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Porphyromonas gingivalis,a periodontal pathogen,impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion

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International Journal of Oral Science 2023年第4期15卷 626-639页

作者： Yuka Shiheido-Watanabe Yasuhiro Maejima Shun Nakagama Qintao Fan Natsuko Tamura Tetsuo Sasano Department of Cardiovascular Medicine Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan

While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes(NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.

关键词： inhibiting myocardium periodontal

In vivo mechanical study of helical cardiac pacing electrode interacting with canine myocardium

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Acta Mechanica Sinica 2007年第3期23卷 275-280页

作者： Xiangming Zhang Nianke Ma Hualin Fan Guodong Niu Wei Yang Department of Engineering Mechanics Tsinghua University Beijing 100084 China Fuwai Angiocardiopathy Hospital Beijing 100037 China Zhejiang University Hangzhou 310027 China

Cardiac pacing is a medical device to help human to overcome arrhythmia and to recover the regular beats of heart. A helical configuration of electrode tip is a new type of cardiac pacing lead distal tip. The helical electrode attaches itself to the desired site of heart by screwing its helical tip into the myocardium. In vivo experiments on anesthetized dogs were carried out to measure the acute interactions between helical electrode and myocardium during screw-in and pull-out processes. These data would be helpful for electrode tip design and electrode/myocardium adherence safety evaluation. They also provide reliability data for clinical site choice of human heart to implant and to fix the pacing lead. A special design of the helical tip using strain gauges is instrumented for the measurement of the screw-in and pull-out forces. We obtained the data of screw-in torques and pull-out forces for five different types of helical electrodes at nine designed sites on ten canine hearts. The results indicate that the screw-in torques increased steplike while the torque-time curves presente saw-tooth fashion. The maximum torque has a range of 0.3-1.9 Nmm. Obvious differences are observed for different types of helical tips and for different test sites. Large pull-out forces are frequently obtained at epicardium of left ventricle and right ventricle lateral wall, and the forces obtained at right ventricle apex and outflow tract of right ventricle are normally small. The differences in pull-out forces are dictated by the geometrical configuration of helix and regional structures of heart muscle.

关键词： Cardiac pacing Helical electrode Acute Interactions myocardium

Efficient Gene Delivery to myocardium with Ultrasound Targeted Microbubble Destruction and Polyethylenimine

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2008年第5期28卷 613-617页

作者：陈智毅谢明星王新房吕清丁尚伟 Department of Ultrasonography Union Hospital Tongji Medical College Huazhong University of Science and Technology Hubei Province Key Laboratory of Molecular Imaging

The aim of present study was to evaluate the feasibility and efficiency of enhanced green fluorescent protein （EGFP） gene delivery to myocardium in vivo by ultrasound targeted microbubble destruction （UTMD） and polyethylenimine （PEI）. SonoVue/DNA and PEI/DNA/SonoVue complexes were prepared. Gel electrophoresis analysis was performed to determine the structural integrity of plasmid DNA or PEI/DNA after UTMD. Solutions of plasmid DNA, SonoVue/DNA, PEI/DNA complexes or PEI/DNA/SonoVue complexes were respectively transduced into BALB/c mice hearts by means of transthoracic ultrasound irradiation. Mice undergoing PBS injection, plasmid injection or PEI/DNA complexes injection without ultrasound irradiation served as controls. Gene expression in myocardium was detected 4 days after treatment. Cryosections and histological examinations were conducted. Electrophoresis gel assay showed no damage to DNA or PEI/DNA complexes after UTMD. When the heart was not exposed to ultrasound, the expression of EGFP was observed in the subendocardial myocardium obviously. The strongest expression was detected in the anterior wall of the left ventricle when the heart was exposed to ultrasound alone. Injection of PEI/DNA complexes and UTMD resulted in the highest transfection efficiency and the distributional difference of EGFP was not obvious. No tissue damage was seen histologically. In conclusion, a combination of UTMD and PEI was highly effective in transfecting mice hearts without causing any apparently adverse effect. It provides an alternative to current clinical gene therapy and opens a new concept of non-viral gene delivery for the treatment of cardiac disease.

