Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways

IPAC; IMAC2 Investigators; Jana P. Lovell; Kevin Bermea; Jinsheng Yu; Sylvie Rousseau; Charles D. Cohen; Aashik Bhalodia; Marcelle Dina Zita; Richard D. Head; Roger S. Blumenthal; Rami Alharethi; Julie Damp; John Boehmer; Jeffrey Alexis; Dennis M. McNamara; Garima Sharma; Luigi Adamo; Dennis M. aaaMcNamara; James D. Fett; Jessica Pisarcik; Charles McTiernan; Karen Hanley-Yanez; John Gorcsan; Erik Schelbert; Kismet Rasmusson; Kim Brunisholz; Amy Butler; Deborah Budge; A. G. Kfoury; Benjamin Horne; Joe Tuinei; Heather Brown; Allen J. Naftilan; Jill Russell; Darla Freehardt; Eileen Hsich; Cynthia Oblak; Greg Ewald; Donna Whitehead; Jean Flanagan; Anne Platts; Uri Elkayam; Jorge Caro; Stephanie Mullin; Michael M. Givertz; M. Susan Anello; Navin Rajagopalan; David Booth; Tiffany Sandlin; Wendy Wijesiri; Leslie T. Cooper; Lori A. Blauwet; Joann Brunner; Mary Phelps; Ruth Kempf; Kalgi Modi; Tracy Norwood; Joan Briller; Decebal Sorin Griza; G. Michael Felker; Robb Kociol; Patricia Adams; Gretchen Wells; Vinay Thohan; Deborah Wesley-Farrington; Sandra Soots; Richard Sheppard; Caroline Michel; Nathalie Lapointe; Heather Nathaniel; Angela Kealey; Marc Semigran; Maureen Daher; David Silber; Eric Popjes; Patricia Frey; Todd Nicklas; Lori Caufield; John W. Thornton; Mindy Gentry; Vincent J.B. Robinson; Gyanendra K. Sharma; Joan Holloway; Maria Powell; David Markham; Mark Drazner; Lynn Fernandez; Mark Zucker; David A. Baran; Martin L. Gimovsky; Natalia Hochbaum; Bharati Patel; Laura Adams; Gautam Ramani; Stephen Gottlieb; Shawn Robinson; Stacy Fisher; Joanne Marshall; Jennifer Haythe; Donna Mancini; Rachel Bijou; Maryjane Farr; Marybeth Marks; Henry Arango; Biykem Bozkurt; Mariana Bolos; Paul Mather; Sharon Rubin; Raphael Bonita; Susan Eberwine; Hal Skopicki; Kathleen Stergiopoulos; Ellen McCathy-Santoro; Jennifer Intravaia; Elizabeth Maas; Jordan Safirstein; Audrey Kleet; Nancy Martinez; Christine Corpoin; Donna Hesari; Sandra Chaparro; Laura J. Hudson; Jalal K. Ghali; Zora Injic; Ilan S. Wittstein; Karen Janosko; Barry London; Hidekazu Tanaka; Mathew Suffoletto; Randall C. Starling; Annette McNallan; Lu Anne Koenig; Natalie Pierson; Yanique Bell; Alicia Ervin; Janice Schrack; Pam LaDuke; Guillermo Torre-Amione; Jeannie Arredondo; Daniel F. Pauly; Pamela C. Smith; Stephanie Fuoco; Elayne Breton; Deborah Wesley; G. William Dec; Diane Cocca-Spofford; David W. Markham; Colleen Debes; Mark J. Zucker; Peter Liu; Judith Renton; Jagat Narula; Byron Allen; Elizabeth Westberg

