Apolipoprotein M Attenuates Anthracycline Cardiotoxicity and Lysosomal Injury

Zhen Guo; Carla Valenzuela Ripoll; Antonino Picataggi; David Rawnsley; Mualla Ozcan; Julio A. Chirinos; Ezhilarasi Chendamarai; Amanda Girardi; Terrence Riehl; Hosannah Evie; Ahmed Diab; Attila Kovacs; Krzysztof Hyrc; Xiucui Ma; Aarti Asnani; Swapnil V. Shewale; Marielle Scherrer-Crosbie; Lauren Ashley Cowart; John S. Parks; Lei Zhao; David Gordon; Francisco Ramirez-Valle; Kenneth B. Margulies; Thomas P. Cappola; Ankit A. Desai; Lauren N. Pedersen; Carmen Bergom; Nathan Stitziel; Michael Rettig; John Dipersio; Stefan Hajny; Christina Christoffersen; Abhinav Diwan; Ali Javaheri

doi:10.1016/j.jacbts.2022.09.010

Apolipoprotein M Attenuates Anthracycline Cardiotoxicity and Lysosomal Injury

Zhen Guo, Carla Valenzuela Ripoll, Antonino Picataggi, David Rawnsley, Mualla Ozcan, Julio A. Chirinos, Ezhilarasi Chendamarai, Amanda Girardi, Terrence Riehl, Hosannah Evie, Ahmed Diab, Attila Kovacs, Krzysztof Hyrc, Xiucui Ma, Aarti Asnani, Swapnil V. Shewale, Marielle Scherrer-Crosbie, Lauren Ashley Cowart, John S. Parks, Lei ZhaoDavid Gordon, Francisco Ramirez-Valle, Kenneth B. Margulies, Thomas P. Cappola, Ankit A. Desai, Lauren N. Pedersen, Carmen Bergom, Nathan Stitziel, Michael Rettig, John Dipersio, Stefan Hajny, Christina Christoffersen, Abhinav Diwan, Ali Javaheri

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Apolipoprotein M (ApoM) binds sphingosine-1-phosphate (S1P) and is inversely associated with mortality in human heart failure (HF). Here, we show that anthracyclines such as doxorubicin (Dox) reduce circulating ApoM in mice and humans, that ApoM is inversely associated with mortality in patients with anthracycline-induced heart failure, and ApoM heterozygosity in mice increases Dox-induced mortality. In the setting of Dox stress, our studies suggest ApoM can help sustain myocardial autophagic flux in a post-transcriptional manner, attenuate Dox cardiotoxicity, and prevent lysosomal injury.

Original language	English
Pages (from-to)	340-355
Number of pages	16
Journal	JACC: Basic to Translational Science
Volume	8
Issue number	3
DOIs	https://doi.org/10.1016/j.jacbts.2022.09.010
State	Published - Mar 2023

Keywords

TFEB
anthracycline
apolipoprotein M
autophagy
cardiomyopathy

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Guo, Z., Valenzuela Ripoll, C., Picataggi, A., Rawnsley, D., Ozcan, M., Chirinos, J. A., Chendamarai, E., Girardi, A., Riehl, T., Evie, H., Diab, A., Kovacs, A., Hyrc, K., Ma, X., Asnani, A., Shewale, S. V., Scherrer-Crosbie, M., Cowart, L. A., Parks, J. S., ... Javaheri, A. (2023). Apolipoprotein M Attenuates Anthracycline Cardiotoxicity and Lysosomal Injury. JACC: Basic to Translational Science, 8(3), 340-355. https://doi.org/10.1016/j.jacbts.2022.09.010

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title = "Apolipoprotein M Attenuates Anthracycline Cardiotoxicity and Lysosomal Injury",

abstract = "Apolipoprotein M (ApoM) binds sphingosine-1-phosphate (S1P) and is inversely associated with mortality in human heart failure (HF). Here, we show that anthracyclines such as doxorubicin (Dox) reduce circulating ApoM in mice and humans, that ApoM is inversely associated with mortality in patients with anthracycline-induced heart failure, and ApoM heterozygosity in mice increases Dox-induced mortality. In the setting of Dox stress, our studies suggest ApoM can help sustain myocardial autophagic flux in a post-transcriptional manner, attenuate Dox cardiotoxicity, and prevent lysosomal injury.",

