Pycnogenol attenuates atherosclerosis by regulating lipid metabolism through the TLR4-NF-kappaB pathway

Atherosclerosis is a leading cause of death worldwide and is characterized by lipid-laden foam cell formation. Recently, pycnogenol (PYC) has drawn much attention because of its prominent effect on cardiovascular disease (CVD). However, its protective effect against atherosclerosis and the underlying mechanism remains undefined. Here PYC treatment reduced areas of plaque and lipid deposition in atherosclerotic mice, concomitant with decreases in total cholesterol and triglyceride levels and increases in HDL cholesterol levels, indicating a potential antiatherosclerotic effect of PYC through the regulation of lipid levels. Additionally, PYC preconditioning markedly decreased foam cell formation and lipid accumulation in lipopolysaccharide (LPS)-stimulated human THP-1 monocytes. A mechanistic analysis indicated that PYC decreased the lipid-related protein expression of adipose differentiation-related protein (ADRP) and adipocyte lipid-binding protein (ALBP/aP2) in a dose-dependent manner. Further analysis confirmed that PYC attenuated LPS-induced lipid droplet formation via ADRP and ALBP expression through the Toll-like receptor 4 (TLR4) and nuclear factor-kappaB (NF-kappaB) pathway, because pretreatment with anti-TLR4 antibody or a specific inhibitor of NF-kappaB (PDTC) strikingly mitigated the LPS-induced increase in ADRP and ALBP. Together, our results provide insight into the ability of PYC to attenuate bacterial infection-triggered pathological processes associated with atherosclerosis. Thus PYC may be a potential lead compound for the future development of antiatherosclerotic CVD therapy.

Resveratrol inhibits foam cell formation via NADPH oxidase 1-mediated reactive oxygen species and monocyte chemotactic protein-1

Resveratrol is a polyphenolic compound in red wine that has anti-oxidant and cardioprotective effects in animal models. Reactive oxygen species (ROS) and monocyte chemotactic protein-1 (MCP-1) play key roles in foam cell formation and atherosclerosis. We studied LPS-mediated foam cell formation and the effect of resveratrol. Resveratrol pretreatment strongly suppressed LPS-induced foam cell formation. To determine if resveratrol affected the expression of genes that control ROS generation in macrophages, NADPH oxidase 1 (Nox1) was measured. Resveratrol treatment of macrophages inhibited LPS-induced Nox1 expression as well as ROS generation, and also suppressed LPS-induced MCP-1 mRNA and protein expression. We investigated the upstream targets of Nox1 and MCP-1 expression and found that Akt-forkhead transcription factors of the O class (FoxO3a) is an important signaling pathway that regulates both genes. These inhibitory effects of resveratrol on Nox1 expression and MCP-1 production may target to the Akt and FoxO3a signaling pathways.

Effects of high-carbohydrate and high fat diet on formation of foam cells and expression of TNF-alpha in Rattus novergicus.

AIM: to examine the role of high carbohydrate and high fat diet on formation of foam cells and expression of TNFalpha, an early stage of atherosclerosis. METHOD: three months old male Rattus Novergicus strain Wistar were allocated into 3 groups, normal diet group (GI, n=8), high carbohydrate diet group (GII, n=8), and high fat diet group (G III, n=8). Those groups received an isoenergetic diet but contained different percentage of carbohydrate and fat for 12 weeks. The rest of the food was measured daily to calculate the calorie intake. The body weight was measured weekly. At the end of study, blood samples were taken using cardiac puncture to examine lipid profiles and random blood sugars. RESULTS: levels of blood glucose significantly increased in GII compared to the GI (281.87 +/- 39.66 mg/dl vs 192.5 +/- 1.4 mg/dl, p=0.002). Group II and G III showed increased of triglyseride compared to GI (138.0 +/- 47.15 vs 85.5 +/-20.3, p=0.02; 163.62 +/- 41.77 vs 85.5 +/- 20.3, p=0.00, respectively). Level of LDL significantly increased in G III compared to GI (72 +/- 35.6 vs 27.0 +/- 8.9, p=0.00). No statistical difference in level of HDL among the three groups. Level of TNFalpha significantly increased in GII and G III compared to GI (19.13 +/- 3.68 vs 2.5 +/- 1.4, p=0.00; 23.6 +/- 5.58 vs 2.5 +/- 1.4, p=0.00, respectively). The number of foam cells was significantly increased in GII and G III compared to GI (7.18 +/- 5.28 vs 1.2 +/- 1.4, p=0.00; 9.91 +/- 6.26 vs 1.2 +/- 1.4, p=0.00, respectively). The foam cell had strong correlation with triglyseride level and TNFalpha (r=0.696, p=0.00; r=0.618, p=0.00, respectively). CONCLUSION: this result shows that high carbohydrate and high fat diet potentially increase the risk factor of atherosclerosis. Both diets induced the inflammatory process and increase foam cells formation, are in the early stage of atherosclerosis.