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Liver malignancies include primary and metastatic tumors. Limited progress has been achieved in improving the survival rate of patients with advanced stage liver cancer and who are unsuitable for surgery. Apart from surgery, chemoradiotherapy, trans-arterial chemoembolization and radiofrequency ablation, a novel therapeutic modality is needed for the clinical treatment of liver cancer. Photodynamic therapy (PDT) is a novel strategy for treating patients with advanced cancers; it uses a light-triggered cytotoxic photosensitizer and a laser light. PDT provides patients with a potential treatment approach with minimal invasion and low toxicity, that is, the whole course of treatment is painless, harmless, and repeatable. Therefore, PDT has been considered an effective palliative treatment for advanced liver cancers. To date, PDT has been used to treat hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma and liver metastases. Clinical outcomes reveal that PDT can be considered a promising treatment modality for all liver cancers to improve the quality and quantity of life of patients. Despite the advances achieved with this approach, several challenges still impede the application of PDT to liver malignancies. In this review, we focus on the recent advancements and discuss the future prospects of PDT in treating liver malignancies.

The impact of portal hypertension (PH) on postoperative short-term outcomes and long-term survival in hepatocellular carcinoma (HCC) patients has lately been discussed controversially. This study aimed to explore the influence of PH on postoperative outcomes in HCC patients undergoing surgical resection.Patients undergoing hepatectomy for HCC from 2010 to 2014 were enrolled. The impact of PH on postoperative complications, posthepatectomy liver failure (PHLF) and overall survival (OS) was evaluated.A total of 355 HCC patients were enrolled; 129 (36.3%) experienced postoperative complications and 21 (5.9%) developed PHLF. PH was identified as an independent predictor of PHLF. Patients with PH experienced a higher incidence of complications and PHLF than patients without PH. On the Cox proportional hazards regression model, PH was verified as a risk factor of OS for BCLC stage 0/A and B patients. Patients without PH had significantly better long-term survival compared to patients with PH both in the total cohort and in cirrhosis subgroup.Liver resection in HCC patients with PH showed a significantly increased postoperative complications and PHLF, and revealed a decreasing long-term survival than non-PH patients. Besides, tumor burden also played an important role in determining the OS. However, due to the improvement in surgical technique and perioperative management, surgery was feasible in carefully selected HCC patients with PH.

BACKGROUND Hepatocellular carcinoma (HCC) is the world’s sixth most common malignant tumor and the third cause of cancer death. Although great progress has been made in hepatectomy, it is still associated with a certain degree of risk of post-hepatectomy liver failure (PHLF), which extends the length of hospital stay and remains the leading cause of postoperative death. Studies have shown that assessment of hepatic functional reserve before hepatectomy is beneficial for reducing the incidence of PHLF. AIM To assess the value of model for end-stage liver disease (MELD) score combined with standardized future liver remnant (sFLR) volume in predicting PHLF in patients undergoing hepatectomy for HCC. METHODS This study was attended by 238 patients with HCC who underwent hepatectomy between January 2015 and January 2018. Discrimination of sFLR volume, MELD score, and sFLR/MELD ratio to predict PHLF was evaluated according to the area under the receiver operating characteristic curve. RESULTS The patients were divided into two groups according to whether PHLF occurred after hepatectomy. The incidence of PHLF was 8.4% in our research. The incidence of PHLF increased with the decrease in sFLR volume and the increase in MELD score. Both sFLR volume and MELD score were considered independent predictive factors for PHLF. Moreover, the cut-off value of the sFLR/MELD score to predict PHLF was 0.078 (P < 0.001). This suggests that an sFLR/MELD ≥ 0.078 indicates a higher incidence of PHLF than an sFLR/MELD < 0.078. CONCLUSION MELD combined with sFLR is a reliable and effective PHLF predictor, which is superior to MELD score or sFLR volume alone.

