Cardiomyopathy, oxidative stress and impaired contractility in a rheumatoid arthritis mouse model

Gianluigi Pironti, Alex Bersellini-Farinotti, Nilesh M. Agalave, K. Sándor, Teresa Fernandez-Zafra, Alexandra Jurczak, Lars H. Lund, Camilla I. Svensson, Daniel C. Andersson

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objectives: Patients with rheumatoid arthritis (RA) display an increased risk of heart failure independent of traditional cardiovascular risk factors. To elucidate myocardial disease in RA, we have investigated molecular and cellular remodelling of the heart in an established mouse model of RA. Methods: The collagen antibody-induced arthritis (CAIA) RA mouse model is characterised by joint inflammation and increased inflammatory markers in the serum. We used CAIA mice in the postinflammatory phase that resembles medically controlled RA or RA in remission. Hearts were collected for cardiomyocyte isolation, biochemistry and histology analysis. Results: Hearts from mice subjected to CAIA displayed hypertrophy (heart/body weight, mean±SD: 5.9±0.8vs 5.1±0.7 mg/g, p<0.05), fibrosis and reduced left ventricular fractional shortening compared with control. Cardiomyocytes from CAIA mice showed reduced cytosolic [Ca2+]i transient amplitudes (F/F0, mean±SD: 3.0±1.2vs 3.6±1.5, p<0.05) that was linked to reductions in sarcoplasmic reticulum (SR) Ca2+ store (F/F0, mean±SD: 3.5±1.3vs 4.4±1.3, p<0.01) measured with Ca2+ imaging. This was associated to lower fractional shortening in the cardiomyocytes from the CAIA mice (%FS, mean±SD: 3.4±2.2 vs 4.6%±2.3%, p<0.05). Ca2+ handling proteins displayed oxidation-dependent posttranslational modifications that together with an increase in superoxide dismutase expression indicate a cell environment with oxidative stress. Conclusions: This study shows that inflammation during active RA has long-term consequences on molecular remodelling and contractile function of the heart, which further supports that rheumatology patients should be followed for development of heart failure.

Original languageEnglish
JournalHeart
DOIs
Publication statusAccepted/In press - May 26 2018

Fingerprint

Cardiomyopathies
Experimental Arthritis
Rheumatoid Arthritis
Oxidative Stress
Cardiac Myocytes
Antibodies
Heart Failure
Inflammation
Cardiomegaly
Rheumatology
Sarcoplasmic Reticulum
Post Translational Protein Processing
Biochemistry
Superoxide Dismutase
Histology
Fibrosis
Joints
Biomarkers
Body Weight
Proteins

Keywords

  • cardiac risk factors and prevention
  • heart disease
  • heart failure
  • myocardial disease basic science
  • translational cardiovascular science

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Pironti, G., Bersellini-Farinotti, A., Agalave, N. M., Sándor, K., Fernandez-Zafra, T., Jurczak, A., ... Andersson, D. C. (Accepted/In press). Cardiomyopathy, oxidative stress and impaired contractility in a rheumatoid arthritis mouse model. Heart. https://doi.org/10.1136/heartjnl-2018-312979

Cardiomyopathy, oxidative stress and impaired contractility in a rheumatoid arthritis mouse model. / Pironti, Gianluigi; Bersellini-Farinotti, Alex; Agalave, Nilesh M.; Sándor, K.; Fernandez-Zafra, Teresa; Jurczak, Alexandra; Lund, Lars H.; Svensson, Camilla I.; Andersson, Daniel C.

In: Heart, 26.05.2018.

Research output: Contribution to journalArticle

Pironti, G, Bersellini-Farinotti, A, Agalave, NM, Sándor, K, Fernandez-Zafra, T, Jurczak, A, Lund, LH, Svensson, CI & Andersson, DC 2018, 'Cardiomyopathy, oxidative stress and impaired contractility in a rheumatoid arthritis mouse model', Heart. https://doi.org/10.1136/heartjnl-2018-312979
Pironti, Gianluigi ; Bersellini-Farinotti, Alex ; Agalave, Nilesh M. ; Sándor, K. ; Fernandez-Zafra, Teresa ; Jurczak, Alexandra ; Lund, Lars H. ; Svensson, Camilla I. ; Andersson, Daniel C. / Cardiomyopathy, oxidative stress and impaired contractility in a rheumatoid arthritis mouse model. In: Heart. 2018.
@article{cc965ceade954fe7a0765d1e4a9f9b5e,
title = "Cardiomyopathy, oxidative stress and impaired contractility in a rheumatoid arthritis mouse model",
abstract = "Objectives: Patients with rheumatoid arthritis (RA) display an increased risk of heart failure independent of traditional cardiovascular risk factors. To elucidate myocardial disease in RA, we have investigated molecular and cellular remodelling of the heart in an established mouse model of RA. Methods: The collagen antibody-induced arthritis (CAIA) RA mouse model is characterised by joint inflammation and increased inflammatory markers in the serum. We used CAIA mice in the postinflammatory phase that resembles medically controlled RA or RA in remission. Hearts were collected for cardiomyocyte isolation, biochemistry and histology analysis. Results: Hearts from mice subjected to CAIA displayed hypertrophy (heart/body weight, mean±SD: 5.9±0.8vs 5.1±0.7 mg/g, p<0.05), fibrosis and reduced left ventricular fractional shortening compared with control. Cardiomyocytes from CAIA mice showed reduced cytosolic [Ca2+]i transient amplitudes (F/F0, mean±SD: 3.0±1.2vs 3.6±1.5, p<0.05) that was linked to reductions in sarcoplasmic reticulum (SR) Ca2+ store (F/F0, mean±SD: 3.5±1.3vs 4.4±1.3, p<0.01) measured with Ca2+ imaging. This was associated to lower fractional shortening in the cardiomyocytes from the CAIA mice ({\%}FS, mean±SD: 3.4±2.2 vs 4.6{\%}±2.3{\%}, p<0.05). Ca2+ handling proteins displayed oxidation-dependent posttranslational modifications that together with an increase in superoxide dismutase expression indicate a cell environment with oxidative stress. Conclusions: This study shows that inflammation during active RA has long-term consequences on molecular remodelling and contractile function of the heart, which further supports that rheumatology patients should be followed for development of heart failure.",
keywords = "cardiac risk factors and prevention, heart disease, heart failure, myocardial disease basic science, translational cardiovascular science",
author = "Gianluigi Pironti and Alex Bersellini-Farinotti and Agalave, {Nilesh M.} and K. S{\'a}ndor and Teresa Fernandez-Zafra and Alexandra Jurczak and Lund, {Lars H.} and Svensson, {Camilla I.} and Andersson, {Daniel C.}",
year = "2018",
month = "5",
day = "26",
doi = "10.1136/heartjnl-2018-312979",
language = "English",
journal = "Heart",
issn = "1355-6037",
publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Cardiomyopathy, oxidative stress and impaired contractility in a rheumatoid arthritis mouse model