doi:10.1016/j.jchf.2023.05.031

Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways

IPAC, IMAC2 Investigators, Jana P. Lovell, Kevin Bermea, Jinsheng Yu, Sylvie Rousseau, Charles D. Cohen, Aashik Bhalodia, Marcelle Dina Zita, Richard D. Head, Roger S. Blumenthal, Rami Alharethi, Julie Damp, John Boehmer, Jeffrey Alexis, Dennis M. McNamara, Garima Sharma, Luigi Adamo, Dennis M. aaaMcNamara, James D. FettJessica Pisarcik, Charles McTiernan, Karen Hanley-Yanez, John Gorcsan, Erik Schelbert, Kismet Rasmusson, Kim Brunisholz, Amy Butler, Deborah Budge, A. G. Kfoury, Benjamin Horne, Joe Tuinei, Heather Brown, Allen J. Naftilan, Jill Russell, Darla Freehardt, Eileen Hsich, Cynthia Oblak, Greg Ewald, Donna Whitehead, Jean Flanagan, Anne Platts, Uri Elkayam, Jorge Caro, Stephanie Mullin, Michael M. Givertz, M. Susan Anello, Navin Rajagopalan, David Booth, Tiffany Sandlin, Wendy Wijesiri, Leslie T. Cooper, Lori A. Blauwet, Joann Brunner, Mary Phelps, Ruth Kempf, Kalgi Modi, Tracy Norwood, Joan Briller, Decebal Sorin Griza, G. Michael Felker, Robb Kociol, Patricia Adams, Gretchen Wells, Vinay Thohan, Deborah Wesley-Farrington, Sandra Soots, Richard Sheppard, Caroline Michel, Nathalie Lapointe, Heather Nathaniel, Angela Kealey, Marc Semigran, Maureen Daher, David Silber, Eric Popjes, Patricia Frey, Todd Nicklas, Lori Caufield, John W. Thornton, Mindy Gentry, Vincent J.B. Robinson, Gyanendra K. Sharma, Joan Holloway, Maria Powell, David Markham, Mark Drazner, Lynn Fernandez, Mark Zucker, David A. Baran, Martin L. Gimovsky, Natalia Hochbaum, Bharati Patel, Laura Adams, Gautam Ramani, Stephen Gottlieb, Shawn Robinson, Stacy Fisher, Joanne Marshall, Jennifer Haythe, Donna Mancini, Rachel Bijou, Maryjane Farr, Marybeth Marks, Henry Arango, Biykem Bozkurt, Mariana Bolos, Paul Mather, Sharon Rubin, Raphael Bonita, Susan Eberwine, Hal Skopicki, Kathleen Stergiopoulos, Ellen McCathy-Santoro, Jennifer Intravaia, Elizabeth Maas, Jordan Safirstein, Audrey Kleet, Nancy Martinez, Christine Corpoin, Donna Hesari, Sandra Chaparro, Laura J. Hudson, Jalal K. Ghali, Zora Injic, Ilan S. Wittstein, Karen Janosko, Barry London, Hidekazu Tanaka, Mathew Suffoletto, Randall C. Starling, Annette McNallan, Lu Anne Koenig, Natalie Pierson, Yanique Bell, Alicia Ervin, Janice Schrack, Pam LaDuke, Guillermo Torre-Amione, Jeannie Arredondo, Daniel F. Pauly, Pamela C. Smith, Stephanie Fuoco, Elayne Breton, Deborah Wesley, G. William Dec, Diane Cocca-Spofford, David W. Markham, Colleen Debes, Mark J. Zucker, Peter Liu, Judith Renton, Jagat Narula, Byron Allen, Elizabeth Westberg

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

8 Scopus citations

Abstract

Background: The pathophysiology of peripartum cardiomyopathy (PPCM) and its distinctive biological features remain incompletely understood. High-throughput serum proteomic profiling, a powerful tool to gain insights into the pathophysiology of diseases at a systems biology level, has never been used to investigate PPCM relative to nonischemic cardiomyopathy. Objectives: The aim of this study was to characterize the pathophysiology of PPCM through serum proteomic analysis. Methods: Aptamer-based proteomic analysis (SomaScan 7K) was performed on serum samples from women with PPCM (n = 67), women with nonischemic nonperipartum cardiomyopathy (NPCM) (n = 31), and age-matched healthy peripartum and nonperipartum women (n = 10 each). Serum samples were obtained from the IPAC (Investigation of Pregnancy-Associated Cardiomyopathy) and IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) studies. Results: Principal component analysis revealed unique clustering of each patient group (P for difference <0.001). Biological pathway analyses of differentially measured proteins in PPCM relative to NPCM, before and after normalization to pertinent healthy controls, highlighted specific dysregulation of inflammatory pathways in PPCM, including the upregulation of the cholesterol metabolism-related anti-inflammatory pathway liver-X receptor/retinoid-X receptor (LXR/RXR) (P < 0.01, Z-score 1.9-2.1). Cardiac recovery by 12 months in PPCM was associated with the downregulation of pro-inflammatory pathways and the upregulation of LXR/RXR, and an additional RXR-dependent pathway involved in the regulation of inflammation and metabolism, peroxisome proliferator-activated receptor α/RXRα signaling. Conclusions: Serum proteomic profiling of PPCM relative to NPCM and healthy controls indicated that PPCM is a distinct disease entity characterized by the unique dysregulation of inflammation-related pathways and cholesterol metabolism-related anti-inflammatory pathways. These findings provide insight into the pathophysiology of PPCM and point to novel potential therapeutic targets.

