Epigenetics, inflammation and metabolism in right heart failure associated with pulmonary hypertension

Samson, Nolwenn; Paulin, Roxane

doi:10.1177/2045893217714463

Cited by 16 publications

(10 citation statements)

References 211 publications

(292 reference statements)

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“…98 The differential expression of these miRNAs causes loss of genes that promote cell growth, function, and angiogenesis. 94 miR-34a, miR-28, miR-93, and miR-148a, which are expressed in non-cardiac cells, act via paracrine pathways to increase oxidative stress, reduce oxidative defense, decrease angiogenesis, and activate cell death pathways, thus promoting transition to RVF. 6 However, these findings only establish an association between these miRNAs and the development of RVF.…”

Section: Right Ventricular Failurementioning

confidence: 99%

“…BNP, B-type natriuretic peptide; ETC, electron transport chain; HIF-1a, hypoxia-inducible factor 1a; IGF, insulin-like growth factor; miRNA, microRNA; NT-proBNP, N-terminal pro b-type natriuretic peptide; PDE5, phosphodiesterase-5; PDK, pyruvate dehydrogenase kinase; PKG, protein kinase G; ROS, reactive oxygen species; TGF-b1, transforming growth factor beta 1; VEGF, vascular endothelial growth factor. 6,73,94,98,124,125 (miR)-126 has also been shown to decrease RV angiogenesis and capillary density to promote RVF. 73 Patients with systemic sclerosis are predisposed to RVF because they have endothelial injury and impaired angiogenesis, which causes RV ischemia.…”

Section: Rv Ischemiamentioning

confidence: 99%

“…Inflammatory mediators such as cytokines (tumor necrosis factor [TNF]-a, interleukins) and toll-like receptors are suspected to contribute to RVF because of their known effect in left heart failure. 94 Table 1 lists these mediators and their possible modes of action in RVF. Although these inflammatory responses have been studied in LVF, most have not been well studied in RVF.…”

Section: Inflammation Fibrosis and Apoptosismentioning

confidence: 99%

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Right heart in pulmonary hypertension: from adaptation to failure

Ren¹,

Johns

Gao

2019

Pulm. circ.

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Right ventricular (RV) failure (RVF) has garnered significant attention in recent years because of its negative impact on clinical outcomes in patients with pulmonary hypertension (PH). PH triggers a series of events, including activation of several signaling pathways that regulate cell growth, metabolism, extracellular matrix remodeling, and energy production. These processes render the RV adaptive to PH. However, RVF develops when PH persists, accompanied by RV ischemia, alterations in substrate and mitochondrial energy metabolism, increased free oxygen radicals, increased cell loss, downregulation of adrenergic receptors, increased inflammation and fibrosis, and pathologic microRNAs. Diastolic dysfunction is also an integral part of RVF. Emerging non-invasive technologies such as molecular or metallic imaging, cardiac MRI, and ultrafast Doppler coronary flow mapping will be valuable tools to monitor RVF, especially the transition to RVF. Most PH therapies cannot treat RVF once it has occurred. A variety of therapies are available to treat acute and chronic RVF, but they are mainly supportive, and no effective therapy directly targets the failing RV. Therapies that target cell growth, cellular metabolism, oxidative stress, and myocyte regeneration are being tested preclinically. Future research should include establishing novel RVF models based on existing models, increasing use of human samples, creating human stem cell-based in vitro models, and characterizing alterations in cardiac excitation–contraction coupling during transition from adaptive RV to RVF. More successful strategies to manage RVF will likely be developed as we learn more about the transition from adaptive remodeling to maladaptive RVF in the future.

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Section: Right Ventricular Failurementioning

confidence: 99%

Section: Rv Ischemiamentioning

confidence: 99%

Section: Inflammation Fibrosis and Apoptosismentioning

confidence: 99%

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Right heart in pulmonary hypertension: from adaptation to failure

Ren¹,

Johns

Gao

2019

Pulm. circ.

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“…Glucose uptake is increased by the upregulation of glucose transporter 1 (Glut1). This metabolic shift is initially beneficial, as it reduces ROS and increases angiogenesis via the HIF1α/VEGF axis [ 15 , 24 ]. c-Myc activation increases glutaminolysis, which is characteristic of cancer metabolism [ 25 ].…”

Section: Main Textmentioning

confidence: 99%

The role of regenerative therapy in the treatment of right ventricular failure: a literature review

2020

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Right ventricular (RV) failure is a commonly encountered problem in patients with congenital heart disease but can also be a consequence of left ventricular disease, primary pulmonary hypertension, or RV-specific cardiomyopathies. Improved survival of the aforementioned pathologies has led to increasing numbers of patients suffering from RV dysfunction, making it a key contributor to morbidity and mortality in this population. Currently available therapies for heart failure were developed for the left ventricle (LV), and there is clear evidence that LV-specific strategies are insufficient or inadequate for the RV. New therapeutic strategies are needed to address this growing clinical problem, and stem cells show significant promise. However, to properly evaluate the prospects of a potential stem cell-based therapy for RV failure, one needs to understand the unique pathophysiology of RV dysfunction and carefully consider available data from animal models and human clinical trials. In this review, we provide a comprehensive overview of the molecular mechanisms involved in RV failure such as hypertrophy, fibrosis, inflammation, changes in energy metabolism, calcium handling, decreasing RV contractility, and apoptosis. We also summarize the available preclinical and clinical experience with RV-specific stem cell therapies, covering the broad spectrum of stem cell sources used to date. We describe two different scientific rationales for stem cell transplantation, one of which seeks to add contractile units to the failing myocardium, while the other aims to augment endogenous repair mechanisms and/or attenuate harmful remodeling. We emphasize the limitations and challenges of regenerative strategies, but also highlight the characteristics of the failing RV myocardium that make it a promising target for stem cell therapy.

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“…Right ventricular failure (RVF) is the most important prognostic factor for both morbidity and mortality in patients with pulmonary arterial hypertension (PAH). 1 When PAH patients suffer from pulmonary infection or puerperal infection heart failure often rapidly develops. 2 To date, unlike research on left heart failure, research on RVF is insufficient.…”

Section: Introductionmentioning

confidence: 99%