interleukin-8 and Hyperlipidemias

Diabetes mellitus is a systemic disease with several major complications affecting both the quality and length of life. One of these complications is periodontal disease (periodontitis). Periodontitis is much more than a localized oral infection. Recent data indicate that periodontitis may cause changes in systemic physiology. The interrelationships between periodontitis and diabetes provide an example of systemic disease predisposing to oral infection, and once that infection is established, the oral infection exacerbates systemic disease. In this case, it may also be possible for the oral infection to predispose to systemic disease. In order to understand the cellular/molecular mechanisms responsible for such a cyclical association, one must identify common physiological changes associated with diabetes and periodontitis that produce a synergy when the conditions coexist. A potential mechanistic link involves the broad axis of inflammation, specifically immune cell phenotype, serum lipid levels, and tissue homeostasis. Diabetes-induced changes in immune cell function produce an inflammatory immune cell phenotype (upregulation of proinflammatory cytokines from monocytes/polymorphonuclear leukocytes and downregulation of growth factors from macrophages). This predisposes to chronic inflammation, progressive tissue breakdown, and diminished tissue repair capacity. Periodontal tissues frequently manifest these changes because they are constantly wounded by substances emanating from bacterial biofilms. Diabetic patients are prone to elevated low density lipoprotein cholesterol and triglycerides (LDL/TRG) even when blood glucose levels are well controlled. This is significant, as recent studies demonstrate that hyperlipidemia may be one of the factors associated with diabetes-induced immune cell alterations. Recent human studies have established a relationship between high serum lipid levels and periodontitis. Some evidence now suggests that periodontitis itself may lead to elevated LDL/TRG. Periodontitis-induced bacteremia/endotoxemia has been shown to cause elevations of serum proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), which have been demonstrated to produce alterations in lipid metabolism leading to hyperlipidemia. Within this context, periodontitis may contribute to elevated proinflammatory cytokines/serum lipids and potentially to systemic disease arising from chronic hyperlipidemia and/o

Topics: Bacteremia; Bacterial Infections; Biofilms; Blood Glucose; Cholesterol, LDL; Diabetes Complications; Diabetes Mellitus; Disease Susceptibility; Down-Regulation; Endotoxemia; Growth Substances; Homeostasis; Humans; Hyperlipidemias; Inflammation; Inflammation Mediators; Insulin Resistance; Interleukin-8; Islets of Langerhans; Periodontitis; Phenotype; Risk Factors; Triglycerides; Tumor Necrosis Factor-alpha; Up-Regulation; Wound Healing

We investigated whether pro-inflammatory aspects of the postprandial phase can be modulated by rosuvastatin in premature coronary artery disease (CAD) patients. Herefore standardized 8 h oral fat loading tests were performed off-treatment and after rosuvastatin 40 mg/d in 20 male CAD patients (50 +/- 4 years). The expression of leukocyte activation markers CD11a, CD11b, CD62L and CD66b was studied using flowcytometry. Migration of isolated neutrophils towards chemoattractants was determined in a fluorescence-based assay. Rosuvastatin did not affect baseline leukocyte counts nor the postprandial neutrophil increment (maximum mean increase +10% pre- and +14% post-treatment, P < 0.01 for each). Rosuvastatin reduced baseline platelets (from 266 +/- 78 to 225 +/- 74 x 10(9) cells/L, P < 0.001) and blunted the postprandial platelet count change (maximum mean increase +6%, P = 0.01, and 0%, respectively). The baseline expression of CD11a, CD11b and CD62L increased on most types of leukocytes by rosuvastatin, whereas the postprandial responses were unaffected. Pretreatment, postprandial neutrophil migration increased dose-dependently, but there were no postprandial changes after rosuvastatin. The latter effect was unrelated to changes in lipoprotein concentrations. In conclusion, in CAD patients postprandial pro-inflammatory and pro-coagulant changes can be modified by rosuvastatin. These apparently lipid-lowering independent effects may render protection against atherosclerosis.