关键词： ultrasound polyethylenimine gene delivery microbubble myocardium

Parthenolide attenuates LPS-induced activation of NF-κB in a time-dependent manner in rat myocardium

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The Journal of Biomedical Research 2012年第1期26卷 37-43页

作者： Hong Xie Chen Wang Xuemei Wu Xia Liu Shigang Qiao Chunfeng Liu Hong Liu Department of Anesthesiology the Second Affiliated Hospital of Sooehow University Suzhou 215004 China Institute of Neuroseienee Sooehow University Suzhou 215004 China Department of Anesthesiology and Pain Medicine University of California Davis Davis CA 95616 USA

Parthenolide （PTN）, a selective nuclear factor kappa B （NF-κB） inhibitor, has been used extensively to inhibit NF-κB activation. The duration of the inhibitory effect of PTN on NF-kB in vivo remains unclear. This study was to determine whether a lipopolysaccharide （LPS） challenge 6, 12 and 24 h after the administration of PTN could activate NF-κB. Rats were devided into five groups. The rats in the PTN, PTN＋LPS and DMSO groups were injected intraperitoneally with PTN or DMSO. After 6, 12 or 24 h, LPS was administered in LPS and PTN＋LPS groups. The expressions of NF-κB p50, IκBα and p-IκBα were inhibited in both PTN and PTN＋LPS group at end of 6 and 12 h and no effects at 24 h. In summary, myocardial NF-κB expression occurs 1 h after the administration of LPS. PTN blocks this effect given at 6 h and no inhibitory effect 24 h after administration in vivo.

关键词： parthenolide nuclear-factor-κB lipopolysaccharide myocardium

Predictive value of the proportion of hibernating myocardium in total perfusion defect on reverse remodeling in patients with HFrEF undergoing coronary artery bypass graft

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中国医学文摘:内科学分册(英文版) 2023年第2期40卷 93-94页

作者：鲁瑶 Dept Nucl Med Molecular Imaging LabBeijing Anzhen HospCapital Med UnivBeijing 100029

Objective To evaluate the predictive value of the proportion of hibernating myocardium(HM)in total perfusion defect(TPD)on reverse left ventricle remodeling(RR)after coronary artery bypass graft(CABG)in patients with heart failure with reduced ejection fraction(HFrEF)by ^(99m)Tc-methoxyisobutylisonitrile(MIBI)single photon emission computed tomography(SPECT)myocardial perfusion imaging(MPI)combined with ^(18)F-flurodeoxyglucose(FDG)gated myocardial imaging positron emission computed tomography(PET).

关键词： bypass myocardium perfusion

Blockade of L-type calcium channel in myocardium and calcium-induced contractions of vascular smooth muscle by CPU 86017

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Acta Pharmacologica Sinica 2004年第4期 18-25页

作者： De-zai DAI2, Hui-juan HU3, JingZHAO, Xue-mei HAO4, Dong-mei YANG4, Pei-ai ZHOU4,Cai-hong WU4 Research Division of Pharmacology, China Pharmaceutical University, Nanjing, 210009 4National Laboratoryof Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871, China

AIM: To assess the blockade by CPU 86017 on the L-type calcium channels in the myocardium and on the Ca2+- related contractions of vascular smooth muscle. METHODS: The whole-cell patch-clamp was applied to investi- gate the blocking effect of CPU 86017 on the L-type calcium current in isolated guinea pig myocytes and contrac- tions by KCl or phenylephrine (Phe) of the isolated rat tail arteries were measured. RESULTS: Suppression of the L-type current of the isolated myocytes by CPU 86017 was moderate, in time- and concentration-dependent man- ner and with no influence on the activation and inactivation curves. The IC50was 11.5 μmol/L. Suppressive effect of CPU 86017 on vaso-contractions induced by KCl 100 mmol/L, phenylephrine 1 μmol/Lin KH solution (phase 1), Ca2+ free KH solution ( phase 2) , and by addition of CaCl2 into Ca2+-free KH solution (phase 3) were observed. The IC50 to suppress vaso-contractions by calcium entry via the receptor operated channel (ROC) and voltage-depen- dent channel (VDC) was 0.324 μmol/L and 16.3 μmol/L, respectively. The relative potency of CPU 86017 to suppress vascular tone by Ca2+ entry through ROC and VDC is 1/187 of prazosin and 1/37 of verapamil, respectively. CONCLUSION: The blocking effects of CPU 86017 on the L-type calcium channel of myocardium and vessel are moderate and non-selective. CPU 86017 is approximately 50 times more potent in inhibiting ROC than VDC.

