Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Cardiac ATP production and contractility are favorably regulated by short-term S100A9 blockade after myocardial infarction

Boteanu, Raluca M. ; Suica, Viorel I. ; Uyy, Elena ; Ivan, Luminita ; Uta, Diana V. ; Mares, Razvan G. ; Simionescu, Maya ; Schiopu, Alexandru LU orcid and Antohe, Felicia (2025) In Journal of Advanced Research
Abstract

Introduction: The infarcted heart is energetically compromised exhibiting a deficient production of adenosine triphosphate (ATP) and the ensuing impaired contractile function. Short-term blockade of the protein S100A9 improves cardiac performance in mice after myocardial infarction (MI). The implications upon ATP production during this process are not known. Objectives: This study evaluates whether S100A9 blockade effects ATP synthesis and cardiac contractility in C57BL/6 mice at seven days post-MI. Methods: Three experimental groups were used: (i) mice with MI, induced by permanent left coronary ligation, (ii) mice with MI, short-term treated with the S100A9 blocker ABR-238901, and (iii) sham (control) mice. After removing the left... (More)

Introduction: The infarcted heart is energetically compromised exhibiting a deficient production of adenosine triphosphate (ATP) and the ensuing impaired contractile function. Short-term blockade of the protein S100A9 improves cardiac performance in mice after myocardial infarction (MI). The implications upon ATP production during this process are not known. Objectives: This study evaluates whether S100A9 blockade effects ATP synthesis and cardiac contractility in C57BL/6 mice at seven days post-MI. Methods: Three experimental groups were used: (i) mice with MI, induced by permanent left coronary ligation, (ii) mice with MI, short-term treated with the S100A9 blocker ABR-238901, and (iii) sham (control) mice. After removing the left ventricle, mass spectrometry, pathway enrichment analysis, Western blot, RT-PCR and pharmacological network analysis were performed. Results: A number of 600 differentially abundant proteins (DAPs) was significantly altered by the S100A9 blocker in MI-treated mice compared with MI mice. Some of these proteins were associated with oxidative phosphorylation, citrate cycle (TCA), mitochondrial fatty acid beta-oxidation, glycolysis and cardiac muscle contraction pathways. In the ischemic ventricle, ABR-238901 treatment increased (1.8- to 38-fold) the abundance of proteins NDUFAB1, UQCRC1, HADHA, ACAA2, ALDOA, PKM1, DLD, DLAT, PDHX, ACO2, IDH3A, FH1, CKM, CKMT2, TNNC1, crucial for early cellular metabolic changes, ATP distribution and contractility. The cardiac level of ATP increased (1.8-fold, p < 0.05) in MI mice treated with ABR-238901 compared to MI mice. The network pharmacology analysis uncovered potential pharmacologic targets of ABR-238901 that may interact with DAPs related to ATP production and contractility. Conclusion: Short-term S100A9 blockade effectively regulates the proteins implicated in ATP production and cardiac contractility post-MI, providing a framework for future cardiac energy metabolism studies.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
Cardiac contractility, Energy metabolic pathways, Myocardial infarction, Proteomic analysis, S100A9 blockade
in
Journal of Advanced Research
publisher
Elsevier
external identifiers
  • scopus:85217456291
  • pmid:39870300
ISSN
2090-1232
DOI
10.1016/j.jare.2025.01.041
language
English
LU publication?
yes
id
4b8e2e13-4483-4988-9bbe-611acf2a8678
date added to LUP
2025-04-09 09:52:54
date last changed
2025-07-16 17:42:28
@article{4b8e2e13-4483-4988-9bbe-611acf2a8678,
  abstract     = {{<p>Introduction: The infarcted heart is energetically compromised exhibiting a deficient production of adenosine triphosphate (ATP) and the ensuing impaired contractile function. Short-term blockade of the protein S100A9 improves cardiac performance in mice after myocardial infarction (MI). The implications upon ATP production during this process are not known. Objectives: This study evaluates whether S100A9 blockade effects ATP synthesis and cardiac contractility in C57BL/6 mice at seven days post-MI. Methods: Three experimental groups were used: (i) mice with MI, induced by permanent left coronary ligation, (ii) mice with MI, short-term treated with the S100A9 blocker ABR-238901, and (iii) sham (control) mice. After removing the left ventricle, mass spectrometry, pathway enrichment analysis, Western blot, RT-PCR and pharmacological network analysis were performed. Results: A number of 600 differentially abundant proteins (DAPs) was significantly altered by the S100A9 blocker in MI-treated mice compared with MI mice. Some of these proteins were associated with oxidative phosphorylation, citrate cycle (TCA), mitochondrial fatty acid beta-oxidation, glycolysis and cardiac muscle contraction pathways. In the ischemic ventricle, ABR-238901 treatment increased (1.8- to 38-fold) the abundance of proteins NDUFAB1, UQCRC1, HADHA, ACAA2, ALDOA, PKM1, DLD, DLAT, PDHX, ACO2, IDH3A, FH1, CKM, CKMT2, TNNC1, crucial for early cellular metabolic changes, ATP distribution and contractility. The cardiac level of ATP increased (1.8-fold, p &lt; 0.05) in MI mice treated with ABR-238901 compared to MI mice. The network pharmacology analysis uncovered potential pharmacologic targets of ABR-238901 that may interact with DAPs related to ATP production and contractility. Conclusion: Short-term S100A9 blockade effectively regulates the proteins implicated in ATP production and cardiac contractility post-MI, providing a framework for future cardiac energy metabolism studies.</p>}},
  author       = {{Boteanu, Raluca M. and Suica, Viorel I. and Uyy, Elena and Ivan, Luminita and Uta, Diana V. and Mares, Razvan G. and Simionescu, Maya and Schiopu, Alexandru and Antohe, Felicia}},
  issn         = {{2090-1232}},
  keywords     = {{Cardiac contractility; Energy metabolic pathways; Myocardial infarction; Proteomic analysis; S100A9 blockade}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Advanced Research}},
  title        = {{Cardiac ATP production and contractility are favorably regulated by short-term S100A9 blockade after myocardial infarction}},
  url          = {{http://dx.doi.org/10.1016/j.jare.2025.01.041}},
  doi          = {{10.1016/j.jare.2025.01.041}},
  year         = {{2025}},
}