Chronic Caffeine Administration Attenuates Vascular Injury-Induced Neointimal Hyperplasia in Rats

Abstract

Background: Inflammation is considered to be a major initiator to angioplasty-induced vascular restenosis. Proinflammatory cytokines stimulate vascular smooth muscle cell (VSMC) migration and proliferation leading to neointimal hyperplasia. It has been reported that chronic caffeine use suppresses the production of proinflammatory cytokine TNF-a (tumor necrosis factor Alpha) and alters adenosine receptor expression in human neutrophils, indicating that caffeine may attenuate vascular injury-induced inflammation and subsequent neointimal hyperplasia. Our current study was designed to test the hypothesis that chronic caffeine treatment decreases vascular injuryinduced neointimal hyperplasia by suppressing VSMC migration and proliferation. Methods and Results: The experiments were carried out using both in vivo (rat carotid artery injury model) and in vitro (VSMCs isolated from rat aorta) models. Male Sprague-Dawley rats that received chronic caffeine treatment (10 and 20 mg/kg per day, through oral gavage) showed a significant decrease in neointimal hyperplasia when compared to rats that received vehicle. To understand the underlying mechanisms, we tested if caffeine inhibits fetal bovine serum (FBS)-induced VSMC migration and proliferation. We found that caffeine substantially suppressed FBS-induced VSMC migration and proliferation. The attenuation of FBS-stimulated cell migration is dose dependent. Conclusion: Together, our results suggest that chronic treatment with high concentrations of caffeine attenuates vascular injury-induced neointimal hyperplasia by suppressing smooth muscle cell migration and proliferation in rats.

Caffeine prevents restenosis and inhibits vascular smooth muscle cell proliferation through the induction of autophagy

“…VSMC proliferation has been associated with intimal thickening, inflammation, foam cell formation, pathological angiogenesis, and calcification [26][27][28][29] . It previously was suggested that caffeine may inhibit the cell proliferation of VSMCs 13,14 . In order to determine whether caffeine could decrease AoSMC restenosis in vivo, we employed an in vivo mouse model of mechanical de-endothelialization, which mimics the restenosis process.…”

“…First, caffeine facilitates the recruitment of bone marrow endothelial progenitor cells and their nitric oxide production 12,11 to promote vascular repair after mechanical injury. Second, caffeine inhibits the proliferation of VSMCs and decreases restenosis 13,14 . However, the mechanisms involved in these processes are not known.…”