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T gene polymorphism in promoter region of CD14 and its significance for plasma lipids levels
Abstracts / Cell Biology International 32 (2008) S1eS67
PRETREATMENT WITH BCG ATTENUATE CARDIAC REMODELING VIA ACTIVATION OF TLR4 Wen Feng Cai, Xiao Wei Zhang, Hui Min Yan, Qing Qing Wang, Liu Yuying, Bing Mu Xing, Han Zhi Liu, Hong Zhen Yang, Zhuo Wei Hu* Institue of Meteria Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Hypertension-induced cardiovascular hypertrophy and fibrosis are critical in the development of heart failure. We wondered if Bacillus Calmette Guerin (BCG), a safe vaccine which has strong immune modulating effect, could prevent cardiac hypertrophy and fibrosis in mice by regulation of immune microenviroment through Toll like receptor 4 (TLR4) and DC-SIGN. Animals received BCG intraperitoneally with or without TLR4 antagonist (msbB) or DC-SIGN inhibitor (mannan) every 3 days for a week before abdominal aortic constriction (AAC). Myocardial hypertrophy and fibrosis were evaluated by echocardiography and pathohistology. Biochemical and immunological changes were investigated by RT-PCR, immunohistochemistry and confocal. Pretreatment of BCG attenuated myocardial hypertrophy and fibrosis, which up-regulated expression of IFN-g and decreased TGF-b, IL-10 in the myocardium. We also found BCG reversed AAC-induced increase in the number of myocardium-infiltrate in M2-macrophages. Moreover, inhibition of TLR4 significantly attenuated the protective effects of BCG, while mannan did not. Our results suggest that BCG can prevent cardiac remodeling induced by pressure overload by modulating immune microenvironment via activation of TLR4.
DAMAGE EFFECTS OF SLEEP DEPRIVATION ON MYOCARDIUM AND ITS ANTIOXYGEN INDEX IN RATS Hui Juan Chai 1, Shu Mei Xu* 1, Hai Xian Yang 2 1 Department of Physiology, Tianjin Medical University, Tianjin, China 2 Center of Electron Microscopy, Tianjin Medical University, Tianjin, China Sleep deprivation is a very common phenomenon in our society now and can cause damaging effects to our body. Using the ‘‘flower pot technique’’ sleep deprivation model, we demonstrated that sleep deprivation could cause damaging effects on myocardium. After sleep deprivation, heart rate increased and ST segments of ECG rose or mixed with T waves showing ischemia of myocardium, P-R interval and Q-T interval prolonged. In addition, cadiocytes lysis or necrosis, subcellular organelles were impaired: the chromosome dissolved gently, the endoplasmic reticulum expanded accompanied with evidence of Ca2+ over loaded. Following morphological changes were observed: structure of the mitochondria blurred; the intercalated disk dissolved; thrombocytes accumulated in microvessels; protein deposited in endotheliocytes interstitium; edema, bleeding and monocytes invasion in the lumen; and lipid peroxidation reaction effects spread widely. In addition to morphological changes, myocardium mitochondrial showed increased malondialdehyde level and increased superoxide dismutase activity followed by a decreased trend as sleep deprivation prolonged. These results suggest that sleep deprivation can induce damage on myocardium and the stress especially oxygen stress caused by sleep deprivation may be the possible mechanism, indicating potential use of antioxidants to treat sleep deprivation.