Original language	English
Pages (from-to)	1231-1242
Number of pages	12
Journal	JACC: Heart Failure
Volume	11
Issue number	9
DOIs	https://doi.org/10.1016/j.jchf.2023.05.031
State	Published - Sep 2023

Keywords

heart failure
inflammation
pregnancy
proteomics
serum proteomics

Access to Document

10.1016/j.jchf.2023.05.031

Cite this

IPAC, IMAC2 Investigators, Lovell, J. P., Bermea, K., Yu, J., Rousseau, S., Cohen, C. D., Bhalodia, A., Zita, M. D., Head, R. D., Blumenthal, R. S., Alharethi, R., Damp, J., Boehmer, J., Alexis, J., McNamara, D. M., Sharma, G., Adamo, L., aaaMcNamara, D. M., ... Westberg, E. (2023). Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways. JACC: Heart Failure, 11(9), 1231-1242. https://doi.org/10.1016/j.jchf.2023.05.031

@article{1da666dc1dfc46409efbdd05737c9120,

title = "Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways",

abstract = "Background: The pathophysiology of peripartum cardiomyopathy (PPCM) and its distinctive biological features remain incompletely understood. High-throughput serum proteomic profiling, a powerful tool to gain insights into the pathophysiology of diseases at a systems biology level, has never been used to investigate PPCM relative to nonischemic cardiomyopathy. Objectives: The aim of this study was to characterize the pathophysiology of PPCM through serum proteomic analysis. Methods: Aptamer-based proteomic analysis (SomaScan 7K) was performed on serum samples from women with PPCM (n = 67), women with nonischemic nonperipartum cardiomyopathy (NPCM) (n = 31), and age-matched healthy peripartum and nonperipartum women (n = 10 each). Serum samples were obtained from the IPAC (Investigation of Pregnancy-Associated Cardiomyopathy) and IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) studies. Results: Principal component analysis revealed unique clustering of each patient group (P for difference <0.001). Biological pathway analyses of differentially measured proteins in PPCM relative to NPCM, before and after normalization to pertinent healthy controls, highlighted specific dysregulation of inflammatory pathways in PPCM, including the upregulation of the cholesterol metabolism-related anti-inflammatory pathway liver-X receptor/retinoid-X receptor (LXR/RXR) (P < 0.01, Z-score 1.9-2.1). Cardiac recovery by 12 months in PPCM was associated with the downregulation of pro-inflammatory pathways and the upregulation of LXR/RXR, and an additional RXR-dependent pathway involved in the regulation of inflammation and metabolism, peroxisome proliferator-activated receptor α/RXRα signaling. Conclusions: Serum proteomic profiling of PPCM relative to NPCM and healthy controls indicated that PPCM is a distinct disease entity characterized by the unique dysregulation of inflammation-related pathways and cholesterol metabolism-related anti-inflammatory pathways. These findings provide insight into the pathophysiology of PPCM and point to novel potential therapeutic targets.",

keywords = "heart failure, inflammation, pregnancy, proteomics, serum proteomics",

