• Title/Summary/Keyword: Cardiovascular model

Search Result 587, Processing Time 0.026 seconds

miR-23a Regulates Cardiomyocyte Apoptosis by Targeting Manganese Superoxide Dismutase

  • Long, Bo;Gan, Tian-Yi;Zhang, Rong-Cheng;Zhang, Yu-Hui
    • Molecules and Cells
    • /
    • v.40 no.8
    • /
    • pp.542-549
    • /
    • 2017
  • Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS into harmless products. In this study, we demonstrate that MnSOD is down-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial infarction induced by I/R injury. Further, we show that miR-23a directly regulates the expression of MnSOD. miR-23a regulates cardiomyocyte apoptosis by suppressing the expression of MnSOD. Our study reveals a novel model regulating cardiomyocyte apoptosis which is composed of miR-23a and MnSOD. Our study provides a new method to tackling apoptosis related cardiac diseases.

A Computational Model of Cytosolic and Mitochondrial [$Ca^{2+}$] in Paced Rat Ventricular Myocytes

  • Youm, Jae-Boum;Choi, Seong-Woo;Jang, Chang-Han;Kim, Hyoung-Kyu;Leem, Chae-Hun;Kim, Na-Ri;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.15 no.4
    • /
    • pp.217-239
    • /
    • 2011
  • We carried out a series of experiment demonstrating the role of mitochondria in the cytosolic and mitochondrial $Ca^{2+}$ transients and compared the results with those from computer simulation. In rat ventricular myocytes, increasing the rate of stimulation (1~3 Hz) made both the diastolic and systolic [$Ca^{2+}]$ bigger in mitochondria as well as in cytosol. As L-type $Ca^{2+}$ channel has key influence on the amplitude of $Ca^{2+}$ -induced $Ca^{2+}$ release, the relation between stimulus frequency and the amplitude of $Ca^{2+}$ transients was examined under the low density (1/10 of control) of L-type $Ca^{2+}$ channel in model simulation, where the relation was reversed. In experiment, block of $Ca^{2+}$ uniporter on mitochondrial inner membrane significantly reduced the amplitude of mitochondrial $Ca^{2+}$ transients, while it failed to affect the cytosolic $Ca^{2+}$ transients. In computer simulation, the amplitude of cytosolic $Ca^{2+}$ transients was not affected by removal of $Ca^{2+}$ uniporter. The application of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) known as a protonophore on mitochondrial membrane to rat ventricular myocytes gradually increased the diastolic [$Ca^{2+}$] in cytosol and eventually abolished the $Ca^{2+}$ transients, which was similarly reproduced in computer simulation. The model study suggests that the relative contribution of L-type $Ca^{2+}$ channel to total transsarcolemmal $Ca^{2+}$ flux could determine whether the cytosolic $Ca^{2+}$ transients become bigger or smaller with higher stimulus frequency. The present study also suggests that cytosolic $Ca^{2+}$ affects mitochondrial $Ca^{2+}$ in a beat-to-beat manner, however, removal of $Ca^{2+}$ influx mechanism into mitochondria does not affect the amplitude of cytosolic $Ca^{2+}$ transients.

Modeling and Simulation of the Cardiovascular System using DEVS formalism (DEVS 형식론을 적용한 심혈관 시스템의 모델링 및 시뮬레이션)

  • Cho, Y.J.;Son, K.S.;Nam, K.G.;Lee, Y.W.;Kim, K.N.;Choi, B.C.;Jun, K.R.
    • Proceedings of the KOSOMBE Conference
    • /
    • v.1996 no.11
    • /
    • pp.74-79
    • /
    • 1996
  • This paper describes a methodology for the development of models of discrete event system(DES). The methodology is based on transformation of continuous state space into discrete one to homomorphically represent dynamics of continuous processes in discrete events. This paper proposes a formal structure which can couple DES models within a framework. The structure employs the DEVS formalism for the DES models. The proposed formal structure has been applied to develop a DEVS model for the human cardiovascular system. For this, the cardiac cycle is partitioned into a set of phases based on events identified through VisSim simulation in the CS of the electrical analog model. VisSim is the simulation tool of visual environment for developing continuous, discrete, and hybrid system models and performing dynamic simulation. For each phase, a CS of the electrical analog model for the cardiovascular system has been simulated by VisSim 2.0. To validate this model, first develop the DEVS model, then simulate the model in the DEVSIM++ environment. It has same simulation results for the data obtained from the CS simulation using VisSim. The comparison shows that the DEVS model represents dynamics of the human heart system at each phase of cardiac cycle.

