Glomerular filtrate proteins in acute cardiorenal syndrome

Rumie Wakasaki, Katsuyuki Matsushita, Kirsti Golgotiu, Sharon Anderson, Mahaba B. Eiwaz, Daniel J. Orton, Sang Jun Han, H. Thomas Lee, Richard D. Smith, Karin D. Rodland, Paul D. Piehowski, Michael Hutchens

Research output: Contribution to journalArticle

Abstract

Acute cardiorenal syndrome (CRS-1) is a morbid complication of acute cardiovascular disease. Heart-to-kidney signals transmitted by "cardiorenal connectors" have been postulated, but investigation into CRS-1 has been limited by technical limitations and a paucity of models. To address these limitations, we developed a translational model of CRS-1, cardiac arrest and cardiopulmonary resuscitation (CA/CPR), and now report findings from nanoscale mass spectrometry proteomic exploration of glomerular filtrate 2 hours after CA/CPR or sham procedure. Filtrate acquisition was confirmed by imaging, molecular weight and charge distribution, and exclusion of protein specific to surrounding cells. Filtration of proteins specific to the heart was detected following CA/CPR and confirmed with mass spectrometry performed using urine collections from mice with deficient tubular endocytosis. Cardiac LIM protein was a CA/CPR-specific filtrate component. Cardiac arrest induced plasma release of cardiac LIM protein in mice and critically ill human cardiac arrest survivors, and administration of recombinant cardiac LIM protein to mice altered renal function. These findings demonstrate that glomerular filtrate is accessible to nanoscale proteomics and elucidate the population of proteins filtered 2 hours after CA/CPR. The identification of cardiac-specific proteins in renal filtrate suggests a novel signaling mechanism in CRS-1. We expect these findings to advance understanding of CRS-1.

Original languageEnglish (US)
JournalJCI insight
Volume4
Issue number4
DOIs
StatePublished - Feb 21 2019

Fingerprint

Cardio-Renal Syndrome
Heart Arrest
Cardiopulmonary Resuscitation
Proteins
Kidney
Proteomics
Mass Spectrometry
Induced Heart Arrest
Urine Specimen Collection
Acute Disease
Endocytosis
Critical Illness
Cardiovascular Diseases
Molecular Weight

Keywords

  • Cardiology
  • Cardiovascular disease
  • Nephrology
  • Protein traffic
  • Proteomics

Cite this

Glomerular filtrate proteins in acute cardiorenal syndrome. / Wakasaki, Rumie; Matsushita, Katsuyuki; Golgotiu, Kirsti; Anderson, Sharon; Eiwaz, Mahaba B.; Orton, Daniel J.; Han, Sang Jun; Lee, H. Thomas; Smith, Richard D.; Rodland, Karin D.; Piehowski, Paul D.; Hutchens, Michael.

In: JCI insight, Vol. 4, No. 4, 21.02.2019.

Research output: Contribution to journalArticle

Wakasaki, R, Matsushita, K, Golgotiu, K, Anderson, S, Eiwaz, MB, Orton, DJ, Han, SJ, Lee, HT, Smith, RD, Rodland, KD, Piehowski, PD & Hutchens, M 2019, 'Glomerular filtrate proteins in acute cardiorenal syndrome', JCI insight, vol. 4, no. 4. https://doi.org/10.1172/jci.insight.122130
Wakasaki R, Matsushita K, Golgotiu K, Anderson S, Eiwaz MB, Orton DJ et al. Glomerular filtrate proteins in acute cardiorenal syndrome. JCI insight. 2019 Feb 21;4(4). https://doi.org/10.1172/jci.insight.122130
Wakasaki, Rumie ; Matsushita, Katsuyuki ; Golgotiu, Kirsti ; Anderson, Sharon ; Eiwaz, Mahaba B. ; Orton, Daniel J. ; Han, Sang Jun ; Lee, H. Thomas ; Smith, Richard D. ; Rodland, Karin D. ; Piehowski, Paul D. ; Hutchens, Michael. / Glomerular filtrate proteins in acute cardiorenal syndrome. In: JCI insight. 2019 ; Vol. 4, No. 4.
@article{69ab768d78ed4b6d85f5a847fb9cbde4,
title = "Glomerular filtrate proteins in acute cardiorenal syndrome",
abstract = "Acute cardiorenal syndrome (CRS-1) is a morbid complication of acute cardiovascular disease. Heart-to-kidney signals transmitted by {"}cardiorenal connectors{"} have been postulated, but investigation into CRS-1 has been limited by technical limitations and a paucity of models. To address these limitations, we developed a translational model of CRS-1, cardiac arrest and cardiopulmonary resuscitation (CA/CPR), and now report findings from nanoscale mass spectrometry proteomic exploration of glomerular filtrate 2 hours after CA/CPR or sham procedure. Filtrate acquisition was confirmed by imaging, molecular weight and charge distribution, and exclusion of protein specific to surrounding cells. Filtration of proteins specific to the heart was detected following CA/CPR and confirmed with mass spectrometry performed using urine collections from mice with deficient tubular endocytosis. Cardiac LIM protein was a CA/CPR-specific filtrate component. Cardiac arrest induced plasma release of cardiac LIM protein in mice and critically ill human cardiac arrest survivors, and administration of recombinant cardiac LIM protein to mice altered renal function. These findings demonstrate that glomerular filtrate is accessible to nanoscale proteomics and elucidate the population of proteins filtered 2 hours after CA/CPR. The identification of cardiac-specific proteins in renal filtrate suggests a novel signaling mechanism in CRS-1. We expect these findings to advance understanding of CRS-1.",
keywords = "Cardiology, Cardiovascular disease, Nephrology, Protein traffic, Proteomics",
author = "Rumie Wakasaki and Katsuyuki Matsushita and Kirsti Golgotiu and Sharon Anderson and Eiwaz, {Mahaba B.} and Orton, {Daniel J.} and Han, {Sang Jun} and Lee, {H. Thomas} and Smith, {Richard D.} and Rodland, {Karin D.} and Piehowski, {Paul D.} and Michael Hutchens",
year = "2019",
month = "2",
day = "21",
doi = "10.1172/jci.insight.122130",
language = "English (US)",
volume = "4",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "4",

