Abstract | INTRODUCTION: Recent studies revealed that co-morbidity and mortality due to cardiovascular disease are increased in patients with rheumatoid arthritis (RA) but little is known about factors involved in these manifestations. This study aimed at characterizing the impact of arthritis on oxidative stress status and tissue fibrosis in the heart of rats with adjuvant-induced arthritis (AIA). METHODS: RESULTS: Compared to controls, AIA rats showed significant 55 and 30% increase of 4-HNE/ protein adducts in serum and left ventricular (LV) tissues, respectively. Cardiac mitochondrial NADP+-isocitrate dehydrogenase (mNADP-ICDH) activity decreased by 25% in AIA rats without any changes in its protein and mRNA expression. The loss of mNADP-ICDH activity was correlated with enhanced accumulation of HNE/mNADP-ICDH adducts as well as with decrease of glutathione and NADPH. Angiotensin II type 1 receptor (AT1R) expression and tissue fibrosis were induced in LV tissues from AIA rats. In isolated cardiomyocytes, HNE significantly decreased mNADP-ICDH activity and enhanced type I collagen and connective tissue growth factor expression. The oral administration of ramipril significantly reduced HNE and AT1R levels and restored mNADP-ICDH activity and redox status in LV tissues of AIA rats. The protective effects of this drug were also evident from the decrease in arthritis scoring and inflammatory markers. CONCLUSION:
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Authors | Qin Shi, Jamilah Abusarah, Ghayath Baroudi, Julio C Fernandes, Hassan Fahmi, Mohamed Benderdour |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 14
Issue 5
Pg. R223
(Oct 18 2012)
ISSN: 1478-6362 [Electronic] England |
PMID | 23079082
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aldehydes
- Angiotensin-Converting Enzyme Inhibitors
- Tumor Necrosis Factor-alpha
- 4-hydroxy-2-nonenal
- Dinoprostone
- Ramipril
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Topics |
- Aldehydes
(metabolism, pharmacology)
- Angiotensin-Converting Enzyme Inhibitors
(pharmacology, therapeutic use)
- Animals
- Arthritis, Experimental
(drug therapy, metabolism, pathology)
- Arthritis, Rheumatoid
(drug therapy, metabolism, pathology)
- Cells, Cultured
- Dinoprostone
(blood)
- Disease Models, Animal
- Female
- Fibrosis
(prevention & control)
- Lipid Peroxidation
(drug effects)
- Mitochondria, Heart
(drug effects, metabolism)
- Myocardium
(pathology)
- Myocytes, Cardiac
(drug effects, metabolism)
- Oxidative Stress
(drug effects)
- Ramipril
(pharmacology, therapeutic use)
- Rats
- Rats, Inbred Lew
- Tumor Necrosis Factor-alpha
(blood)
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