author = "IPAC and {IMAC2 Investigators} and Lovell, {Jana P.} and Kevin Bermea and Jinsheng Yu and Sylvie Rousseau and Cohen, {Charles D.} and Aashik Bhalodia and Zita, {Marcelle Dina} and Head, {Richard D.} and Blumenthal, {Roger S.} and Rami Alharethi and Julie Damp and John Boehmer and Jeffrey Alexis and McNamara, {Dennis M.} and Garima Sharma and Luigi Adamo and aaaMcNamara, {Dennis M.} and Fett, {James D.} and Jessica Pisarcik and Charles McTiernan and Karen Hanley-Yanez and John Gorcsan and Erik Schelbert and Kismet Rasmusson and Kim Brunisholz and Amy Butler and Deborah Budge and Kfoury, {A. G.} and Benjamin Horne and Joe Tuinei and Heather Brown and Naftilan, {Allen J.} and Jill Russell and Darla Freehardt and Eileen Hsich and Cynthia Oblak and Greg Ewald and Donna Whitehead and Jean Flanagan and Anne Platts and Uri Elkayam and Jorge Caro and Stephanie Mullin and Givertz, {Michael M.} and Anello, {M. Susan} and Navin Rajagopalan and David Booth and Tiffany Sandlin and Wendy Wijesiri and Cooper, {Leslie T.} and Blauwet, {Lori A.} and Joann Brunner and Mary Phelps and Ruth Kempf and Kalgi Modi and Tracy Norwood and Joan Briller and Griza, {Decebal Sorin} and Felker, {G. Michael} and Robb Kociol and Patricia Adams and Gretchen Wells and Vinay Thohan and Deborah Wesley-Farrington and Sandra Soots and Richard Sheppard and Caroline Michel and Nathalie Lapointe and Heather Nathaniel and Angela Kealey and Marc Semigran and Maureen Daher and David Silber and Eric Popjes and Patricia Frey and Todd Nicklas and Lori Caufield and Thornton, {John W.} and Mindy Gentry and Robinson, {Vincent J.B.} and Sharma, {Gyanendra K.} and Joan Holloway and Maria Powell and David Markham and Mark Drazner and Lynn Fernandez and Mark Zucker and Baran, {David A.} and Gimovsky, {Martin L.} and Natalia Hochbaum and Bharati Patel and Laura Adams and Gautam Ramani and Stephen Gottlieb and Shawn Robinson and Stacy Fisher and Joanne Marshall and Jennifer Haythe and Donna Mancini and Rachel Bijou and Maryjane Farr and Marybeth Marks and Henry Arango and Biykem Bozkurt and Mariana Bolos and Paul Mather and Sharon Rubin and Raphael Bonita and Susan Eberwine and Hal Skopicki and Kathleen Stergiopoulos and Ellen McCathy-Santoro and Jennifer Intravaia and Elizabeth Maas and Jordan Safirstein and Audrey Kleet and Nancy Martinez and Christine Corpoin and Donna Hesari and Sandra Chaparro and Hudson, {Laura J.} and Ghali, {Jalal K.} and Zora Injic and Wittstein, {Ilan S.} and Karen Janosko and Barry London and Hidekazu Tanaka and Mathew Suffoletto and Starling, {Randall C.} and Annette McNallan and Koenig, {Lu Anne} and Natalie Pierson and Yanique Bell and Alicia Ervin and Janice Schrack and Pam LaDuke and Guillermo Torre-Amione and Jeannie Arredondo and Pauly, {Daniel F.} and Smith, {Pamela C.} and Stephanie Fuoco and Elayne Breton and Deborah Wesley and Dec, {G. William} and Diane Cocca-Spofford and Markham, {David W.} and Colleen Debes and Zucker, {Mark J.} and Peter Liu and Judith Renton and Jagat Narula and Byron Allen and Elizabeth Westberg",

note = "Publisher Copyright: {\textcopyright} 2023 American College of Cardiology Foundation",