Supplemental Digital Content is available in the text, A precise and noninvasive method to predict posthepatectomy liver failure (PHLF) in clinical practice is still lacking. Liver fibrosis or cirrhosis accompanied with varying degrees of portal hypertension plays an important role in the occurrence of PHLF in hepatocellular carcinoma (HCC) patients. This study aims to compare the predictive ability of the albumin-bilirubin score to spleen thickness ratio (ALBI/ST) versus fibrosis-4 index (FIB-4) and aspartate aminotransferase to platelet count ratio index (ARPI) for the occurrence of PHLF. We retrospectively enrolled 932 patients who underwent liver resection for HCC between 2010 and 2017. The predictive accuracy of ALBI/ST ratio, FIB-4, and APRI for occurrence of PHLF was evaluated by receiver operating characteristic curve analysis. PHLF was diagnosed in 69 (7.4%) patients. The ALBI/ST ratio was found to be a significant predictor of PHLF. The AUC of ALBI/ST (AUC = 0.774; 95% CI, 0.731–0.817; P

The Child-Pugh (CP) score is a widely used method to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the fibrosis index (FIB-4) has been demonstrated to be closely associated with liver fibrosis and cirrhosis. This study aimed to compare the capability of FIB-4 index with CP score in predicting the outcomes for HCC patients after hepatectomy. A total of 495 HCC patients who underwent hepatectomy were enrolled. The performance of the FIB-4 index in predicting postoperative liver failure (PHLF) and overall survival was compared with that of the CP score. Of them, 9.3% (46/495) patients developed PHLF. The area under the receiver operating characteristic (ROC) curve of the FIB-4 index for predicting PHLF was greater than that of the CP score (0.744 versus 0.621; P = 0.044). The optimal cutoff value of the FIB-4 index for predicting PHLF was 4.16. Multivariable analyses revealed that the FIB-4 index was an independent predictor of PHLF regardless of the hepatectomy subgroups, but the CP grade was only a significant predictor of PHLF in the minor hepatectomy subgroup. The FIB-4 index (4.16) stratified patients into two distinct overall survival cohorts (P = 0.006). The FIB-4 index also classified patients with the Barcelona Clinical Liver Cancer (BCLC) stages 0 and A into two distinct overall survival cohorts (P = 0.001 and P = 0.034, respectively). The FIB-4 index may be a better predictor of PHLF and overall survival in HCC patients with hepatectomy than CP score.

Background Underlying liver function is a major concern when applying surgical resection for hepatocellular carcinoma (HCC). We aimed to explore the capability of the albumin-bilirubin (ALBI) grade to predict post-hepatectomy liver failure (PHLF) and long-term survival after hepatectomy for HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stages. Methods Between January 2010 and December 2014, 338 HCC patients who were treated with liver resection were enrolled. The predictive accuracy of ALBI grade system for PHLF and long-term survival across different BCLC stages was examined. Results A total of 26 (7.7%) patients developed PHLF. Patients were divided into BCLC 0/A and BCLC B/C categories. ALBI score was found to be a strong independent predictor of PHLF across different BCLC stages by multivariate analysis. In terms of overall survival (OS), it exhibited high discriminative power in the total cohort and in BCLC 0/A subgroup. However, differences in OS between ALBI grade 1 and 2 patients in BCLC B/C subgroup were not significant (P = 0.222). Conclusion The ALBI grade showed good predictive ability for PHLF in HCC patients across different BCLC stages. However, the ALBI grade was only a significant predictor of OS in BCLC stage 0/A patients and failed to predict OS in BCLC stage B/C patients. Electronic supplementary material The online version of this article (10.1186/s12957-018-1500-9) contains supplementary material, which is available to authorized users.

