Felodipine attenuates vascular inflammation in a fructose-induced rat model of metabolic syndrome via the inhibition of NF-κB activation¹

Abstract

Aim: Metabolic syndrome is associated with an increased incidence of atherosclerosis. Clinical studies have shown that calcium channel blockers (CCB) inhibit the progression of atherosclerosis. However, the underlying mechanism is unclear. We investigated the inhibitory effect of felodipine on adhesion molecular expression and macrophage infiltration in the aorta of high fructose-fed rats (FFR). Methods: Male Wistar rats were given 10% fructose in drinking water. After 32 weeks of high fructose feeding, they were treated with felodipine (5 mg·kg -1 ·d -1 ) for 6 weeks. The control rats were given a normal diet and water.The aortic expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the infiltration of macrophages were measured by real-time RT-PCR and/or immunohistochemistry. NF-κB activity was measured by electrophoretic mobility shift assay (EMSA). Results: After 32 weeks of high fructose feeding, FFR displayed increased body weight, systolic blood pressure (SBP), serum insulin, and triglycerides when compared with the control rats. The aortic expressions of ICAM-1 and VCAM-1 were significantly increased in FFR than in the control rats and accompanied by the increased activity of NF-κB. FFR also showed significantly increased CD68-positive macrophages in the aortic wall. After treatment with felodipine, SBP, serum insulin, and the homeostasis model assessment decreased significantly. In addition to reducing ICAM-1 and VCAM-1, felodipine decreased macrophages in the aortic wall. EMSA revealed that felodipine inhibited NF-κB activation in FFR. Conclusion: Felodipine inhibited vessel wall inflammation. The inhibition of NF-κB may be involved in the modulation of vascular inflammatory response by CCB in metabolic syndrome.

Fructose induces prothrombotic phenotype in human endothelial cells

“…Since we have previously demonstrated that different stimuli are able to up-regulate TF expression via NF-jB [20,21] and given the property of fructose to induce gene target expression through NF-jB activation [24], we investigated whether fructose-mediated TF up-regulation was determined by NF-jB activation. Thus, we analyzed NF-jB activity in HUVEC cells transfected with a plasmid containing a luciferase reporter gene downstream the promoter region of immunoglobulin j light chain responsive to NF-jB activity and incubated them with fructose.…”

Role of T Regulatory Lymphocytes in the Pathogenesis of High-Fructose Diet–Induced Metabolic Syndrome

“…20 Our study demonstrates that a high-fructose diet can enhance vascular inflammation, which plays a role in vascular injury and ultimately in hypertension. 5 Using Wistar rats fed 10% fructose in drinking water for 38 weeks, Tan et al 40 …”

“…Using Wistar rats fed 10% fructose in drinking water for 38 weeks, Tan et al 40 showed increased expression of adhesion molecules vascular cell adhesion molecule 1 and intercellular adhesion molecule 1, as well as infiltration of monocyte/ macrophages in the aortic wall. Our results have demonstrated increased expression of vascular cell adhesion molecule 1 and platelet endothelial cell adhesion molecule 1 in the aorta of rats fed a high-fructose diet for 5 weeks.…”

Decreased Connexin 43 and Increased Fibrosis in Atrial Regions Susceptible to Complex Fractionated Atrial Electrograms

“…Immunohistochemistry analysis for Cx43 was performed in tissue samples from LA as described previously [16], using mouse monoclonal anti-Cx43 (BD Biosciences). Histopathological slides were analyzed by use of a computer-assisted morphometric analysis system (Image-Pro Plus 5.0).…”