关键词： chlorobenzyltetrahydroberine myocardium vascular smooth muscle patch-clamp techniques berberine calcium

Protective Effects of Traditional Tibetan Medicine Zuo-Mu-A Decoction(佐木阿汤)on the Blood Parameters and myocardium of High Altitude Polycythemia Model Rats

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Chinese Journal of Integrative Medicine 2017年第12期23卷 908-915页

作者： LU Meng-qian Nyima Tsring YU Tian-yuan WU Jian-cong Steven Wong CHEN Guo-yong Pasang Dekyi PAN Fan XIAN Si-tong Dorje Rinchen MAO Ying-qiu ZHANG Lin-feng YAO Bin-bin School of Acupuncture-Moxibustion and Tuina Beijing University of Chinese MedicineBeijing 100029China Tibetan Traditional Medical College Lhasa 850000China Department of Tuina Beijing Massage HospitalBeijing 100035China Information Center Beijing University of Chinese MedicineBeijing 100029China Tibet Academy of Tibetan Medicine Lhasa 850000China Center of Scientific Experiment Beijing University of Chinese MedicineBeijing 100029China

Objective: To explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction(佐木阿汤, ZMAD) on the blood parameters and myocardium of high altitude polycythemia(HAPC) model rats. Methods: Forty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L.(RRL) and ZMAD groups(10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL(20 mL/kg) and ZMAD(7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2’-deoxyguanosine(8-OHd G) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy. Results: Compared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHd G levels, and also increased the erythrocyte deformation index(P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group. Conclusion: ZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.

关键词： erythropoietin hematology myocardium high altitude polycythemia traditional medicine

Ventricular remodeling and intervention with losartan following rabbit chronic hibernating myocardium

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上海医学 2007年第S1期30卷 64-65页

作者： CHEN Yan, ZHANG Feilong, LUO Yukun, CHEN Lianglong. Union Hospital, Fujian Medical University & Fujian Provincial Institute of Coronary Disease, Fuzhou 350001, China

Objectives To explore the changes of myocyte and the interstitial collagen in a model of chronic hibernating myocardium (CHM) in rabbits, and to determine whether these alterations affect the cardiac function, and to further observe the effects of losartan on ventricular remodeling. Methods A left anterior descending (LAD) coronary artery stenosis was created and maintained for 4 weeks to create a CHM model in rabbits. Thirty-six rabbits were assigned to the following three groups(12 rabbits per group): CHM for 4 weeks(CHM group), low-dose of losartan intervention group for 4 weeks(LTl group, 10 mg·kg-1·d-1), high-dose of losartan intervention group for 4 weeks (LT2 group, 30 mg·kg-1·d-1); and 12 sham-operated rabbits served as controls (SO group). A microscopic imaging system (Image-Pro Plus, Olympus) was used to assess the Interstitial collagen volume fraction (ICVF) in myocardial sections with picrosirius-red staining, and a polarized light microscopy to qualitatively analysis the changes in the type and the proportion of collagen fibers, to semi-quantitatively score the proportion of collagen I to collagen III(PI/III). The expression of MMP-2, 9 and TIMP-2 was assessed by immunohistochemistry and western bloting. The myocyte apoptosis rate (Rapo) was calculated with TUNEL-staining. And echocardiography was performed to measure left ventricular end-systolic and end-diastolic diameter (LVESD, LVEED), and left ventricular short-axis fraction shortening (LVFS) and ejection fraction (LVEF). Results The animal model of CHM was induced successfully in 36 out of 39-rabbits and maintained for 28 days. Compared with the sham group, ICVF) was significantly increased (P<0.01) in CHM group; compared with CHM group, ICVF was significantly decreased (P<0.01,each) in LTl group and LT2 group, and the change were more remarkable in LT2 group, compared to LTl group(P<0.05). Compared with sham group, PI/IH was significantly increased (P < 0.01) in CHM group; compared with CHM group, PI/III was significantly decreased

关键词： remodeling myocardium myocyte collagen rabbit interstitial descending ejection LVESD TIMP

Study on the Cultivation of the Mycardium and myocardium Self-disciplining Cell Mass of Mouse Embryonic Bodies with their Own Feeder Layer

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Journal of Northeast Agricultural University(English Edition) 2003年第2期10卷 131-136页

作者： LIU Yan ZHANG Gui-xue CAO Yun-kao Northeast Agricultural University HarbinHeilongjiang150030PRC

myocardium tissue of Kunming mouse embryonic bodies was cultured with the feeder layer of their embryonic fibroblasts in TCM199.The results indicate that some piece of myocardium tissue can be cultured in the feeder layer;Their contracting frequency changed with the temperature and the morphology changed with the time;It was not all pieces of tissue with the same appearance that could contract,even though some of them grow well.

关键词： myocardium feeder layer mouse self-disciplining