Topics: Adult; Antigens, CD; CD11a Antigen; CD11b Antigen; Cell Adhesion Molecules; Chemotaxis, Leukocyte; Coronary Artery Disease; Dietary Fats; Erythrocyte Count; Fluorobenzenes; GPI-Linked Proteins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Interleukin-8; L-Selectin; Leukocytes; Male; Middle Aged; Neutrophils; Oxidative Stress; Platelet Count; Postprandial Period; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Vascular Cell Adhesion Molecule-1

The molecular regulation for the transition from stable to vulnerable plaque remains to be elucidated. Heme oxygenase 1 (HO-1) and its metabolites have been implicated in the cytoprotective defense against oxidative injury in atherogenesis. In this study, we sought to assess the role of HO-1 in the progression toward plaque instability in carotid artery disease in patients and in a murine model of vulnerable plaque development.. Atherectomy biopsy from 112 patients with clinical carotid artery disease was collected and stratified according to characteristics of plaque vulnerability. HO-1 expression correlated closely with features of vulnerable human atheromatous plaque (P<0.005), including macrophage and lipid accumulation, and was inversely correlated with intraplaque vascular smooth muscle cells and collagen deposition. HO-1 expression levels correlated with the plaque destabilizing factors matrix metalloproteinase-9, interleukin-8, and interleukin-6. Likewise, in a vulnerable plaque model using apolipoprotein E(-/-) mice, HO-1 expression was upregulated in vulnerable versus stable lesions. HO-1 induction by cobalt protoporphyrin impeded lesion progression into vulnerable plaques, indicated by a reduction in necrotic core size and intraplaque lipid accumulation, whereas cap thickness and vascular smooth muscle cells were increased. In contrast, inhibition of HO-1 by zinc protoporphyrin augmented plaque vulnerability. Plaque stabilizing was prominent after adenoviral transduction of HO-1 compared with sham virus-treated animals, providing proof that the observed effects on plaque vulnerability were HO-1 specific.. Here we demonstrate in a well-defined patient group and a murine vulnerable plaque model that HO-1 induction reverses plaque progression from a vulnerable plaque to a more stable phenotype as part of a compensatory atheroprotective response.

Topics: Aged; Animals; Apolipoproteins E; Carotid Artery Diseases; Collagen; Disease Models, Animal; Disease Progression; Female; Heme Oxygenase-1; Humans; Hyperlipidemias; Interleukin-6; Interleukin-8; Macrophages; Male; Matrix Metalloproteinase 9; Mice; Mice, Mutant Strains; Middle Aged; Muscle, Smooth, Vascular; Thrombosis; Transfection

Interleukin-8 is CXC chemokine that is initially discovered using chemotaxis and the activation of neutrophils and induces the migration and proliferation of smooth muscle cells. Interleukin-8 is a potent angiogenic factor that may play a role in atherosclerosis. To establish the temporal correlation between IL-8 expression and plaque development, we examined the expression during atherosclerosis of hyperlipemia rabbits using immunohistochemistry, ELISA, in situ hybridization. By location of immunohistochemistry, the expression of IL-8 protein increased obviously in intima of hyperlipemia rabbits at 8 and 12 week. Quantitative analysis of the expression of IL-8 Immunohistochemistry indicated that positive area of AS model was 4.48 times and 8.76 times that of control group at 8 and 12 week. The valuation of IOD of AS model was 4.16 times and 4.36 times that of control group at 8 and 12 week. By specific ELISA, the ratio of the IL-8 protein to total protein of AS model was 1.84 times and 2.06 times that of control group at 8 and 12 week. By location of in situ hybridization, positive location was strong in intima of hyperlipemia rabbits at 8 week. We observed the dynamic alteration of interleukin-8 protein and gene expression in atherosclerotic lesions of hyperlipemia rabbits with establishing model. Interleukin-8 protein and gene expression was up-regulation in the development of fatty streaks in hyperlipemia rabbit.

Topics: Animals; Aorta; Atherosclerosis; Hyperlipidemias; Interleukin-8; Male; Rabbits; RNA, Messenger