keywords = "TFEB, anthracycline, apolipoprotein M, autophagy, cardiomyopathy",

author = "Zhen Guo and {Valenzuela Ripoll}, Carla and Antonino Picataggi and David Rawnsley and Mualla Ozcan and Chirinos, {Julio A.} and Ezhilarasi Chendamarai and Amanda Girardi and Terrence Riehl and Hosannah Evie and Ahmed Diab and Attila Kovacs and Krzysztof Hyrc and Xiucui Ma and Aarti Asnani and Shewale, {Swapnil V.} and Marielle Scherrer-Crosbie and Cowart, {Lauren Ashley} and Parks, {John S.} and Lei Zhao and David Gordon and Francisco Ramirez-Valle and Margulies, {Kenneth B.} and Cappola, {Thomas P.} and Desai, {Ankit A.} and Pedersen, {Lauren N.} and Carmen Bergom and Nathan Stitziel and Michael Rettig and John Dipersio and Stefan Hajny and Christina Christoffersen and Abhinav Diwan and Ali Javaheri",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = mar,

doi = "10.1016/j.jacbts.2022.09.010",

language = "English",

volume = "8",

pages = "340--355",

journal = "JACC: Basic to Translational Science",

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Guo, Z, Valenzuela Ripoll, C, Picataggi, A, Rawnsley, D, Ozcan, M, Chirinos, JA, Chendamarai, E, Girardi, A, Riehl, T, Evie, H, Diab, A, Kovacs, A , Hyrc, K , Ma, X, Asnani, A, Shewale, SV, Scherrer-Crosbie, M, Cowart, LA, Parks, JS, Zhao, L, Gordon, D, Ramirez-Valle, F, Margulies, KB, Cappola, TP, Desai, AA, Pedersen, LN, Bergom, C , Stitziel, N , Rettig, M , Dipersio, J, Hajny, S, Christoffersen, C, Diwan, A & Javaheri, A 2023, 'Apolipoprotein M Attenuates Anthracycline Cardiotoxicity and Lysosomal Injury', JACC: Basic to Translational Science, vol. 8, no. 3, pp. 340-355. https://doi.org/10.1016/j.jacbts.2022.09.010

TY - JOUR

T1 - Apolipoprotein M Attenuates Anthracycline Cardiotoxicity and Lysosomal Injury

AU - Guo, Zhen

AU - Valenzuela Ripoll, Carla

AU - Picataggi, Antonino

AU - Rawnsley, David

AU - Ozcan, Mualla

AU - Chirinos, Julio A.

AU - Chendamarai, Ezhilarasi

AU - Girardi, Amanda

AU - Riehl, Terrence

AU - Evie, Hosannah

AU - Diab, Ahmed

AU - Kovacs, Attila

AU - Hyrc, Krzysztof

AU - Ma, Xiucui

AU - Asnani, Aarti

AU - Shewale, Swapnil V.

AU - Scherrer-Crosbie, Marielle

AU - Cowart, Lauren Ashley

AU - Parks, John S.

AU - Zhao, Lei

AU - Gordon, David

AU - Ramirez-Valle, Francisco

AU - Margulies, Kenneth B.

AU - Cappola, Thomas P.

AU - Desai, Ankit A.

AU - Pedersen, Lauren N.

AU - Bergom, Carmen

AU - Stitziel, Nathan

AU - Rettig, Michael

AU - Dipersio, John

AU - Hajny, Stefan

AU - Christoffersen, Christina

AU - Diwan, Abhinav

AU - Javaheri, Ali

PY - 2023/3

Y1 - 2023/3

N2 - Apolipoprotein M (ApoM) binds sphingosine-1-phosphate (S1P) and is inversely associated with mortality in human heart failure (HF). Here, we show that anthracyclines such as doxorubicin (Dox) reduce circulating ApoM in mice and humans, that ApoM is inversely associated with mortality in patients with anthracycline-induced heart failure, and ApoM heterozygosity in mice increases Dox-induced mortality. In the setting of Dox stress, our studies suggest ApoM can help sustain myocardial autophagic flux in a post-transcriptional manner, attenuate Dox cardiotoxicity, and prevent lysosomal injury.

AB - Apolipoprotein M (ApoM) binds sphingosine-1-phosphate (S1P) and is inversely associated with mortality in human heart failure (HF). Here, we show that anthracyclines such as doxorubicin (Dox) reduce circulating ApoM in mice and humans, that ApoM is inversely associated with mortality in patients with anthracycline-induced heart failure, and ApoM heterozygosity in mice increases Dox-induced mortality. In the setting of Dox stress, our studies suggest ApoM can help sustain myocardial autophagic flux in a post-transcriptional manner, attenuate Dox cardiotoxicity, and prevent lysosomal injury.

KW - TFEB

KW - anthracycline

KW - apolipoprotein M

KW - autophagy

KW - cardiomyopathy

UR - http://www.scopus.com/inward/record.url?scp=85150029297&partnerID=8YFLogxK

U2 - 10.1016/j.jacbts.2022.09.010

DO - 10.1016/j.jacbts.2022.09.010

M3 - Article

C2 - 37034289

AN - SCOPUS:85150029297

SN - 2452-302X

VL - 8

SP - 340

EP - 355

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 3

ER -

Apolipoprotein M Attenuates Anthracycline Cardiotoxicity and Lysosomal Injury

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