year = "2023",

month = sep,

doi = "10.1016/j.jchf.2023.05.031",

language = "English",

volume = "11",

pages = "1231--1242",

journal = "JACC: Heart Failure",

issn = "2213-1779",

number = "9",

}

IPAC, IMAC2 Investigators, Lovell, JP, Bermea, K, Yu, J, Rousseau, S, Cohen, CD, Bhalodia, A, Zita, MD, Head, RD, Blumenthal, RS, Alharethi, R, Damp, J, Boehmer, J, Alexis, J, McNamara, DM, Sharma, G, Adamo, L, aaaMcNamara, DM, Fett, JD, Pisarcik, J, McTiernan, C, Hanley-Yanez, K, Gorcsan, J, Schelbert, E, Rasmusson, K, Brunisholz, K, Butler, A, Budge, D, Kfoury, AG, Horne, B, Tuinei, J, Brown, H, Naftilan, AJ, Russell, J, Freehardt, D, Hsich, E, Oblak, C, Ewald, G, Whitehead, D, Flanagan, J, Platts, A, Elkayam, U, Caro, J, Mullin, S, Givertz, MM, Anello, MS, Rajagopalan, N, Booth, D, Sandlin, T, Wijesiri, W, Cooper, LT, Blauwet, LA, Brunner, J, Phelps, M, Kempf, R, Modi, K, Norwood, T, Briller, J, Griza, DS, Felker, GM, Kociol, R, Adams, P, Wells, G, Thohan, V, Wesley-Farrington, D, Soots, S, Sheppard, R, Michel, C, Lapointe, N, Nathaniel, H, Kealey, A, Semigran, M, Daher, M, Silber, D, Popjes, E, Frey, P, Nicklas, T, Caufield, L, Thornton, JW, Gentry, M, Robinson, VJB, Sharma, GK, Holloway, J, Powell, M, Markham, D, Drazner, M, Fernandez, L, Zucker, M, Baran, DA, Gimovsky, ML, Hochbaum, N, Patel, B, Adams, L, Ramani, G, Gottlieb, S, Robinson, S, Fisher, S, Marshall, J, Haythe, J, Mancini, D, Bijou, R, Farr, M, Marks, M, Arango, H, Bozkurt, B, Bolos, M, Mather, P, Rubin, S, Bonita, R, Eberwine, S, Skopicki, H, Stergiopoulos, K, McCathy-Santoro, E, Intravaia, J, Maas, E, Safirstein, J, Kleet, A, Martinez, N, Corpoin, C, Hesari, D, Chaparro, S, Hudson, LJ, Ghali, JK, Injic, Z, Wittstein, IS, Janosko, K, London, B, Tanaka, H, Suffoletto, M, Starling, RC, McNallan, A, Koenig, LA, Pierson, N, Bell, Y, Ervin, A, Schrack, J, LaDuke, P, Torre-Amione, G, Arredondo, J, Pauly, DF, Smith, PC, Fuoco, S, Breton, E, Wesley, D, Dec, GW, Cocca-Spofford, D, Markham, DW, Debes, C, Zucker, MJ, Liu, P, Renton, J, Narula, J, Allen, B & Westberg, E 2023, 'Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways', JACC: Heart Failure, vol. 11, no. 9, pp. 1231-1242. https://doi.org/10.1016/j.jchf.2023.05.031

TY - JOUR

T1 - Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways

AU - IPAC

AU - IMAC2 Investigators

AU - Lovell, Jana P.

AU - Bermea, Kevin

AU - Yu, Jinsheng

AU - Rousseau, Sylvie

AU - Cohen, Charles D.

AU - Bhalodia, Aashik

AU - Zita, Marcelle Dina

AU - Head, Richard D.

AU - Blumenthal, Roger S.

AU - Alharethi, Rami

AU - Damp, Julie

AU - Boehmer, John

AU - Alexis, Jeffrey

AU - McNamara, Dennis M.

AU - Sharma, Garima

AU - Adamo, Luigi

AU - aaaMcNamara, Dennis M.

AU - Fett, James D.

AU - Pisarcik, Jessica

AU - McTiernan, Charles

AU - Hanley-Yanez, Karen

AU - Gorcsan, John

AU - Schelbert, Erik

AU - Rasmusson, Kismet

AU - Brunisholz, Kim

AU - Butler, Amy

AU - Budge, Deborah

AU - Kfoury, A. G.

AU - Horne, Benjamin

AU - Tuinei, Joe

AU - Brown, Heather

AU - Naftilan, Allen J.