DISTRIBUTION OF e 159 C/T GENE POLYMORPHISM IN PROMOTER REGION OF CD14 AND ITS SIGNIFICANCE FOR PLASMA LIPIDS LEVELS Fang Chen Department of Clinical Laboratory Science, Second Xiangya Hospital, Central South University, Changsha, China To investigate the distribution of e159 C/T gene polymorphisms in the promoter region of CD14 and its relation to plasma lipid levels in normal Chinese Han population in Hunan, genotypes of CD14 were typed in 118 normal men by PCR - RFLP and their plasma lipid levels were assessed. The - 159C/T gene polymorphism was present in normal Han population of Hunan, and the frequencies of CC, CT and TT were 19.5 %, 51.7 %, and 28.8 %,
S13
respectively. The TT genotype carriers had lower plasma low - density lipoprotein cholesterol (LDL - C) level than that of the CT and TT genotype carriers (P < 0.001, P < 0.05). No association was found between the genotypes and plasma levels of total cholesterol, triglyceride, high -density lipoprotien, apolipoprotein A1, apolipoprotein B100 and body mass index. TT genotype significantly influenced the plasma levels of LDL - C in the normal Chinese Han population.
RECONSTITUTION OF CORONARY VASCULATURE IN ISCHEMIC HEARTS Hao Chen 1,2, Lei Cheng 2, Jie Ting Zhang 1, Ming Li 1,2, Hsiao Chang Chan 1,2 1 Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong 2 Joint Laboratory For Regenerative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong In the remodeling process of post myocardial infarction, limited neoangiogenesis to the infarct-bed capillary is insufficient to support the greater demands of the hypertrophied but viable myocardium, which results in further ischemic injury to the viable cardiomyocytes at risk. Here we reported the rapid angiogenic effect induced by the extracts from Dagencao (angio-T) to form functional vasculature and the promoted survival potential of the viable cardiomyocytes at risk after myocardial infarction. Our results demonstrated dual effects of angio-T on up-regulating expression of angiogenic factors and protection of the cardiomyocytes against further ischemic injury. Echocardiograph studies demonstrated significant functional improvement of the infracted hearts by 2 days after infarction and angio-T treatment. These therapeutic properties of angio-T to induce early reconstitution of a blood supply network, and improve heart function post infarction appear entirely novel and may provide a new dimension for therapeutic angiogenesis medicine for the treatment of ischemic heart diseases.
COATING PREPARATION AND DRUG DELAYED RELEASE IN VITRO AND IN VIVO OF DEXAMETHASONE-ELUTING INTRAVASCULAR STENTS Yong Peng Chen 1,2, Gui Xue Wang* 2, Xian Chun Jin 1, Lai Long Luo 2, Gang Zhang 1, Laichun Lu 1 1 Xinqiao Hospital, Third Military Medical University, Chongqing, China 2 Bioengineering College and ‘‘111 Project’’ Laboratory of Biomechanics and Tissue Repair, Chongqing University, Chongqing, China To observe the effect of drug delayed release in vitro and in vivo in dexamethasone-eluting intravascular stent, we prepared stents by dip coating, and then high performance liquid chromatography (HPLC) was used to detect the drug loading. The weight of bare stents and drug eluting stents were determined. NETZSCH thermal analyser was used to analyze dexamethasone. The drug slow-release rate in vitro was detected with parallel plate flow chamber perfusion system, and then the dexamethasone-eluting intravascular stents were implanted into rabbit abdominal aorta to detect drug slow-release character in vivo. The blood flow velocity of rabbit abdominal aorta was detected by ultrasonic inspection. The results showed the drug loading of stents prepared by dip coating for four days was 93.15 7.83mg. The weight of drug load was about 13.70 0.84 % in the coating. Differential scanning calorimetry (DSC) indicated that the melting point was 259.3 C, which was coincided with 254e264 C in the pharmacopoeia of the People’s Republic of China. The thermogravimetry (TG) curve indicated the rate of loss in weight of dexamethasone was 76.67% from 250 C to 400 C. DSC and TG curve hinted the course of evaporation and sublimation of dexamethasone on the temperature. Drugs were released slowly and the release rate reached 84 % at 15d. The maximum blood flow velocity of abdominal aorta was 27.03 3.25 cm/s, while the minimum velocity was 12.13 2.20 cm/s. The drug concentration detected after implantation 2 hours was 4.59mg/g in vessel wall and 1.91 mg/g in liver, respectively. The drug concentration detected after implantation 10 days was
