Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rheumatoid arthritis
نویسندگان
چکیده
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 AIA was induced with complete Freund's adjuvant in female Lewis rats. Animals were treated by oral administration of vehicle or angiotensin-converting enzyme inhibitor ramipril (10 mg/kg/day) for 28 days, beginning 1 day after arthritis induction. Isolated adult cardiomyocytes were exposed to 10 μM 4-hydroxynonenal (HNE) for 24 hours in the presence or absence of 10 μM ramipril. 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 Collectively, our findings disclosed that AIA induced oxidative stress and fibrosis in the heart. The fact that ramipril attenuates inflammation, oxidative stress and tissue fibrosis may provide a novel strategy to prevent heart diseases in RA.
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Response to 'Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rheumatoid arthritis'
investi gated the eff ects of ramipril on oxidative stress and fi brosis in the heart of rat s with adjuvant arthritis. Th e authors concluded that ramipril reversed arthritis scoring and decreased markers of oxidative stress, infl ammation, and tissue fi brosis. Undoubtedly, their fi ndings will promote the attempt to diminish the cardiovascular risk of patients with rheumatoid arthritis (RA) ...
متن کاملResponse to 'Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rheumatoid arthritis' - authors' reply
about our recent study [2] and would like to make two points to clarify our reasoning. First, in our study [2], female Lewis rats have been used in order to induce arthritis. Th is experimental model of arthritis was well described in our previous study published in Molecular Th erapy [3]. Actually, a number of researchers use male or female animals to induce arthritis. For example, the use of ...
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