AU - Russell, Jill

AU - Freehardt, Darla

AU - Hsich, Eileen

AU - Oblak, Cynthia

AU - Ewald, Greg

AU - Whitehead, Donna

AU - Flanagan, Jean

AU - Platts, Anne

AU - Elkayam, Uri

AU - Caro, Jorge

AU - Mullin, Stephanie

AU - Givertz, Michael M.

AU - Anello, M. Susan

AU - Rajagopalan, Navin

AU - Booth, David

AU - Sandlin, Tiffany

AU - Wijesiri, Wendy

AU - Cooper, Leslie T.

AU - Blauwet, Lori A.

AU - Brunner, Joann

AU - Phelps, Mary

AU - Kempf, Ruth

AU - Modi, Kalgi

AU - Norwood, Tracy

AU - Briller, Joan

AU - Griza, Decebal Sorin

AU - Felker, G. Michael

AU - Kociol, Robb

AU - Adams, Patricia

AU - Wells, Gretchen

AU - Thohan, Vinay

AU - Wesley-Farrington, Deborah

AU - Soots, Sandra

AU - Sheppard, Richard

AU - Michel, Caroline

AU - Lapointe, Nathalie

AU - Nathaniel, Heather

AU - Kealey, Angela

AU - Semigran, Marc

AU - Daher, Maureen

AU - Silber, David

AU - Popjes, Eric

AU - Frey, Patricia

AU - Nicklas, Todd

AU - Caufield, Lori

AU - Thornton, John W.

AU - Gentry, Mindy

AU - Robinson, Vincent J.B.

AU - Sharma, Gyanendra K.

AU - Holloway, Joan

AU - Powell, Maria

AU - Markham, David

AU - Drazner, Mark

AU - Fernandez, Lynn

AU - Zucker, Mark

AU - Baran, David A.

AU - Gimovsky, Martin L.

AU - Hochbaum, Natalia

AU - Patel, Bharati

AU - Adams, Laura

AU - Ramani, Gautam

AU - Gottlieb, Stephen

AU - Robinson, Shawn

AU - Fisher, Stacy

AU - Marshall, Joanne

AU - Haythe, Jennifer

AU - Mancini, Donna

AU - Bijou, Rachel

AU - Farr, Maryjane

AU - Marks, Marybeth

AU - Arango, Henry

AU - Bozkurt, Biykem

AU - Bolos, Mariana

AU - Mather, Paul

AU - Rubin, Sharon

AU - Bonita, Raphael

AU - Eberwine, Susan

AU - Skopicki, Hal

AU - Stergiopoulos, Kathleen

AU - McCathy-Santoro, Ellen

AU - Intravaia, Jennifer

AU - Maas, Elizabeth

AU - Safirstein, Jordan

AU - Kleet, Audrey

AU - Martinez, Nancy

AU - Corpoin, Christine

AU - Hesari, Donna

AU - Chaparro, Sandra

AU - Hudson, Laura J.

AU - Ghali, Jalal K.

AU - Injic, Zora

AU - Wittstein, Ilan S.

AU - Janosko, Karen

AU - London, Barry

AU - Tanaka, Hidekazu

AU - Suffoletto, Mathew

AU - Starling, Randall C.

AU - McNallan, Annette

AU - Koenig, Lu Anne

AU - Pierson, Natalie

AU - Bell, Yanique

AU - Ervin, Alicia

AU - Schrack, Janice

AU - LaDuke, Pam

AU - Torre-Amione, Guillermo

AU - Arredondo, Jeannie

AU - Pauly, Daniel F.

AU - Smith, Pamela C.

AU - Fuoco, Stephanie

AU - Breton, Elayne

AU - Wesley, Deborah

AU - Dec, G. William

AU - Cocca-Spofford, Diane

AU - Markham, David W.

AU - Debes, Colleen

AU - Zucker, Mark J.

