Caffeine Enhances Endothelial Repair by an AMPK-Dependent Mechanism

Abstract

Objective-Migratory capacity of endothelial progenitor cells (EPCs) and mature endothelial cells (ECs) is a key prerequisite for endothelial repair after denuding injury or endothelial damage. Methods and Results-We demonstrate that caffeine in physiologically relevant concentrations (50 to 100 mol/L) induces migration of human EPCs as well as mature ECs. In patients with coronary artery disease (CAD), caffeinated coffee increased caffeine serum concentration from 2 mol/L to 23 mol/L, coinciding with a significant increase in migratory activity of patient-derived EPCs. Decaffeinated coffee neither affected caffeine serum levels nor migratory capacity of EPCs. Treatment with caffeine for 7 to 10 days in a mouse-model improved endothelial repair after denudation of the carotid artery. The enhancement of reendothelialization by caffeine was significantly reduced in AMPK knockout mice compared to wild-type animals. Transplantation of wild-type and AMPK Ϫ/Ϫ bone marrow into wild-type mice revealed no difference in caffeine challenged reendothelialization. ECs which were depleted of mitochondrial DNA did not migrate when challenged with caffeine, suggesting a potential role for mitochondria in caffeine-dependent migration. Conclusion-These results provide evidence that caffeine enhances endothelial cell migration and reendothelialization in part through an AMPK-dependent mechanism, suggesting a beneficial role for caffeine in endothelial repair.

Two Isoforms of Sister-of-Mammalian Grainyhead Have Opposing Functions in Endothelial Cells and In Vivo

“…To assess the impact of the 2 transcription factor isoforms on EC migration, we expressed SOM1 or SOM3 in primary human EC ( Figure 1A) and determined their migratory capacity by setting an artificial wound in the EC monolayer and counting the migrated cells. 11 As shown in Figure 1B and 1C, SOM1 dramatically induced migration, whereas SOM3 significantly reduced the migratory capacity of EC after 24 hours. These effects were not attributable to enhanced or reduced proliferation of the cells ( Figure II in the online-only Data Supplement).…”

Exercise partially reverses the inhibitory effect of caffeine on liver gluconeogenesis in type 1 diabetic rats with hypoglycemia

“…However, in other cases, in spite of not having nutritional value, caffeine has been used as an ergogenic substance because it improves performance in long-term physical activities. The ergogenic effect of caffeine is reversible and seems to be mediated by central and peripheral mechanisms of action that can trigger physiological and metabolic changes (19,38,40,44). At first, the action of caffeine was linked to an increase in the serum concentration of adrenaline and noradrenaline, which would lead to the enhanced oxidation of free fatty acids and saving of glycogen by the muscle tissue (9,19,25,38,40,44), but adenosine receptor antagonism seems to be the major mechanism of action of caffeine (4).…”

Consumption of a boiled Greek type of coffee is associated with improved endothelial function: The Ikaria Study

“…[28][29][30][31] Caffeine (1,3,7-trimethylxanthine) is the most important and well-known pharmacologic compound of it, acting as a competitive inhibitor of cyclic nucleotide phosphodiesterase isoenzymes and exerting various functions including the modulation of glucose metabolism, alterations in apoptotic processes, immunomodulatory effects, and stimulation of muscle contraction. 9 Acute and chronic coffee intake is associated with increased arterial stiffness and wave reflections in healthy subjects and in hypertensive ones. 32,33 Moreover, caffeine intake acutely increases blood pressure 34 and postprandial glucose levels in diabetics subjects -probably due to the increase of catecholamine released.…”

“…8 Furthermore, caffeine enhances endothelial cell migration and re-endothelialization, partly through an AMP protein kinase-dependent mechanism, suggesting a beneficial role of caffeine on endothelial repair. 9 Interestingly, chlorogenic acid, a polyphenol found in coffee, with its metabolites (caffeic and ferulic acids) have beneficial antihypertensive effects. 48,49 The antihypertensive effect of chlorogenic acid is reported to be associated with NO, as caffeic and ferulic acids appear to improve vascular function by reducing reactive oxygen species production and enhancing the bioavailability of NO.…”

“…6,7 Moreover, favorable effects of chronic caffeine administration on endothelial cell migration, on re-endothelialization and on the expression of nitric oxide synthase enzyme have also been reported. 8,9 It is known that endothelium plays a key role in vascular function and parameters of vascular function and structure show important clinical impact and are associated with cardiovascular risk. [10][11][12] Endothelial function, which is usually quantified by flow-mediated dilatation (FMD) in the brachial artery, 13 reflects the 'health' of the vessel wall and is affected by various lifestyle habits (e.g.…”