Telmisartan-induced eNOS gene expression is partially independent of its PPAR-gamma agonist property

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. e 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. e changes, at the protein level, were explored by Western blot, which evaluated the native and phosphorylated eNOS forms, eNOS-Ser 1177 and eNOS-r 495 .Results: Adipocytes, exposed to telmisartan, exhibited an increase in PPARγ gene expression but a decrease in protein level. Nonetheless, a er the exposure to telmisartan, eNOS-Ser 1177 phosphorylation, associated with eNOS activity increment, reached its highest value while eNOS-r 495 phosphorylation, involved in the inhibition of eNOS activity, showed its lowest value.Conclusion: e results suggest that telmisartan preserves eNOS activity via a mechanism that is partially independent of the PPARγ-eNOS pathway in adipocytes.

Kmup-1 Protects Kidney from Streptozotocin-Induced Pro-Inflammation in Early Diabetic Nephropathy by Restoring Enos/Pparγ and Inhibiting MMP-9

“…KMUP-l might function as an antioxidant eNOS activator via PPARy, preventing from worsening by ROS. KMUP-I, characterized with an ability to increase eNOS/PPARy, is suggested to be useful for slowing down the progressing of ON (17,21).…”

“…Peroxisome proliferator-activated receptors (PPARs) are found in all mammalian species and each subclass has unique tissue specificity and functions (17), among which PPARy agonist has been used in the control of diabetic disease. Moreover, eNOS/ PPARy is involved in inhibiting ON (18).…”

KMUP-1, a GPCR Modulator, Attenuates Triglyceride Accumulation Involved MAPKs/Akt/PPARγ and PKA/PKG/HSL Signaling in 3T3-L1 Preadipocytes

“…Notably, the unique PDE inhibitor KMUP-1, which activates PKA and PKG, partly shares a similar mechanism of action in 3T3-L1 preadipocytes. Additionally, PPARγ, a regulator of lipid metabolism, is expressed in 3T3-L1 preadipocytes [ 9 , 13 ]. Inhibition of PDE5 and PDE3B induce adipocyte lipolysis by cGMP/PKG and cAMP/PKA elevation [ 14 , 15 ].…”