AU - Liu, Peter

AU - Renton, Judith

AU - Narula, Jagat

AU - Allen, Byron

AU - Westberg, Elizabeth

PY - 2023/9

Y1 - 2023/9

N2 - Background: The pathophysiology of peripartum cardiomyopathy (PPCM) and its distinctive biological features remain incompletely understood. High-throughput serum proteomic profiling, a powerful tool to gain insights into the pathophysiology of diseases at a systems biology level, has never been used to investigate PPCM relative to nonischemic cardiomyopathy. Objectives: The aim of this study was to characterize the pathophysiology of PPCM through serum proteomic analysis. Methods: Aptamer-based proteomic analysis (SomaScan 7K) was performed on serum samples from women with PPCM (n = 67), women with nonischemic nonperipartum cardiomyopathy (NPCM) (n = 31), and age-matched healthy peripartum and nonperipartum women (n = 10 each). Serum samples were obtained from the IPAC (Investigation of Pregnancy-Associated Cardiomyopathy) and IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) studies. Results: Principal component analysis revealed unique clustering of each patient group (P for difference <0.001). Biological pathway analyses of differentially measured proteins in PPCM relative to NPCM, before and after normalization to pertinent healthy controls, highlighted specific dysregulation of inflammatory pathways in PPCM, including the upregulation of the cholesterol metabolism-related anti-inflammatory pathway liver-X receptor/retinoid-X receptor (LXR/RXR) (P < 0.01, Z-score 1.9-2.1). Cardiac recovery by 12 months in PPCM was associated with the downregulation of pro-inflammatory pathways and the upregulation of LXR/RXR, and an additional RXR-dependent pathway involved in the regulation of inflammation and metabolism, peroxisome proliferator-activated receptor α/RXRα signaling. Conclusions: Serum proteomic profiling of PPCM relative to NPCM and healthy controls indicated that PPCM is a distinct disease entity characterized by the unique dysregulation of inflammation-related pathways and cholesterol metabolism-related anti-inflammatory pathways. These findings provide insight into the pathophysiology of PPCM and point to novel potential therapeutic targets.

AB - Background: The pathophysiology of peripartum cardiomyopathy (PPCM) and its distinctive biological features remain incompletely understood. High-throughput serum proteomic profiling, a powerful tool to gain insights into the pathophysiology of diseases at a systems biology level, has never been used to investigate PPCM relative to nonischemic cardiomyopathy. Objectives: The aim of this study was to characterize the pathophysiology of PPCM through serum proteomic analysis. Methods: Aptamer-based proteomic analysis (SomaScan 7K) was performed on serum samples from women with PPCM (n = 67), women with nonischemic nonperipartum cardiomyopathy (NPCM) (n = 31), and age-matched healthy peripartum and nonperipartum women (n = 10 each). Serum samples were obtained from the IPAC (Investigation of Pregnancy-Associated Cardiomyopathy) and IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) studies. Results: Principal component analysis revealed unique clustering of each patient group (P for difference <0.001). Biological pathway analyses of differentially measured proteins in PPCM relative to NPCM, before and after normalization to pertinent healthy controls, highlighted specific dysregulation of inflammatory pathways in PPCM, including the upregulation of the cholesterol metabolism-related anti-inflammatory pathway liver-X receptor/retinoid-X receptor (LXR/RXR) (P < 0.01, Z-score 1.9-2.1). Cardiac recovery by 12 months in PPCM was associated with the downregulation of pro-inflammatory pathways and the upregulation of LXR/RXR, and an additional RXR-dependent pathway involved in the regulation of inflammation and metabolism, peroxisome proliferator-activated receptor α/RXRα signaling. Conclusions: Serum proteomic profiling of PPCM relative to NPCM and healthy controls indicated that PPCM is a distinct disease entity characterized by the unique dysregulation of inflammation-related pathways and cholesterol metabolism-related anti-inflammatory pathways. These findings provide insight into the pathophysiology of PPCM and point to novel potential therapeutic targets.

KW - heart failure

KW - inflammation

KW - pregnancy

KW - proteomics

KW - serum proteomics

UR - http://www.scopus.com/inward/record.url?scp=85168745004&partnerID=8YFLogxK

U2 - 10.1016/j.jchf.2023.05.031

DO - 10.1016/j.jchf.2023.05.031

M3 - Article

C2 - 37542511

AN - SCOPUS:85168745004

SN - 2213-1779

VL - 11

SP - 1231

EP - 1242

JO - JACC: Heart Failure

JF - JACC: Heart Failure

IS - 9

ER -

Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this