P12 prevention of activated macrophage-induced adhesion molecules by chlorella extract in endothelial sevc cells

Atherosclerosis Supplements 11, no. 2 (2010) 17–108 P10 TARGETED STERICALLY STABILIZED LIPOSOMES FOR
Endothelial cells (SEVC cell line) were treated with conditioned culture media DIAGNOSTIC IMAGING OF ATHEROSCLEROTIC PLAQUES
(normal culture media contains 50% of LPS-activated macrophage culture R. Prassl1, G. Almer2, M. Saba-Lepek1, D. Frascione1, J. Kellner3, A. Gries3, media, in which there contained TNF-a, IL-1, and IL-6) with or without C. Diwoky4, R. Stollberger4, H. Mangge2. 1Institute of Biophysics and high (0.5 mg/ml) or low (0.125 mg/ml) dose of PPLEC extracts. Indomethacin Nanosystems Research, Austrian Academy of Sciences, 2 Clinical Institute for (0.25 mM) was used as a positive control. Production of VCAM-1, ICAM-1 and Medical and Chemical Diagnosis, 3 Institute of Physiology, Medical University E-selectin was measured by ELISA assay kits.
Graz, 4Institute of Medical Engineering, University of Technology Graz, Graz, Production of ICAM, VCAM or E-selectin was all increased by additional RAW culture media in SEVC cells. The induction of E-selectin and ICAM was We have designed polyethylene glycol (PEG-) coated (sterically stabilized) significantly prevented by both high and low doses of PPLEC or indomethacin liposomes to carry high payloads of imaging reagents such as paramagnetic treatment. However, the prevention of VCAM production was only seen in high compounds (e.g. fluorescent dyes) to cells with the goal to improve non-invasive PPLEC not only possess anti-inflammatory effect (previous study) but also molecular imaging modalities by specific targeting. To target atherosclerotic prevents pro-inflammatory cytokines-induced adhesion molecule production in plaques we have covalently coupled selected biomarkers to the distal ends endothelia. These data indicate that PPLEC can be a potential material to of the PEG-chains, which are located at the surface of the liposomes. These develop in preventing chronic inflammatory-related diseases.
functionalized liposome constructs were characterized by photon correlation P13 CILOSTAZOL AMELIORATES METABOLIC ABNORMALITIES IN
spectroscopy, modified native gel electrophoresis and Western Blot. As A DB/DB MOUSE MODEL OF TYPE 2 DIABETES VIA ACTIVATION
targeting sequences we have chosen interleukin-10 (IL-10), the globular OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORg
domain of adiponectin (gAcrp30) and anti-LOX-1 mAB. These biomarkers TRANSCRIPTION
bind to atherosclerotic aortas of ApoE-deficient mice as shown by ex vivoimaging using confocal laser-scanning microscopy (CLSM). For the ligand- S.Y. Park, K.W. Hong, W.S. Lee, C.D. Kim. Medical Research Center for conjugated liposomes we found a pronounced signal enhancement ex vivo, Ischemic Tissue Regeneration; Department of Pharmacology, Pusan National whereas no signal was detected in less injured aortic surfaces or in arteries University, Gyeongnam, Republic of Korea of WT-mice. With IL-10-targeted liposomes we already observed a strong This study evaluated the in vivo efficacy of cilostazol to protect a db/db in vivo staining signal with CLSM. Now, Gd-DTPA-lipid and ultra small mouse model of Type 2 diabetes against altered metabolic abnormalities ironoxide nanoparticle (USPIOs) containing targeted liposomes are established and pro-inflammatory markers via activation of PPARg transcription. Eight- to improve image sensitivity for in vivo magnetic resonance imaging (MRI).
week old db/db mice were treated with cilostazol or rosiglitazone for 12 days.
A contrast enhancement in terms of T1-relaxivity or in hypotense T2-signals Cilostazol significantly decreased plasma glucose and triglyceride levels, as could be achieved for paramagnetic or magneto-liposomes, respectively. In did rosiglitazone, a PPARg agonist. Elevated plasma insulin and resistin levels conclusion, the combinatory use of specific anti-inflammatory biomarkers as were significantly decreased by cilostazol, and decreased adiponectin mRNA targeting sequences and multiple or high payloads of contrast agents within expression was elevated along with increased plasma adiponectin. Cilostazol one liposome particle opens the opportunity for early recognition, differentiation significantly increased both adipocyte fatty acid binding protein (aP2) and fatty and visualization of unstable vulnerable atherosclerotic plaques by imaging.
acid transport protein (FATP-1) mRNA expressions with increased glucosetransport 4 in the adipose tissue.