  • PDF

Antihyperlipidemic and Antioxidant Effects of Insamsansa-eum (Renshenshanzha-yin) in Hypercholesterolemic Rats

  • Kim, Young-Suk;Kang, Kyoung-Suk;Jung, Woo-Sang;Moon, Sang-Kwan;Park, Jung-Mi;Ko, Chang-Nam;Cho, Ki-Ho;Bae, Hyung-Sup;Park, Seong-Uk
    • The Journal of Korean Medicine
    • /
    • v.27 no.4
    • /
    • pp.96-104
    • /
    • 2006
  • Insamsansa-eum (Renshenshanzha-yin, ISE) is a new medicine developed to prevent and treat atherosclerotic diseases. To explore antiatherosclerotic effects of ISE, we evaluated the effects of ISE on serum lipids of hypercholesterolemic rats in vivo, as well as its antioxidant activities in vitro. In vitro, ISE showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide radical scavenging activities, and inhibited hemolysis induced by 2,2' -azobis-2-amidinopropane dihydrochloride (AAPH) in a dose-dependent manner. In vivo, ISE significantly inhibited increase of total cholesterol (TC), low-density lipoprotein cholesterol (LDL) and triglyceride (TG) values in both high cholesterol diet and Triton WR-1339 models. It also significantly inhibited decrease of high-density lipoprotein cholesterol (HDL) value in the high cholesterol diet model. Collectively, our data suggest that ISE has the potential to control the risk of atherosclerosis development.

  • PDF

Spatial analysis of $PM_{10}$ and cardiovascular mortality in the Seoul metropolitan area

  • Lim, Yu-Ra;Bae, Hyun-Joo;Lim, Youn-Hee;Yu, Seungdo;Kim, Geun-Bae;Cho, Yong-Sung
    • Environmental Analysis Health and Toxicology
    • /
    • v.29
    • /
    • pp.5.1-5.7
    • /
    • 2014
  • Objectives Numerous studies have revealed the adverse health effects of acute and chronic exposure to particulate matter less than $10{\mu}m$ in aerodynamic diameter ($PM_{10}$). The aim of the present study was to examine the spatial distribution of $PM_{10}$ concentrations and cardiovascular mortality and to investigate the spatial correlation between $PM_{10}$ and cardiovascular mortality using spatial scan statistic (SaTScan) and a regression model. Methods From 2008 to 2010, the spatial distribution of $PM_{10}$ in the Seoul metropolitan area was examined via kriging. In addition, a group of cardiovascular mortality cases was analyzed using SaTScan-based cluster exploration. Geographically weighted regression (GWR) was applied to investigate the correlation between $PM_{10}$ concentrations and cardiovascular mortality. Results An examination of the regional distribution of the cardiovascular mortality was higher in provincial districts (gu) belonging to Incheon and the northern part of Gyeonggi-do than in other regions. In a comparison of $PM_{10}$ concentrations and mortality cluster (MC) regions, all those belonging to MC 1 and MC 2 were found to belong to particulate matter (PM) 1 and PM 2 with high concentrations of air pollutants. In addition, the GWR showed that $PM_{10}$ has a statistically significant relation to cardiovascular mortality. Conclusions To investigate the relation between air pollution and health impact, spatial analyses can be utilized based on kriging, cluster exploration, and GWR for a more systematic and quantitative analysis. It has been proven that cardiovascular mortality is spatially related to the concentration of $PM_{10}$.

