Thus our findings suggest that ZINC72348892 and ZINC72295579 as promising lead molecules for inhibition of COX-2 and which would provide alternative chemotypes in the drug discovery pipeline for the treatment of cardiovascular diseases.AbbreviationsCVDsCardiovascular diseasesCOXCyclooxygenaseMDMolecular dynamicsMM/PBSAMolecular mechanics Poisson-Boltzmann surface areaROFRule of fiveNVTNumber of particles, volume and temperatureNPTNumber of particles, pressure and temperatureRMSDRoot mean square deviationRMSFRoot mean square fluctuationSASASolvent accessible surface areaRgRadius of gyrationPCAPrincipal component analysisEDEssential dynamicsNHBsNumber of hydrogen bondsCommunicated by Ramaswamy H. Sarma.
This work also warrants an evaluation of high-dose aspirin and COX-2 inhibitor therapy in sufferers of inflammatory conditions who are already at increased risk for cardiovascular disease.-Khan, S. I., Shihata, W. A., Andrews, K. L., Lee, M. K. S., Moore, X.-L., Jefferis, A.-M., Vinh, A., Gaspari, T., Dragoljevic, D., Jennings, G. L., Murphy, A. J., Chin-Dusting, J. P. F. Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat.
Over expression of cyclooxygenase-2 (COX-2) enzyme is associated with various physical disorders like various types of inflammations associated with cardiovascular diseases or malignancies.
Given the cardiovascular hazard of a COX-2 inhibitor, our findings indicate that the EP3 receptor and its downstream pathways may be potential targets for prevention of TCDD-associated cardiovascular diseases.
Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases.
The allele -765C, of the -765G > C polymorphism (rs20417) in the COX-2 promoter has lower promoter activity compared with the -765G allele and protective effects in cardiovascular disease.
Cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) are enzymes involved in prostaglandin and prostacyclin synthesis, which have been linked to cardiovascular disease risk.
We sought to determine if variants in the COX-2 gene were associated with subclinical measures of cardiovascular disease in a primarily type 2 diabetic population.
We assessed the -765G>C polymorphism and COX-2 expression in 220 asymptomatic subjects free ofcardiovascular disease, in relation to global vascular risk, carotid intima-media thickness (IMT), and inflammatory markers (fibrinogen, C-reactive protein [CRP], von Willebrand factor [vWF] and interleukin-6 [IL-6]).
We evaluated two PTGS2 (rs20417, rs689470), and three PTGER2 (rs708494/uS5, rs708495/uS7, and chr14: 50 764 013/uS10) gene polymorphisms among 600 Caucasian male participants of the Physicians' Health Study with incident myocardial infarction (MI) or ischemic stroke and 600 age- and smoking-matched controls who remained free of all reported cardiovascular disease.
The recent progress sheds light on the pathophysiological mechanisms of COX-2 and new transcription-based strategy for controlling COX-2 overexpression and COX-2-mediated cardiovascular diseases.