Oxidized low density lipoprotein and peroxisome proliferator-activated receptor α induced endogenous fibroblast growth factor 21 upregulation is protective against apoptosis in cardiac endothelial cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of peroxisome proliferator-activated receptor (PPAR)α agonist bezafibrate and oxidized low density lipoprotein (ox-LDL) on fibroblast growth factor 21 (FGF21) expression and apoptosis in cardiac endothelial cells.</p><p><b>METHODS</b>The mRNA level of FGF21 was determined by real time-PCR and the protein concentration of FGF21 in culture media was detected by enzyme-linked immunosorbent assay in cultured cardiac microvascular endothelial cells (CMECs) incubated with 10, 50, 100 µg/ml ox-LDL, 50, 100 or 200 µmol/L bezafibrate alone or in combination with 100 µg/ml ox-LDL. CMECs apoptosis in various treatment groups was also determined.</p><p><b>RESULTS</b>FGF21 mRNA and protein expressions were significantly upregulated in proportion to increased ox-LDL, and 200 µmol/L bezafibrate alone also significantly upregulated FGF21 expression and CMECs apoptosis was significantly reduced in 200 µmol/L bezafibrate + 100 µg/ml ox-LDL group compared to 100 µg/ml ox-LDL group (P < 0.05).</p><p><b>CONCLUSIONS</b>Our data suggest that bezafibrate and ox-LDL induced upregulation of FGF21 might mediate the protective effect against apoptosis. Endogenous FGF21 could thus play important roles in improving the endothelial function at the early stage of atherosclerosis and slowing the development of coronary heart disease.</p>

Fibroblast growth factor 21 as a possible endogenous factor inhibits apoptosis in cardiac endothelial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fibroblast growth factor 21 (FGF21) is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection factor.</p><p><b>METHODS</b>The present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein (ox-LDL), and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells (CMECs) were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMECs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 levels.</p><p><b>RESULTS</b>The secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 µmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis (P < 0.05).</p><p><b>CONCLUSIONS</b>FGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.</p>

Protective effects of 11,12-epoxyeicosatrienoic acid preconditioning and postconditioning on myocardial ischemia/reperfusion injury in rats / 生理学报

To explore the effects of 11,12-epoxyeicosatrienoic acid (11,12-EET) preconditioning and postconditioning on myocardial ischemia/reperfusion (IR) injury in rats, the IR injury model was built by stopping perfusion for 40 min followed by reperfusion for 30 min, and the changes of mitochondrial functions, myocardial metabolism and function were measured. Langendorff-perfused isolated rat hearts were divided into 4 groups: control group, persistently perfused with Krebs-Henseleit (K-H) fluid for 100 min; IR group, stopped perfusion for 40 min followed by reperfusion for 30 min; Pre-EET group, preconditioned with 6.24×10(-9) mol/L 11,12-EET for 5 min twice before subjected to ischemia; Post-EET group, postconditioned with 6.24×10(-9) mol/L 11,12-EET for 30 s twice before reperfusion. The computer-based electrophysiological recording system was used to measure the changes of maximal rate of the pressure increase in contract phase (+dp/dt(max)), maximal rate of the pressure decrease in diastole phase of heart (-dp/dt(max)), left ventricular end-diastolic pressure (LVEDP) and difference of left ventricular pressure (DLVP). The activities of lactate dehydrogenase (LDH) in effluent, Ca(2+)-ATPase, Na(+)-K(+)-ATPase and succinate dehydrogenase (SDH) in mitochondria were measured with colorimetry method; superoxide dismutase (SOD) activity was measured with hydroxylamine method and malondialdehyde (MDA) content in myocardial tissues was measured with TBA method. The results showed that: (1) Compared with that in the control group, the myocardial functions, the values of SOD, SDH and Na(+)-K(+)-ATPase were decreased in IR group (P<0.05); the values of LDH, MDA and Ca(2+)-ATPase were increased (P<0.05) in IR group. (2) Compared with that in IR group, the values of SDH and Na(+)-K(+)-ATPase were increased (P<0.05) and the value of Ca(2+)-ATPase was decreased (P<0.05) in both Pre-EET and Post-EET groups. But no significant differences were detected between Pre-EET and Post-EET groups. (3) Compared with IR treatment, both 11,12-EET preconditioning and postconditioning caused significant decreases in MDA content and leakage of LDH, amendment of heart functions and increases in SOD activity (P<0.05). But there were no significant differences between 11,12-EET preconditioning and postconditioning. These results indicate that 11,12-EET preconditioning and postconditioning can protect myocardium from IR injury by improving mitochondrial functions, up-regulating the activities of Na(+)-K(+)-ATPase and SDH, and down-regulating the activity of Ca(2+)-ATPase in mitochondria. Moreover, 11,12-EET preconditioning and postconditioning also elevate the activity of SOD and reduce the content of MDA, suggesting that 11,12-EET can depress the oxidative stress in IR rat heart.

