ABSTRACT
PURPOSE: Telmisartan, an angiotensin II receptor blocker (ARB), also acts as an activator of peroxisome proliferator-activated receptor-gamma (PPAR-gamma; PPAR-γ). Several studies have explored the PPAR-γ-endothelial nitric oxide synthase (eNOS) pathway associated with improvement of endothelial function by telmisartan. The ability of telmisartan to induce gene expression and protein level of eNOS and PPARγ in adipocytes was investigated. METHODS: Expression of aP2, PPARγ, eNOS and iNOS genes were measured using the quantitative real-time polymerase chain reaction. The changes, at the protein level, were explored by Western blot, which evaluated the native and phosphorylated eNOS forms, eNOS-Ser(1177) and eNOS-Thr(495). RESULTS: Adipocytes, exposed to telmisartan, exhibited an increase in PPARγ gene expression but a decrease in protein level. Nonetheless, after the exposure to telmisartan, eNOS-Ser(1177) phosphorylation, associated with eNOS activity increment, reached its highest value while eNOS-Thr(495) phosphorylation, involved in the inhibition of eNOS activity, showed its lowest value. CONCLUSION: The results suggest that telmisartan preserves eNOS activity via a mechanism that is partially independent of the PPARγ-eNOS pathway in adipocytes.
Subject(s)
Benzimidazoles/pharmacology , Benzoates/pharmacology , Nitric Oxide Synthase Type III/metabolism , PPAR gamma/agonists , 3T3 Cells , Adipocytes/drug effects , Adipocytes/metabolism , Animals , Blotting, Western , Fatty Acid-Binding Proteins/genetics , Fatty Acid-Binding Proteins/metabolism , Mice , Nitrates/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III/genetics , Nitrites/metabolism , PPAR gamma/genetics , Reactive Oxygen Species/metabolism , Real-Time Polymerase Chain Reaction , TelmisartanABSTRACT
Recent genome-wide single nucleotide polymorphism (SNP) association studies (GWAS) have identified a number of SNPs that were significantly associated with coronary artery disease (CAD) and myocardial infarction (MI). We tested for replication of the previously described association with CAD in our case-control datasets of SNPs variants located at 1p13.1, 2q33.1, 10q11.1, 9p21, and 21q22. We observed a small significant risk associated of the SNP rs10757274 with CAD in the PROCAGENE study. Besides, the multilocus combination rs10757274 and rs1333048 gave a near significant result. We confirmed that the SNP rs10757274 showed association with CAD in the PROCAGENE study, although after applying the Bonferroni correction was not longer significant. Independent replication studies in other populations are needed to unequivocally confirm the association.
