COX-2 inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common treatment for chronic inflammatory diseases like arthritis and atherosclerosis.
The objectives of this study were: a) to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2), thromboxane A2 (TXA2) and endothelin-1 (ET-1) to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b) to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction.
Cyclooxygenase-2 (COX-2), a key synthase in prostaglandin pathways, displays high density in atherosclerotic lesions and promotes early atherosclerosis in CAD progression.
In addition, real-time quantitative RT-PCR analyses showed that the apoA-I infusions decreased the mRNA levels of two pro-inflammatory molecules, i.e. nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2), in aorta of AS rabbits, which was associated with a concomitant reduction in endothelial VCAM-1 and IL-6 mRNA transcription.
These deficits are not associated with atherosclerosis but are accompanied with altered astroglial activation, neurogenesis, cyclooxygenase-2 immunoreactivity and increased plasma IL-6.
In the present study we analyzed whether COX-2 gene variants associate independently with the early subclinical markers of atherosclerosis, carotid intima-media thickness and carotid artery distensibility in a population of young healthy Caucasian adults.
We also examined whether SHXXT can influence the production of several biomarkers of inflammation and atherosclerosis including reactive oxygen species (ROS), COX-2, ERK1/2, IL-1β, IL-6, IL-8 and MCP-1.
Inflammatory mediators, including prostanoids produced by inducible cyclooxygenase-2 (COX-2), play a significant role in the development of atherosclerosis.
Inhibition of 11betaHSD2 did not reduce systemic prostacyclin production or accelerate atherosclerosis in mice, thereby avoiding the major cardiovascular side effects seen with systemic COX-2 inhibitors.
A secondary aim was to replicate the interaction of PTGS2rs20417 (-765G to C) with aspirin use on coronary heart disease risk observed in the Atherosclerosis Risk in Communities Study (ARIC).
We conclude that for haploinsufficient mutants, such as the R212C, the enhanced atherothrombotic phenotype is likely dependent on the presence of existing atherosclerosis or injury (high risk factors), analogous to what has been observed in the cyclooxygenase-2 inhibition studies or prostacyclin receptor knockout mice studies.
The present study explored whether the COX-2G-765C polymorphism contributes to increased incidence of coronary heart disease (CHD) or stroke in the large prospective Atherosclerosis Risk in Communities (ARIC) Study.
We genotyped 2212 Atherosclerosis Risk in Communities study participants (1,023 incident coronary heart disease (CHD) cases; 270 incident ischemic stroke cases; 919 non-cases) with available DNA for polymorphisms in PTGS1 and PTGS2.
These results provide that acrolein may play a role in progression of atherosclerosis and new information on the signaling pathways involved in COX-2 upregulation in response to acrolein and provide evidence that PKCdelta and p38 MAPK are required for transcriptional activation of COX-2.
In asymptomatic hypercholesterolemic subjects the C allele of -765G>C COX-2 polymorphism was associated with lower COX-2 expression, and reduced subclinical atherosclerosis and systemic inflammation compared with GG homozygous, thus conferring atherosclerosis protection in this cardiovascular risk population.
In asymptomatic hypercholesterolemic subjects the C allele of -765G>C COX-2 polymorphism was associated with lower COX-2 expression, and reduced subclinical atherosclerosis and systemic inflammation compared with GG homozygous, thus conferring atherosclerosis protection in this cardiovascular risk population.
Through screening expression patterns of typical genes involved in atherosclerosis and foam cell generation, we could demonstrate that mRNA levels of cyclooxygenase-2, interleukin 1beta, and tumor necrosis factor-alpha were increased in a time- and dose-dependent manner in U937 macrophages treated with TCDD, like oxLDL, and that these changes accompanied significantly elevated levels of matrix-degrading metalloproteinases (MMP)-1, MMP-3, MMP-12, and MMP-13.
These results support the potential of antiinflammatory approaches for the prevention of atherosclerosis and identify cyclooxygenase-2 as a target for intervention.
the expression of COX-2 by inflammatory and vascular cells in atherosclerotic arteries suggests that products of this enzyme may be important in the pathogenesis of atherosclerosis.