P11 WHHLMI RABBIT IS AN ANIMAL MODEL FOR ANGINA AND/OR
Cilostazol and rosiglitazone significantly suppressed pro-inflammatory markers CORONARY SPASMS
(superoxide, TNF-a and vascular cell adhesion molecule-1) in the carotid artery T. Kobayashi1, T. Ito1, S. Yamada1, N. Hirayama1, K. Hirata2, T. Ishida2, of db/db mice. In in vitro study with 3T3-L1 fibroblasts, cilostazol significantly M. Shiomi1. 1Institute for Experimental Animals, 2 Division of Cardiovascular increased PPARg transcription activity, as did rosiglitazone. The transcription Medicine, Kobe University Graduate School of Medicine, Kobe, Japan activity stimulated by cilostazol was attenuated by KT5720, a cAMP-dependentprotein kinase inhibitor, and GW9662, an antagonist of PPARg activity, indicative Purpose: Coronary spasms are one of the important causes of myocardial
of implication of PI3-k/Akt signal pathway. These results suggest that cilostazol ischemia. However, the mechanisms of coronary spasms and the highly may improve insulin sensitivity along with anti-inflammatory effects in Type 2 susceptible regions are still unknown because of the lack of suitable animal diabetic patients via activation of both cAMP-dependent protein kinase and models for the disease. Therefore, we are trying to develop an animal model for coronary spasms and/or angina.
Methods: Coronary atherosclerosis and myocardial infarction-prone Watanabe
P14 PREVENTION OF DOCA/SALT HYPERTENSION-INDUCED RAT
RENAL INJURY BY ANTIOXIDANT THERAPY
Under anesthesia with intravenous injection of ketamine plus midazolam,WHHLMI rabbits were administered intravenously with serotonin, ergonovine, M. Kadkhodaee1, B. Seifi1, S.M. Karimian1, M. Zahmatkesh1, E. Bakhshi2.
1 dobutamine, norepinephrin, or angiotensin-II. ECG and blood pressure at the Physiology, 2 Biostatistics, Tehran Medical Sciences University, Tehran, Iran femoral artery were recorded during the experiment. After examination of ECG, Introduction: Hypertension is a major cardiovascular risk factor and a
the coronary atherosclerosis was examined histopathologically.
contributor to End Stage Renal Disease. This study examined whether the Results: The blood pressure was raised by more than 50 mmHg with
antioxidant therapy with vitamin-E or C, could modify renal damage and high intravenous injection of each drug. ECG documented depression of the blood pressure in DOCA-salt induced hypertension.
ST segment, reduction of R-wave amplitude, or T-inversion. Ventricular Methods: One week after uninephrectomy, rats in the DOCA-salt group treated
arrhythmia was also observed after bolus injection of serotonin or ergonovine 5 times a week with DOCA suspended in oil, which were administered in combination with the perfusion of dobutamine, norepinephrin or angiotensin subcutaneously for 4 weeks (25 mg/kg). 1% NaCl + 0.2% KCl were added II. These ECG changes were correlated with the degree of coronary to their water for drinking. Sham rats were received oil, 5 times a week, subcutaneously. In the two other groups vitamin-E (200 mg/kg/day/gavage) or Conclusions: WHHLMI rabbits will be an useful animal model for angina
vitamin C (200 mg/kg/day/gavage) were co-administered with DOCA-salt for 4 in which coronary spasm and subsequent myocardial ischemia can be weeks. Systolic blood pressure (SBP) was measured by the tail-cuff method.
Levels of renal antioxidants, renal damage indices and histological changeswere studied in all groups.
P12 PREVENTION OF ACTIVATED MACROPHAGE-INDUCED ADHESION
Results: DOCA-salt treated rats exhibited marked increase in blood pressure
MOLECULES BY CHLORELLA EXTRACT IN ENDOTHELIAL
compared to that in sham group (183.57±6.24 vs 109.28±2.97 mmHg).
SEVC CELLS
Levels of urinary N-acetyl glucoaminidase) NAG and protein excretion were M.-F. Shih1, J.-Y. Cherng2. 1Pharmacy, Chia-Nan University of Pharmacy significantly increased. Decreased renal reduced glutathione (GSH) contents & Science, Tainan, 2 Biochemistry & Chemistry, National Chung Cheng and ferric reducing ability of plasma (FRAP) were demonstrated in DOCA-salt University, Chia-Yi, Taiwan R.O.C. treatment as well as histological changes. Treatment with vitamin C or vitamin-Efor 4 weeks preserved the renal antioxidant levels and prevented renal damage The inflammatory response in large vessels involves the up-regulation of and elevation of blood pressure in the DOCA-salt treatment.
vascular adhesion molecules such as vascular cell adhesion molecule Conclusions: Antioxidant therapy decreased renal damage in DOCA-salt
(VCAM)-1, intercellular adhesion molecule (ICAM-1), and E-selectin. Inflamma- treated rats. These data suggests a role for oxidative stress in the development tory cytokines such as TNF-a, IL-1, or IL-6 are thought to play important roles in of nephropathy in DOCA-salt hypertension.
the development of atherosclerosis. Chlorella has been shown to lower high fatdiet-induced atherosclerosis. In addition, we have previously shown that partialpurified lipophilic chlorella extract (PPLEC) possess strong anti-inflammatoryeffect. The aim of this study is to investigate the possible preventing role ofPPLEC on pro-inflammatory cytokine-induced expression of vascular adhesionmolecules.

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