The Impact of an Attending Intensivist on the Clinical Outcomes of Patients Admitted to the Cardiac Surgical Intensive Care Unit after Coronary Artery Bypass Grafting

  • Kim, Dong Jung;Sohn, Bongyeon;Kim, Hakju;Chang, Hyoung Woo;Lee, Jae Hang;Kim, Jun Sung;Lim, Cheong;Park, Kay-Hyun
    • Journal of Chest Surgery
    • /
    • v.53 no.1
    • /
    • pp.8-15
    • /
    • 2020
  • Background: We aimed to investigate the associations of critical care provided in a cardiac surgical intensive care unit (CSICU) staffed by an attending intensivist with improvements in intensive care unit (ICU) quality and reductions in postoperative complications. Methods: Patients who underwent elective isolated coronary artery bypass grafting (CABG) between January 2007 and December 2012 (the control group) were propensity-matched (1:1) to CABG patients between January 2013 and June 2018 (the intensivist group). Results: Using propensity score matching, 302 patients were extracted from each group. The proportion of patients with at least 1 postoperative complication was significantly lower in the intensivist group than in the control group (17.2% vs. 28.5%, p=0.001). In the intensivist group, the duration of mechanical ventilation (6.4±13.7 hours vs. 13.7±49.3 hours, p=0.013) and length of ICU stay (28.7±33.9 hours vs. 41.7±90.4 hours, p=0.018) were significantly shorter than in the control group. The proportions of patients with prolonged mechanical ventilation (2.3% vs. 7.6%, p=0.006), delirium (1.3% vs. 6.3%, p=0.003) and acute kidney injury (1.3% vs. 5.3%, p=0.012) were significantly lower in the intensivist group than in the control group. Conclusion: A transition from an open ICU model with trainee coverage to a closed ICU model with attending intensivist coverage can be expected to yield improvements in CSICU quality and reductions in postoperative complications.

Cardiovascular Protective Effects of the n-Butanol Fraction from Glehnia littoralis Fr. Schm. in a High-Fat-Diet Mouse Model and Its Composition (고지방식이 마우스 동물모델에서 갯방풍 부탄올 분획물의 심혈관 보호 효과 및 주요 성분)

  • Lim, Hyun-Jin;Kwon, Hansol;Cho, Hyun-Woo;An, Byeong-Kwan;Cho, Jung-Hee;Oak, Min-Ho;Kim, Hyun Jung;Han, Dong-Sul
    • Korean Journal of Pharmacognosy
    • /
    • v.47 no.1
    • /
    • pp.49-54
    • /
    • 2016
  • In our search for natural products affecting blood circulation, the n-butanol fraction from whole plant of Glehnia littoralis Fr. Schm. (GLB) improved blood lipid parameters, and ameliorated obesity in high-fat-diet (HFD)-fed C57BL/6 mouse model. Hyperlipidemia was induced by high-fat-diet for 4 weeks, and then GLB was orally administrated with 400 mg/kg/day for 4 weeks. GLB-treated group showed that the gain in body weight was significantly attenuated, the levels of total cholesterol and triglyceride significantly lowered on blood chemical analysis, and significantly prolonged the mice bleeding time when compared with those of HFD control group. Concomitantly, phytochemical composition of GLB was investigated by HPLC-hyphenated spectroscopy, and two major phenolic compounds, rutin and chlorogenic acid were identified in the GLB. Taken together, these results indicate that GLB has cardiovascular protective effects and could be a natural medicine candidate for the prevention of cardiovascular disease.

A Study for Changes of Blood Pressure and Heart Rate by Acupressure to Acupoints in Rat Model of Hemorrhagic Shock (출혈성 쇼크 흰쥐 모델에서 경혈 지압이 혈압과 심박수 변화에 미치는 영향)