Background: CD4+CD25+FoxP3+ regulatory T cells (Treg cells) play a protective role against the development and progression of the inflammatory disease atherosclerosis (AS). MicroRNA-21 (miR-21) is expressed in Treg cells and is up-regulated in the context of AS and other inflammatory diseases. Aims: This study aimed to determine the role of miR-21 in Treg cell regulation and gene expression during the development of AS in patients with coronary heart disease (CHD). Methods and Results: MiR-21 expression in peripheral blood mononuclear cells (PBMCs) was significantly up-regulated in patients with CHD (acute myocardial infarction (AMI) group, n=24; unstable angina (UA) group, n=21; stable angina (SA) group, n=24) compared with patients with chest pain syndrome (CPS, n=27), and miR-21 expression showed an increasing trend from SA to UA to AMI patients. Moreover, flow cytometry analysis indicated that the frequencies of circulating Treg cells decreased in a manner proportionate opposite with the level of miR-21. Quantitative real-time PCR (qRT-PCR) revealed a decrease in mRNA expression of forkhead box P3 (foxp3), transforming cell growth factor beta 1(TGF-β1) and smad7 (a known target gene of miR-21). ELISA analysis revealed a decrease in TGF-β1 secreted into the plasma. In addition, we transfected PBMCs with a miRNA negative control (NS-m), a miR-21 mimic (miR-21-m), a miRNA inhibitor negative control (NS-i), or a miR-21 inhibitor(miR-21-i). Up-regulation of miR-21 decreased the frequency of circulating Treg cells, decreased the expression levels of foxp3, TGF-β1 and smad7, and decreased the amount of TGF-β1 secreted into the plasma. Consistent with these observations, miR-21 down-regulation increased the frequency of circulating Treg cells, increased the expression of foxp3, TGF-β1 and smad7, and increased the amount of TGF-β1 secreted into the plasma. Conclusions: Because the smad7 expression pattern was similar to that of TGF-β, our study suggests that miR-21 can negatively regulate the frequency of circulating Treg cells through a TGF-β1/smad-independent signaling pathway in PBMCs.

Interleukin-27 (IL-27) is an important cytokine in inflammatory diseases, including coronary artery disease (CAD). To explore the precise role of IL-27 in CAD, we investigated the genetic association between IL27 and CAD in the GeneID Chinese Han population. A two-stage case control association analysis was performed for 3075 CAD cases and 2802 controls. Logistic regression analysis was used to adjust the traditional risk factors for CAD. Results showed that a promoter variant, rs153109, tended to be marginally associated with CAD in the discovery population (Padj = 0.028, OR = 1.27, 95%CI: 1.03–1.58). However, this association was not replicated in the validation stage (Padj = 0.559, OR = 1.04, 95%CI: 0.90–1.21). In addition, when we classified the combined population into two subgroups according to the age at disease onset or disease state, we again obtained no significant associations. Finally, we estimated the severity of coronary stenosis using the Gensini Scoring system and determined that the rs153109 genotypes were still not associated with the Gensini scores of the CAD patients. In conclusion, our study failed to find an association between common variants in the functional region of IL27 and CAD in a Chinese Han population, which indicated that IL-27 might only be an inflammatory marker during the development of CAD.

To determine the effects of interleukin (IL)-17A inhibition on experimental atherosclerosis.ApoE(-/-) mice were treated with either rat anti-mouse IL-17A, mouse anti-mouse IL-17A or isotype-matched control antibodies for 12 weeks (n=8-10 per group). Ldlr(-/-) mice were transplanted with IL-17A-deficient or wild type bone marrow (n=8 per group). Rat anti-mouse IL-17A treatment obviously reduced plaque size by 43% (p0.01) without evidence of reduced IL-17A signaling. In contrast, mouse anti-mouse IL-17A treatment and IL-17A deficiency in bone marrow cells did not alter lesion size despite significant reduction of IL-17A production.Inhibition of IL-17A signaling does not alter lesion development in Th1-biased C57BL/6 ApoE(-/-) and Ldlr(-/-) mice with already low levels of IL-17A production. Alteration of lesion development after repeated injections of rat anti-mouse IL-17A antibody in ApoE(-/-) mice could not be attributed to blockade of IL-17A signaling.

Atherosclerosis is a chronic inflammatory disease in which the renin-angiotensin-aldosterone system plays an important role. Evidence indicate that the angiotensin type 1 receptor blockers can suppress atherogenesis, but the exact mechanisms have not been fully elucidated. The study was undertaken to investigate the potential effects and molecular mechanisms of an angiotensin type 1 receptor blocker irbesartan on atherogenesis in high cholesterol-diet apolipoprotein E knock-out mice.Adult male apolipoprotein E knock-out mice were given normal diet or high cholesterol-diet and randomized to receive no treatment or irbesartan 10 mg kg(-1) d(-1) for 12 weeks. The apolipoprotein E knock-out mice with high cholesterol-diet were associated with a marked increase in atherosclerotic lesion area, plasma lipid and angiotensin II levels, as well as the expressions of angiotensin type 1 receptor in the aorta. High cholesterol-diet feeding increases the activity of NADPH oxidase subunits (p47(phox) and Rac), extracellular signal-regulated kinase 1/2, janus kinase 2, signal transducer and activator of transcription 3, nuclear factor-kappaB and the expression of tumor necrosis factor-alpha, interleukin 6, monocyte chemoattactant protein-1 and vascular cell adhesion molecule-1 in the aortas. These changes were suppressed in mice that were treated with irbesartan 10 mg kg(-1) d(-1), with no significant change in systolic blood pressure and plasma lipid levels.The results suggest that irbesartan can attenuate atherosclerosis, and this effect is partly related to the inhibition of oxidative stress and inflammatory signal transduction pathways which eventually leads to the decrease in the expression of inflammatory cytokines.