}

TY - JOUR

T1 - Glomerular filtrate proteins in acute cardiorenal syndrome

AU - Wakasaki, Rumie

AU - Matsushita, Katsuyuki

AU - Golgotiu, Kirsti

AU - Anderson, Sharon

AU - Eiwaz, Mahaba B.

AU - Orton, Daniel J.

AU - Han, Sang Jun

AU - Lee, H. Thomas

AU - Smith, Richard D.

AU - Rodland, Karin D.

AU - Piehowski, Paul D.

AU - Hutchens, Michael

PY - 2019/2/21

Y1 - 2019/2/21

N2 - Acute cardiorenal syndrome (CRS-1) is a morbid complication of acute cardiovascular disease. Heart-to-kidney signals transmitted by "cardiorenal connectors" have been postulated, but investigation into CRS-1 has been limited by technical limitations and a paucity of models. To address these limitations, we developed a translational model of CRS-1, cardiac arrest and cardiopulmonary resuscitation (CA/CPR), and now report findings from nanoscale mass spectrometry proteomic exploration of glomerular filtrate 2 hours after CA/CPR or sham procedure. Filtrate acquisition was confirmed by imaging, molecular weight and charge distribution, and exclusion of protein specific to surrounding cells. Filtration of proteins specific to the heart was detected following CA/CPR and confirmed with mass spectrometry performed using urine collections from mice with deficient tubular endocytosis. Cardiac LIM protein was a CA/CPR-specific filtrate component. Cardiac arrest induced plasma release of cardiac LIM protein in mice and critically ill human cardiac arrest survivors, and administration of recombinant cardiac LIM protein to mice altered renal function. These findings demonstrate that glomerular filtrate is accessible to nanoscale proteomics and elucidate the population of proteins filtered 2 hours after CA/CPR. The identification of cardiac-specific proteins in renal filtrate suggests a novel signaling mechanism in CRS-1. We expect these findings to advance understanding of CRS-1.

AB - Acute cardiorenal syndrome (CRS-1) is a morbid complication of acute cardiovascular disease. Heart-to-kidney signals transmitted by "cardiorenal connectors" have been postulated, but investigation into CRS-1 has been limited by technical limitations and a paucity of models. To address these limitations, we developed a translational model of CRS-1, cardiac arrest and cardiopulmonary resuscitation (CA/CPR), and now report findings from nanoscale mass spectrometry proteomic exploration of glomerular filtrate 2 hours after CA/CPR or sham procedure. Filtrate acquisition was confirmed by imaging, molecular weight and charge distribution, and exclusion of protein specific to surrounding cells. Filtration of proteins specific to the heart was detected following CA/CPR and confirmed with mass spectrometry performed using urine collections from mice with deficient tubular endocytosis. Cardiac LIM protein was a CA/CPR-specific filtrate component. Cardiac arrest induced plasma release of cardiac LIM protein in mice and critically ill human cardiac arrest survivors, and administration of recombinant cardiac LIM protein to mice altered renal function. These findings demonstrate that glomerular filtrate is accessible to nanoscale proteomics and elucidate the population of proteins filtered 2 hours after CA/CPR. The identification of cardiac-specific proteins in renal filtrate suggests a novel signaling mechanism in CRS-1. We expect these findings to advance understanding of CRS-1.

KW - Cardiology

KW - Cardiovascular disease

KW - Nephrology

KW - Protein traffic

KW - Proteomics

UR - http://www.scopus.com/inward/record.url?scp=85062385181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062385181&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.122130

DO - 10.1172/jci.insight.122130

M3 - Article

VL - 4

JO - JCI insight

JF - JCI insight

SN - 2379-3708

IS - 4

ER -