: planned pregnancies (improved outcomes for mother and offspring health), suboptimal health conditions with reversible health damage, suboptimal life-style patterns and metabolic syndrome(s) predisposition, multi-factorial stress conditions, genotoxic environment, ischemic stroke of unclear aetiology, phenotypic predisposition to aggressive cancer subtypes, pathologies associated with premature aging and neuro/degeneration, acute infectious diseases such as COVID-19 pandemics, among others.

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“…Together, these studies show that inhibiting HtrA2 may be a therapeutic approach to ameliorate cardiac dysfunction in ischemic HF. Furthermore, HtrA2 may be a potential biomarker for the identification of ischemia/reperfusion injury because the levels of Htra2 in blood serum are significantly increased in mice with myocardial ischemia/reperfusion injury and also in human patients with ST-segment elevation myocardial infarction (Hortmann et al, 2019).…”

Section: Htra2 In Heart Failurementioning

confidence: 99%

Mitochondrial Chaperones and Proteases in Cardiomyocytes and Heart Failure

Chen

Huang

Tso

et al. 2021

Front. Mol. Biosci.

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Heart failure is one of the leading causes of morbidity and mortality worldwide. In cardiomyocytes, mitochondria are not only essential organelles providing more than 90% of the ATP necessary for contraction, but they also play critical roles in regulating intracellular Ca2+ signaling, lipid metabolism, production of reactive oxygen species (ROS), and apoptosis. Because mitochondrial DNA only encodes 13 proteins, most mitochondrial proteins are nuclear DNA-encoded, synthesized, and transported from the cytoplasm, refolded in the matrix to function alone or as a part of a complex, and degraded if damaged or incorrectly folded. Mitochondria possess a set of endogenous chaperones and proteases to maintain mitochondrial protein homeostasis. Perturbation of mitochondrial protein homeostasis usually precedes disruption of the whole mitochondrial quality control system and is recognized as one of the hallmarks of cardiomyocyte dysfunction and death. In this review, we focus on mitochondrial chaperones and proteases and summarize recent advances in understanding how these proteins are involved in the initiation and progression of heart failure.

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The mitochondria-targeting peptide elamipretide diminishes circulating HtrA2 in ST-segment elevation myocardial infarction

Cited by 17 publications

References 20 publications

Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure

Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure

Mitochondrial health quality control: measurements and interpretation in the framework of predictive, preventive, and personalized medicine

Mitochondrial Chaperones and Proteases in Cardiomyocytes and Heart Failure

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