PRETREATMENT WITH BCG ATTENUATE CARDIAC REMODELING VIA ACTIVATION OF TLR4 Wen Feng Cai, Xiao Wei Zhang, Hui Min Yan, Qing Qing Wang, Liu Yuying, Bing Mu Xing, Han Zhi Liu, Hong Zhen Yang, Zhuo Wei Hu* Institue of Meteria Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Hypertension-induced cardiovascular hypertrophy and fibrosis are critical in the development of heart failure. We wondered if Bacillus Calmette Guerin (BCG), a safe vaccine which has strong immune modulating effect, could prevent cardiac hypertrophy and fibrosis in mice by regulation of immune microenviroment through Toll like receptor 4 (TLR4) and DC-SIGN. Animals received BCG intraperitoneally with or without TLR4 antagonist (msbB) or DC-SIGN inhibitor (mannan) every 3 days for a week before abdominal aortic constriction (AAC). Myocardial hypertrophy and fibrosis were evaluated by echocardiography and pathohistology. Biochemical and immunological changes were investigated by RT-PCR, immunohistochemistry and confocal. Pretreatment of BCG attenuated myocardial hypertrophy and fibrosis, which up-regulated expression of IFN-g and decreased TGF-b, IL-10 in the myocardium. We also found BCG reversed AAC-induced increase in the number of myocardium-infiltrate in M2-macrophages. Moreover, inhibition of TLR4 significantly attenuated the protective effects of BCG, while mannan did not. Our results suggest that BCG can prevent cardiac remodeling induced by pressure overload by modulating immune microenvironment via activation of TLR4.
DAMAGE EFFECTS OF SLEEP DEPRIVATION ON MYOCARDIUM AND ITS ANTIOXYGEN INDEX IN RATS Hui Juan Chai 1, Shu Mei Xu* 1, Hai Xian Yang 2 1 Department of Physiology, Tianjin Medical University, Tianjin, China 2 Center of Electron Microscopy, Tianjin Medical University, Tianjin, China Sleep deprivation is a very common phenomenon in our society now and can cause damaging effects to our body. Using the ‘‘flower pot technique’’ sleep deprivation model, we demonstrated that sleep deprivation could cause damaging effects on myocardium. After sleep deprivation, heart rate increased and ST segments of ECG rose or mixed with T waves showing ischemia of myocardium, P-R interval and Q-T interval prolonged. In addition, cadiocytes lysis or necrosis, subcellular organelles were impaired: the chromosome dissolved gently, the endoplasmic reticulum expanded accompanied with evidence of Ca2+ over loaded. Following morphological changes were observed: structure of the mitochondria blurred; the intercalated disk dissolved; thrombocytes accumulated in microvessels; protein deposited in endotheliocytes interstitium; edema, bleeding and monocytes invasion in the lumen; and lipid peroxidation reaction effects spread widely. In addition to morphological changes, myocardium mitochondrial showed increased malondialdehyde level and increased superoxide dismutase activity followed by a decreased trend as sleep deprivation prolonged. These results suggest that sleep deprivation can induce damage on myocardium and the stress especially oxygen stress caused by sleep deprivation may be the possible mechanism, indicating potential use of antioxidants to treat sleep deprivation.
DISTRIBUTION OF e 159 C/T GENE POLYMORPHISM IN PROMOTER REGION OF CD14 AND ITS SIGNIFICANCE FOR PLASMA LIPIDS LEVELS Fang Chen Department of Clinical Laboratory Science, Second Xiangya Hospital, Central South University, Changsha, China To investigate the distribution of e159 C/T gene polymorphisms in the promoter region of CD14 and its relation to plasma lipid levels in normal Chinese Han population in Hunan, genotypes of CD14 were typed in 118 normal men by PCR - RFLP and their plasma lipid levels were assessed. The - 159C/T gene polymorphism was present in normal Han population of Hunan, and the frequencies of CC, CT and TT were 19.5 %, 51.7 %, and 28.8 %,
S13
respectively. The TT genotype carriers had lower plasma low - density lipoprotein cholesterol (LDL - C) level than that of the CT and TT genotype carriers (P < 0.001, P < 0.05). No association was found between the genotypes and plasma levels of total cholesterol, triglyceride, high -density lipoprotien, apolipoprotein A1, apolipoprotein B100 and body mass index. TT genotype significantly influenced the plasma levels of LDL - C in the normal Chinese Han population.