Aim Hyperhomocysteinemia (Hhcy) is an important and independent risk factor for atherosclerosis. Recent studies have shown that Poly (ADP-ribose) polymerase (PARP) activation may be associated with Hhcy-induced endothelial dysfunction, which is an important mechanism for Hhcy to affect atherosclerotic progress. Thus, we investigated whether PARP inhibitors may attenuate atheroscle-rotic plaque development in an Hhcy-induced experimental animal model with atherosclerosis. Methods Six-week-old homozygous apolipoprotein E-deficient (ApoE-/-) male mice fed a normal diet or high methionine diet randomly received intraperitoneal injections of 10 mg/kg 3-aminoben-zamide (3-AB, a PARP inhibitor) dissolved in phosphate-buffered saline (PBS), or physiological saline every other day for 12 weeks. Atherosclerotic lesion sizes and PARP activity were measured. Related inflammatory factors in atherogenesis were investigated by real-time quantitative PCR and Western blot analysis. Results Our data demonstrated that ApoE-/- mice fed a high methionine diet generated Hhcy, which subsequently increased the atherosclerotic lesion size significantly, promoted oxidative stress-associated DNA damage and PARP activation, then increased the expression of proinflammatory fac-tors within atherosclerotic plaques. Although PARP inhibition by 3-AB did not markedly inhibit plaque development in ApoE-/- mice with spontaneous hyperlipidemia by feeding a normal diet, it significantly reduced the atherosclerotic lesion size by 40% in Hhcy-induced atherosclerosis without affecting plasma homocysteine levels and lipid contents, effectively suppressed PARP activation, and inhibited nuclear translocation of nuclear factor-(kappa)B (NF-(kappa)B) and subsequent production of inflam-matory factors, such as vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattactant protein-1 (MCP-1). Conclusion Our results suggest that PARP inhibition attenuates atherosclerotic plaque development under hyperhomocysteinemic conditions, through the inhibition of PARP activation, nuclear NF-kappaB translocation and subsequent expression of inflammatory factors.

We investigated the possible protective effect of poly (ADP-ribose) polymerase (PARP) inhibition in preventing endothelial dysfunction induced by hyperhomocysteinemia (Hhcy). Sprague–Dawley rats were divided into Hhcy group, Hhcy + 3-aminobenzamide(3-AB) group, control group and control + 3-AB group. A high-methionine diet was given to induce hyperhomocysteinemia. In Hhcy + 3-AB and control + 3-AB groups, rats were injected intraperitoneally with 3-AB (inhibitor of PARP). After 45 days, ultrastructural changes of aortas were observed by transmission electron microscope. Vascular reactivity of thoracic aortic rings was measured in organ chambers. PARP activity was detected. The levels of plasma total homocysteine, nitrite/nitrate, endothelin (ET)-1 and malondialdehyde were assayed. Rats in Hhcy group developed severe hyperhomocysteinemia and significant loss of endothelial function as measured by both vascular rings and levels of nitrite/nitrate and ET-1. Malondialdehyde levels increased significantly in Hhcy rats compared with control rats. 3-AB improved Ach-induced, NO-mediated vascular relaxation and stabilized the level of nitrite/nitrate and ET-1. Obvious improvement of ultrastructure can be observed in Hhcy + 3-AB group. These results suggest that pharmacological inhibition of PARP prevents the development of endothelial dysfunction in rats with hyperhomocysteinemia which may represent a novel approach to improve vascular dysfunction associated with hyperhomocysteinemia.