AU - Pironti, Gianluigi

AU - Bersellini-Farinotti, Alex

AU - Agalave, Nilesh M.

AU - Sándor, K.

AU - Fernandez-Zafra, Teresa

AU - Jurczak, Alexandra

AU - Lund, Lars H.

AU - Svensson, Camilla I.

AU - Andersson, Daniel C.

PY - 2018/5/26

Y1 - 2018/5/26

N2 - Objectives: Patients with rheumatoid arthritis (RA) display an increased risk of heart failure independent of traditional cardiovascular risk factors. To elucidate myocardial disease in RA, we have investigated molecular and cellular remodelling of the heart in an established mouse model of RA. Methods: The collagen antibody-induced arthritis (CAIA) RA mouse model is characterised by joint inflammation and increased inflammatory markers in the serum. We used CAIA mice in the postinflammatory phase that resembles medically controlled RA or RA in remission. Hearts were collected for cardiomyocyte isolation, biochemistry and histology analysis. Results: Hearts from mice subjected to CAIA displayed hypertrophy (heart/body weight, mean±SD: 5.9±0.8vs 5.1±0.7 mg/g, p<0.05), fibrosis and reduced left ventricular fractional shortening compared with control. Cardiomyocytes from CAIA mice showed reduced cytosolic [Ca2+]i transient amplitudes (F/F0, mean±SD: 3.0±1.2vs 3.6±1.5, p<0.05) that was linked to reductions in sarcoplasmic reticulum (SR) Ca2+ store (F/F0, mean±SD: 3.5±1.3vs 4.4±1.3, p<0.01) measured with Ca2+ imaging. This was associated to lower fractional shortening in the cardiomyocytes from the CAIA mice (%FS, mean±SD: 3.4±2.2 vs 4.6%±2.3%, p<0.05). Ca2+ handling proteins displayed oxidation-dependent posttranslational modifications that together with an increase in superoxide dismutase expression indicate a cell environment with oxidative stress. Conclusions: This study shows that inflammation during active RA has long-term consequences on molecular remodelling and contractile function of the heart, which further supports that rheumatology patients should be followed for development of heart failure.

AB - Objectives: Patients with rheumatoid arthritis (RA) display an increased risk of heart failure independent of traditional cardiovascular risk factors. To elucidate myocardial disease in RA, we have investigated molecular and cellular remodelling of the heart in an established mouse model of RA. Methods: The collagen antibody-induced arthritis (CAIA) RA mouse model is characterised by joint inflammation and increased inflammatory markers in the serum. We used CAIA mice in the postinflammatory phase that resembles medically controlled RA or RA in remission. Hearts were collected for cardiomyocyte isolation, biochemistry and histology analysis. Results: Hearts from mice subjected to CAIA displayed hypertrophy (heart/body weight, mean±SD: 5.9±0.8vs 5.1±0.7 mg/g, p<0.05), fibrosis and reduced left ventricular fractional shortening compared with control. Cardiomyocytes from CAIA mice showed reduced cytosolic [Ca2+]i transient amplitudes (F/F0, mean±SD: 3.0±1.2vs 3.6±1.5, p<0.05) that was linked to reductions in sarcoplasmic reticulum (SR) Ca2+ store (F/F0, mean±SD: 3.5±1.3vs 4.4±1.3, p<0.01) measured with Ca2+ imaging. This was associated to lower fractional shortening in the cardiomyocytes from the CAIA mice (%FS, mean±SD: 3.4±2.2 vs 4.6%±2.3%, p<0.05). Ca2+ handling proteins displayed oxidation-dependent posttranslational modifications that together with an increase in superoxide dismutase expression indicate a cell environment with oxidative stress. Conclusions: This study shows that inflammation during active RA has long-term consequences on molecular remodelling and contractile function of the heart, which further supports that rheumatology patients should be followed for development of heart failure.

KW - cardiac risk factors and prevention

KW - heart disease

KW - heart failure

KW - myocardial disease basic science

KW - translational cardiovascular science

UR - http://www.scopus.com/inward/record.url?scp=85048132827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048132827&partnerID=8YFLogxK

U2 - 10.1136/heartjnl-2018-312979

DO - 10.1136/heartjnl-2018-312979

M3 - Article

C2 - 29804097

AN - SCOPUS:85048132827

JO - Heart

JF - Heart

SN - 1355-6037

ER -