Abstract
Atherosclerosis is the most prevalent disease in middle and later years of human life. Heart attacks and strokes are among the most frequent causes of death. New approaches in therapy are the use of NSAID’s (nonsteroidal antiphlogistical drugs) of the new generation (selective inhibitors of COX-2) and DHEA (Dehydroepiandrostenon). The key enzyme of prostaglandin synthesis, the COX-2 isoenzyme, is predominantly found in inflammatory tissue. Out of this results a possible importance of COX-2-inhibitors in prophylaxis of atherosclerosis. Our study intended to examine the significance of COX-2 and the COX-2-formed prostanoids, as well as the significance of COX-2-independent iso-prostanes on atherosclerosis. For that purpose we tested the effect of the selective COX-2-inhibitor Celecoxib on rabbits fed with cholesterol and compared this with the effect of the steroid hormone DHEA in 4 groups: healthy control, cholesterol-fed control, DHEA-group and Celecoxib group. In the test prostanoids, nitrate and nitrite were measured by gas chromatograpy/tandem-mass-spectrometry (GC-MS/MS) in 24-hours-collected urine. Additionally we measured cholesterol and triglycerides in plasma. The aortas of the examinated animals were measured optically using a planimetrical method. The measurement of prostanoids, isoprostanes, nitrate and nitrite showed considerable variations and particulary significant differences (p < 0.01) even in the initial values. By the treatment with Celecoxib the rate of atherosclerosis was reduced in a highly significant way in comparison to the cholesterol group and the DHEA-group. Consequently the test demonstrated a significant role of COX-2 in the development of atherogenesis.
Highlights
Atherosclerosis is one of the most frequent diseases in middle aged and elder humans
Under medication with the steroid hormone DHEA a significant reduction of plaque size was proven in an animal model [6,7,8,9]
In our study we were able to demonstrate that COX-2 plays a considerable role in the mechanisms of atherosclerosis, as a statistically highly significant reduction of the rate of atherosclerosis was achieved through treatment with the COX-2 inhibitor Celecoxib
Summary
Atherosclerosis is one of the most frequent diseases in middle aged and elder humans. Two of the new approaches are the treatment with NSAID’s of the new generation and the treatment with the steroid hormone DHEA [2,3,4,5]. Under medication with the steroid hormone DHEA a significant reduction (up to 50% compared to the control group) of plaque size was proven in an animal model [6,7,8,9]. Non-steroidal antiinflammatory drugs lead to a significant reduction of the atherosclerosis rate in a model with rabbits [6]. The inhibition of the proinflammatory synthesis of prostanoids in the vascular wall is discussed as a possible anti-atherosclerotic mechanism of NSAID’s [9]. COX-1 is responsible for the physiological synthesis of prostanoids. COX-2, is expressed under influence of cytokines or endotoxin, so it is mainly found in inflammatory tissue [10,11,12]
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