Atherosclerosis is a chronic inflammatory disease, which is positively and negatively regulated by T helper (Th) 1 and Th2 lymphocytes, respectively. Recent findings indicate that suppressive oligodeoxynucleotides (ODNs) expressing TTAGGG motifs selectively reduce Th1 cytokine production and have been proven effective at blocking the development of organ-specific autoimmune diseases. In the current research, we hypothesized that suppressive ODNs may alter the development of atherosclerosis. Eight-week-old homozygous ApoE(-/-) male mice were injected with 300 mug ODNs A151 (TTAGGG) or nonspecific ODNs 1612. Atherosclerotic lesion sizes were dramatically reduced by ODNs A151, but not by nonspecific ODNs. MCP-1 and VCAM-1, which are the key inflammatory factors in atherogenesis, were significantly attenuated by the suppressive ODNs A151. In the splenic lymphocytes, FACS analysis showed ODNs A151 reduced the percentage of IFN-gamma-producing Th1 cells and slightly increased the percentage of IL-4-producing Th2 cells, indicating that suppressive ODNs skewed the Th1/Th2 balance toward Th2 inflammation in vivo. Furthermore, ODNs A151 down-regulated the phosphorylation of STAT1 and STAT4 and suppressed up-regulation of T-bet, a signal modulator for Th1, and didn't impact GATA-3 and STAT6, which are associated with a Th2 phenotype. Consistent with this in vivo observation, ELISA analysis demonstrated that ODNs A151 suppressed Th1 cytokines IFN-gamma and TNF-alpha, and augmented Th2 cytokines IL-4 and IL-10 in vitro. This study provides the first experimental evidence that suppressive ODNs inhibit the development of atherosclerosis through inhibition of the STAT1/4 and T-bet pathways, which further modulate the Th1/Th2 balance in vivo.

The purpose of the study was to observe the effect of rapamycin (RAPA) on the differentiation and maturation of rat bone marrow-derived dendritic cells (BMDCs) in vitro. BMDCs from Wistar rats were cultured with granulocyte-macrophage colony-stimulating factor plus interleukin-4 in the presence or absence of RAPA (20 ng/mL), and stimulated with lipopolysaccharide (LPS) for 24 h before cells and supernatants were collected. Surface phenotype of BMDCs was flow-cytometrically detected to determine the expression of maturation markers, MHC class II and CD86. Supernatants were analyzed for the production of IL-12 and IFN-gamma cytokines by using ELISA. BMDCs were co-cultured with T cells from Lewis rats and mixed lymphocyte reaction was assessed by MTT method. The morphology of BMDCs stimulated with LPS remained immature after RAPA pretreatment. RAPA significantly decreased the CD86 expression, impaired the IL-12 and IFN-gamma production of BMDCs stimulated with LPS, and inhibited the proliferation of allogeneic T cells. In conclusion, RAPA can inhibit the maturation of BMDCs stimulated with LPS in terms of the morphology, surface phenotype, cytokine production, and ability of BMDCs to stimulate the proliferation of allogeneic T cells in vitro.

Introduction Statins have been shown to exert anti-inflammatory effects. The aim of this study was to investigate whether rosuvastatin has favorable effect on ventricular remodeling after myocardial infarction (MI), whether this effect is associated with tumor necrosis factor (TNF)-α expression and p38 mitogen-activated protein (MAP) kinase pathway and, furthermore, whether there is close correlation between gene expression of TNF-α and activity of p38 MAP kinase. Methods and Results Adult male Wistar rats with acute MI were randomly divided into 2 groups: (1) rosuvastatin-treated group (MI-R) receiving rosuvastatin 20 mg/kg once daily, and (2) infarcted group (MI) receiving saline, when compared with sham-operated control group. Four weeks later, echocardiography, hemodynamics and Van Gieson staining were applied to evaluate left ventricular remodeling and cardiac function. Myocardial gene expression of TNF-α and activity of p38 MAP kinase were analyzed by real time-polymerase chain reaction and Western blot, respectively. The results demonstrated that increased TNF-α gene expression in noninfarcted areas was accompanied by activation of p38 MAP kinase pathway. Moreover, treatment of rosuvastatin markedly improved ventricular remodeling and cardiac function in rats, which was associated with attenuations in both TNF-α gene expression and p38 MAP kinase activity in myocardium without changes in serum lipid levels. Conclusions Treatment of rosuvastatin was able to improve cardiac remodeling and cardiac function after acute MI, which was associated with attenuations in both expression of TNF-α and activity of p38 MAP kinase in myocardium.