  • Yang, Seung-Bum;Byun, Sin-Kyu;Kim, Jae-Hyo
    • Korean Journal of Acupuncture
    • /
    • v.33 no.2
    • /
    • pp.58-66
    • /
    • 2016
  • Objectives : In order to find a possible non-invasive manipulation tool for maintenance of the cardiovascular functions in hemorrhagic shock, this study was aimed at evaluating effects of acupoints acupressure on the changes in blood pressure and heart rate from an animal model of hemorrhagic shock. Methods : In adult Sprague-Dawley rats, hemorrhagic shock was induced by a withdrawal of arterial blood from the femoral artery with volume of 0.8 ml per 100 g of body weight using peristaltic syringe pump. We applied the acupressure with a pressure oscillator to tail as a control and 2 different acupoints of sobu(HT8), youngchun(KI1) under 3 different conditions : 1) normal arterial blood pressure without bleeding, 2) at the beginning of bleeding, and finally 3) hemorrhagic shock. Results : Under normal arterial blood pressure without hemorrhage, there was a significant increase in systolic and diastolic blood pressures by the acupressure to the tail, HT8 and especially KI1 for 30 sec compared with before acupressure. Under hemorrhagic shock condition, the tail acupressure had minimal changes in cardiovascular parameters. Either the HT8 or KI1 acupressure resulted in a significant increase in arterial pressure but did not heart rate. At the beginning of bleeding, tail acupressure failed to change the reduction of arterial pressure and heart rate. However, there was a significant increase in blood pressure and heart rate following either the HT8 or especially KI1 acupressure. Conclusions : HT8 and KI1 acupressure affected cardiovascular signs but tail acupressure did not in rat model of hemorrhagic shock. These experimental data suggest that a acupressure with a pressure oscillator to HT8 or KI1 can be one of alternative emergency manipulations to ameliorate compromised cardiovascular functions under hemorrhagic shock condition.

Targeted Efficacy of Dihydroartemisinin for Translationally Controlled Protein Expression in a Lung Cancer Model

  • Liu, Lian-Ke;Wu, Heng-Fang;Guo, Zhi-Rui;Chen, Xiang-Jian;Yang, Di;Shu, Yong-Qian;Zhang, Ji-Nan
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.6
    • /
    • pp.2511-2515
    • /
    • 2014
  • Objective: Lung cancer is one of the malignant tumors with greatest morbidity and mortality around the world. The keys to targeted therapy are discovery of lung cancer biomarkers to facilitate improvement of survival and quality of life for the patients with lung cancer. Translationally controlled tumor protein (TCTP) is one of the most overexpressed proteins in human lung cancer cells by comparison to the normal cells, suggesting that it might be a good biomarker for lung cancer. Materials and Methods: In the present study, the targeted efficacy of dihydroartemisinin (DHA) on TCTP expression in the A549 lung cancer cell model was explored. Results and Conclusions: DHA could inhibit A549 lung cancer cell proliferation, and simultaneously up-regulate the expression of TCTP mRNA, but down-regulate its protein expression in A549 cells. In addition, it promoted TCTP protein secretion. Therefore, TCTP might be used as a potential biomarker and therapeutic target for non-small cell lung cancers.

Traditional oriental herbal medicine, Jukyeoondam-tang, occludes aconitine-induced ventricular arrhythmia in hearts

  • Ha, Ki-Chan;Chae, Han-Jung;Piao, Cheng-Shi;Chae, Soo-Uk;Kim, Hyung-Ryong;Chae, Soo-Wan
    • Advances in Traditional Medicine
    • /
    • v.4 no.3
    • /
    • pp.157-161
    • /
    • 2004
  • We showed the effects of the traditional herbal medicine, Jukyeoondam-tang (JO-T, Zhu-ru-Wen-Dan-Tang in Chinese), on ventricular arrhythmia induced by aconitine. Electrophysiological experiments with conventional microelectrode techniques revealed that JO-T potently suppressed the aconitine-induced arrhythmias in ventricular strips of the rat. In the aconitine-induced arrhythmia model of the rat, pretreatment with JO-T $(100\;{\mu}g/ml)$ completely occluded the appearance of ventricular tachyarrhythmia (VT) or ventricular fibrillation (VF) induced by aconitine. Furthermore, the aconitine-induced ventricular arrhythmia was occluded by $Na^+$ channel blocker quinidine but was not occluded by $K^+$ channel blocker glibenclamide $(3\;{\mu}mol/L)\;and\;Ca^{2+}$ channel blocker nifedipine $(10\;{\mu}mol/L)$. We also confirmed the effect of JO-T in the ischemia-reperfusion (I/R)-induced arrhythmia model of the rat. JO-T did not affect the I/R-induced arrhythmias in rats. JO-T may alleviate the risk of ventricular arrhythmias following aconitine. These results suggest that JO-T is a potent antiarrhythmic drug having a$Na^+$ channel-blocking action.