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Right ventricular failure in pulmonary hypertension: recent insights from experimental models

Rechtsherzversagen bei pulmonaler Hypertonie: aktuelle Erkenntnisse aus präklinischen Tiermodellen

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An Erratum to this article was published on 09 May 2023

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Abstract

Right ventricular (RV) function is a critical determinant of the prognosis of patients with pulmonary hypertension (PH). Upon establishment of PH, RV dysfunction develops, leading to a gradual worsening of the condition over time, culminating in RV failure and premature mortality. Despite this understanding, the underlying mechanisms of RV failure remain obscure. As a result, there are currently no approved therapies specifically targeting the right ventricle. One contributing factor to the lack of RV-directed therapies is the complexity of the pathogenesis of RV failure as observed in animal models and clinical studies. In recent years, various research groups have begun utilizing multiple models, including both afterload-dependent and afterload-independent models, to investigate specific targets and pharmacological agents in RV failure. In this review, we examine various animal models of RV failure and the recent advancements made utilizing these models to study the mechanisms of RV failure and the potential efficacy of therapeutic interventions, with the ultimate goal of translating these findings into clinical practice to enhance the management of individuals with PH.

Zusammenfassung

Die Rechtsherzfunktion spielt eine entscheidende Rolle für die Symptomatik und Prognose von Patienten mit pulmonaler Hypertonie (PH). Im Laufe der Erkrankung führt eine progrediente Rechtsherzbelastung zu einer allmählichen Verschlechterung der rechtsventrikulären (RV-)Funktion, die im Rechtsherzversagen und im vorzeitigen Tod der Patienten gipfelt. Trotz dieses grundlegenden pathophysiologischen Verständnisses bleiben die ursächlichen Mechanismen des Rechtsherzversagens unklar. Daher gibt es derzeit keine zugelassenen Therapien für eine zielgerichtete Behandlung des rechten Ventrikels. Ein Faktor, der hierzu beiträgt, ist die Komplexität der Pathogenese des Rechtsherzversagens, die in tierexperimentellen und klinischen Studien beobachtet wurde. In den letzten Jahren haben daher verschiedene Forschungsgruppen begonnen, Tiermodelle zu verwenden, darunter sowohl nachlastabhängige als auch nachlastunabhängige Modelle, um spezifische therapeutisch angehbare Ziele und pharmakologische Wirkstoffe bei Rechtsherzversagen zu untersuchen. In der vorliegenden Übersichtsarbeit werden verschiedene Tiermodelle des Rechtsherzversagens und die aktuellen Fortschritte dargestellt, die unter Verwendung dieser Modelle erzielt wurden, um die Mechanismen des Rechtsherzversagens und die potenzielle Wirksamkeit therapeutischer Interventionen zu untersuchen. Das ultimative Ziel dabei ist es, diese Ergebnisse in die klinische Praxis zu übersetzen, um somit das Management und die Therapie von PH-Patienten zu verbessern.

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Funding

Support: This work was supported by the Excellence Cluster Cardio-Pulmonary System (ECCPS) and the Collaborative Research Center (SFB) 1213—Pulmonary Hypertension and Cor Pulmonale, grant number SFB1213/1, projects A08 and B08 (German Research Foundation, Bonn, Germany).

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Authors and Affiliations

  1. Department of Internal Medicine, Universities of Gießen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University Giessen, Schubertstr. 81, 35392, Gießen, Germany

    Athiththan Yogeswaran, Argen Mamazhakypov, Ralph T. Schermuly & Astrid Weiß PhD

Authors
  1. Athiththan Yogeswaran
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  2. Argen Mamazhakypov
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  3. Ralph T. Schermuly
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  4. Astrid Weiß PhD
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Corresponding author

Correspondence to Astrid Weiß PhD.

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Conflict of interest

A. Weiß, A. Mamazhakypov and R.T. Schermuly declare that they have no competing interests. A. Yogeswaran reports personal fees from MSD outside the submitted work.

For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case.

Additional information

The original online version of this article was revised: Due to an editing error, the authors appeared in the wrong order, correct is: Athiththan Yogeswaran, Argen Mamazhakypov, Ralph T. Schermuly, Astrid Weiß

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Yogeswaran, A., Mamazhakypov, A., Schermuly, R.T. et al. Right ventricular failure in pulmonary hypertension: recent insights from experimental models. Herz 48, 285–290 (2023). https://doi.org/10.1007/s00059-023-05180-8

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