Objective: Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets and have the opposite effects on autoimmunity. Clinical observation has revealed that the Th17/Treg imbalance exists in patients with acute coronary syndrome. We investigated whether the Th17/Treg functional imbalance existed during atherogenesis in ApoE −/− mice. Methods and results: Th17/Treg functions at different levels including cell frequencies, related cytokine secretion and key transcription factors were investigated comparatively between ApoE −/− mice and their age-matched C57BL/6J mice. The results demonstrated that ApoE −/− mice revealed significantly increased secretion of Th17 related cytokines (IL-17 and IL-6) and expression of transcription factor (RORγt) levels and obviously decreased number in Treg cells, secretion of Treg related cytokines (TGF-β 1 ) and expression of transcription factor (Foxp3) levels as compared with age-matched C57BL/6J mice. Th17 related mediators reached their maximum expression values at the early stage (8–16 weeks of age) in ApoE −/− mice, and then followed by continuous depression of their expression levels. Meanwhile, the expression of Treg related mediators was much lower in ApoE −/− mice than in their age-matched wild-type littermates. Conclusions: Th17/Treg functional imbalance exists during atherogenesis in ApoE −/− mice, suggesting a potential role of Th17/Treg imbalance in the formation and progression of atherosclerosis.

Background The T-helper (Th)1/Th2 imbalance has been demonstrated to be involved in chronic heart failure (CHF). We sought to determine whether atorvastatin exhibited any effect on CHF through modulating the Th1/Th2 response. Methods and Results We measured serum concentrations of interleukin (IL)-12, -18, interferon (IFN)-γ, IL-4, and IL-10 from 20 controls and 72 patients with nonischemic CHF by enzyme-linked immunosorbent assay. To investigate the effect of atorvastatin in vivo, CHF patients were either classified into a usual therapy group (n = 35) or usual therapy plus atorvastatin (10 mg/day) group (n = 37). Patient serum levels of IFN-γ and IL-4 were measured at time of admission and 2 weeks after treatment. Peripheral blood mononuclear cells from patients of CHF group were cultured in the presence or absence of atorvastatin (0, 0.4, 1, and 4 μmol/L) in vitro, and IFN-γ and IL-4 levels were detected. Serum levels of IL-12, IL-18, and IFN-γ were significantly higher in the CHF group than in the control group. The levels of IFN-γ and the ratios of IFN-γ:IL-4 were significantly decreased with atorvastatin treatment both in vivo and in vitro, whereas levels of IL-4 did not differ significantly. Conclusions Th1 polarization exists in patients with CHF, and atorvastatin can modulate the Th1/Th2 response through inhibiting Th1 cytokine production.

Oxidative stress and inflammation processes are key components of atherosclerosis, from fatty streak formation to plaque rupture and thrombosis. Evidence has revealed that calcium-channel blockers (CCB) could retard atherogenesis, but the exact mechanisms have not been fully elucidated. The present study was undertaken to investigate the potential effects and molecular mechanisms of the CCB felodipine on the process of atherosclerosis in high-cholesterol-diet (HCD) apolipoprotein E-knockout (ApoE KO) mice. Adult male ApoE KO mice were given a normal diet (ND) or HCD and were randomized to no treatment or felodipine (5 mg / kg per day for 12 weeks). The ApoE KO mice with HCD were associated with a marked increase in plasma lipid levels, atherosclerotic lesion area, and the expressions of NADPH oxidase subunits (p47 and Rac-1), nuclear factor-kappaB (NF-kappaB) in nucleus, phosphor-inhibitors of kappaB (p-IkappaB), tumor necrosis-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and vascular cell-adhesion molecule-1 (VCAM-1). These changes were suppressed in mice that were treated with felodipine (5 mg/kg per day for 12 weeks) concomitant with HCD administration, with no significant change in systolic blood pressure and plasma lipid levels. The results suggest that felodipine can attenuate atherosclerosis, and this effect is partly related to inhibition of oxidative stress and inflammatory signal-transduction pathways, which lead to decreases in the expression of inflammatory cytokines.