RECONSTITUTION OF CORONARY VASCULATURE IN ISCHEMIC HEARTS Hao Chen 1,2, Lei Cheng 2, Jie Ting Zhang 1, Ming Li 1,2, Hsiao Chang Chan 1,2 1 Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong 2 Joint Laboratory For Regenerative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong In the remodeling process of post myocardial infarction, limited neoangiogenesis to the infarct-bed capillary is insufficient to support the greater demands of the hypertrophied but viable myocardium, which results in further ischemic injury to the viable cardiomyocytes at risk. Here we reported the rapid angiogenic effect induced by the extracts from Dagencao (angio-T) to form functional vasculature and the promoted survival potential of the viable cardiomyocytes at risk after myocardial infarction. Our results demonstrated dual effects of angio-T on up-regulating expression of angiogenic factors and protection of the cardiomyocytes against further ischemic injury. Echocardiograph studies demonstrated significant functional improvement of the infracted hearts by 2 days after infarction and angio-T treatment. These therapeutic properties of angio-T to induce early reconstitution of a blood supply network, and improve heart function post infarction appear entirely novel and may provide a new dimension for therapeutic angiogenesis medicine for the treatment of ischemic heart diseases.
COATING PREPARATION AND DRUG DELAYED RELEASE IN VITRO AND IN VIVO OF DEXAMETHASONE-ELUTING INTRAVASCULAR STENTS Yong Peng Chen 1,2, Gui Xue Wang* 2, Xian Chun Jin 1, Lai Long Luo 2, Gang Zhang 1, Laichun Lu 1 1 Xinqiao Hospital, Third Military Medical University, Chongqing, China 2 Bioengineering College and ‘‘111 Project’’ Laboratory of Biomechanics and Tissue Repair, Chongqing University, Chongqing, China To observe the effect of drug delayed release in vitro and in vivo in dexamethasone-eluting intravascular stent, we prepared stents by dip coating, and then high performance liquid chromatography (HPLC) was used to detect the drug loading. The weight of bare stents and drug eluting stents were determined. NETZSCH thermal analyser was used to analyze dexamethasone. The drug slow-release rate in vitro was detected with parallel plate flow chamber perfusion system, and then the dexamethasone-eluting intravascular stents were implanted into rabbit abdominal aorta to detect drug slow-release character in vivo. The blood flow velocity of rabbit abdominal aorta was detected by ultrasonic inspection. The results showed the drug loading of stents prepared by dip coating for four days was 93.15 7.83mg. The weight of drug load was about 13.70 0.84 % in the coating. Differential scanning calorimetry (DSC) indicated that the melting point was 259.3 C, which was coincided with 254e264 C in the pharmacopoeia of the People’s Republic of China. The thermogravimetry (TG) curve indicated the rate of loss in weight of dexamethasone was 76.67% from 250 C to 400 C. DSC and TG curve hinted the course of evaporation and sublimation of dexamethasone on the temperature. Drugs were released slowly and the release rate reached 84 % at 15d. The maximum blood flow velocity of abdominal aorta was 27.03 3.25 cm/s, while the minimum velocity was 12.13 2.20 cm/s. The drug concentration detected after implantation 2 hours was 4.59mg/g in vessel wall and 1.91 mg/g in liver, respectively. The drug concentration detected after implantation 10 days was