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Cardiac mechanics in response to proteasome inhibition: a prospective study

Ubiquitin-Proteasome System (UPS) is of paramount importance regarding the function of the myocardial cell. Consistently, inhibition of this system has been found to affect myocardium in experimental models; yet, the clinical impact of UPS inhibition on cardiac function has not been comprehensively...

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Main Authors: Makris, Nikolaos (Author) , Georgiopoulos, Georgios (Author) , Laina, Aggeliki (Author) , Tselegkidi, Maria-Eirini (Author) , Fotiou, Despoina (Author) , Kanellias, Nikolaos (Author) , Eleftherakis-Papaiakovou, Evaggelos (Author) , Migkou, Magda (Author) , Papanagnou, Eleni-Dimitra (Author) , Katogiannis, Konstantinos (Author) , Petropoulos, Ioannis (Author) , Anninos, Hector (Author) , Bampatsias, Dimitrios (Author) , Maneta, Eleni (Author) , Samouilidou, Elisabeth (Author) , Nikas, Dimitris (Author) , Ciliberti, Giorgia (Author) , Stellos, Konstantinos (Author) , Terpos, Evaggelos (Author) , Gavriatopoulou, Maria (Author) , Trougakos, Ioannis P (Author) , Ikonomidis, Ignatios (Author) , Dimopoulos, Meletios-Athanasios (Author) , Kastritis, Efstathios (Author) , Stamatelopoulos, Kimon (Author)
Format: Article (Journal)
Language:English
Published: May 2023
In: European heart journal - cardiovascular imaging
Year: 2023, Volume: 24, Issue: 5, Pages: 643-652
ISSN:2047-2412
DOI:10.1093/ehjci/jeac168
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/ehjci/jeac168
Verlag, lizenzpflichtig, Volltext: https://academic.oup.com/ehjcimaging/article/24/5/643/6671411?login=true
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Author Notes:Nikolaos Makris, Georgios Georgiopoulos, Aggeliki Laina, Maria-Eirini Tselegkidi, Despoina Fotiou, Nikolaos Kanellias, Evaggelos Eleftherakis-Papaiakovou, Magda Migkou, Eleni-Dimitra Papanagnou, Konstantinos Katogiannis, Ioannis Petropoulos, Hector Anninos, Dimitrios Bampatsias, Eleni Maneta, Elisabeth Samouilidou, Dimitris Nikas, Giorgia Ciliberti, Konstantinos Stellos, Evaggelos Terpos, Maria Gavriatopoulou, Ioannis P. Trougakos, Ignatios Ikonomidis, Meletios-Athanasios Dimopoulos, Efstathios Kastritis, and Kimon Stamatelopoulos
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Summary:Ubiquitin-Proteasome System (UPS) is of paramount importance regarding the function of the myocardial cell. Consistently, inhibition of this system has been found to affect myocardium in experimental models; yet, the clinical impact of UPS inhibition on cardiac function has not been comprehensively examined. Our aim was to gain insight into the effect of proteasome inhibition on myocardial mechanics in humans.We prospectively evaluated 48 patients with multiple myeloma and an indication to receive carfilzomib, an irreversible proteasome inhibitor. All patients were initially evaluated and underwent echocardiography with speckle tracking analysis. Carfilzomib was administered according to Kd treatment protocol. Follow-up echocardiography was performed at the 3rd and 6th month. Proteasome activity (PrA) was measured in peripheral blood mononuclear cells.At 3 months after treatment, we observed early left ventricular (LV) segmental dysfunction and deterioration of left atrial (LA) remodelling, which was sustained and more pronounced than that observed in a cardiotoxicity control group. At 6 months, LV and right ventricular functions were additionally attenuated (P < 0.05 for all). These changes were independent of blood pressure, endothelial function, inflammation, and cardiac injury levels. Changes in PrA were associated with changes in global longitudinal strain (GLS), segmental LV strain, and LA markers (P < 0.05 for all). Finally, baseline GLS < −18% or LA strain rate > 1.71 were associated with null hypertension events.Inhibition of the UPS induced global deterioration of cardiac function.
Item Description:Online veröffentlicht: 18. August 2022
Gesehen am 08.07.2024
Physical Description:Online Resource
ISSN:2047-2412
DOI:10.1093/ehjci/jeac168

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