Effects of 11, 12-epoxyeicosatrienoic acid preconditioning and postconditioning on Ca(2+)- handling proteins in myocardial ischemia/reperfusion injury in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effects of 11, 12-epoxyeicosatrienoic acid (11, 12-EET) preconditioning and postconditioning on Ca(2+)-handling proteins in myocardial ischemia/reperfusion (IR) injury in rats and reveal the effects and mechanism of 11, 12-EET on cardioprotection. METHODS The IR injury model was built by stopping perfusion for 40 minutes followed by reperfusion for 30 minutes. The isolated Langendorff-perfused rat hearts were divided into 4 groups: control group, IR group, EET preconditioning (Pre-EET) group and EET postconditioning (Post-EET) group. The computer-based electrophysiological recorder system was used to measure the changes of the maximal rate of pressure increased in the contraction phase (+dp/dt(max)), the maximal rate of pressure decreased in the diastole phase (-dp/dt(max)), the left ventricular end diastolic pressure (LVEDP) and the difference of left ventricular pressure (delta LVP). The activity of Ca(2+)-ATPase in sarcoplasmic reticulum was measured with colorimetric method. Reverse transcription-polymerase chain reaction was used to assess the gene expression of C(a2+)-handling protein [sarcoplasic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), ryanodine receptor type 2 (RyR,), and 1, 4, 5-trisphosphate inositol receptor type 2 (IP3 R2) ] mRNAs level.</p><p><b>RESULTS</b>Compared with IR group, the myocardial functions, the value of Ca(2+)-ATPase, and the expressions of IP3 R2 mRNA were significantly increased and the expression of PLB mRNA was significantly decreased in both Pre-EET group and Post-EET group (P < 0.05, P < 0.01). And the expression of SERCA mRNA was significantly increased in Pre-EET group (P < 0. 05). However, no significant differences were detected between Pre-EET and Post-EET groups. Moreover, the expression of RyR2 mRNA was not significantly different among all groups.</p><p><b>CONCLUSIONS</b>11, 12-EET preconditioning and post-conditioning can protect myocardium from IR injury by elevating the activity of Ca(2+)-ATPase in sarcoplasmic reticulum, up-regulating the expression of IP3 R2 mRNA, and down-regulating the expression of PLB mRNA. Moreover, up-regulating the expression of SERCA mRNA maybe one of mechanisms of 11, 12-EET preconditioning on cardio protection against IR injury.</p>

Effect of 11, 12-epoxyeicosatrienoic acid on nitric oxide synthase of ischemia-reperfusion myocardium in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the effect of 11,12-epoxyeicosatrienoic acid (11,12-EET) on nitric oxide synthase (NOS) in myocardial ischemia/reperfusion injury and explore the protective role of NOS in myocardium.</p><p><b>METHODS</b>Rat myocardial ischemia/reperfusion model was produced by ischemia for 60 minutes and reperfusion for 30 minutes. Rats were divided into 5 groups: 11,12-EET ischemia/reperfusion groups (including EET1, EET2, and EET3 groups), EET control group, ischemia/reperfusion group, sham operation group, and control group. Changes of the maximal rates of rise and decrease of left ventricular pressure (+/-dp/dtmax) were observed. Activities of inducible nitric oxide synthase (iNOS) and constrictive nitric oxide synthase (cNOS) in myocardium were measured with chemocolorimetry.</p><p><b>RESULTS</b>During both ischemia period (60 min) and reperfusion period (30 min), +/-dp/dtmax was significantly lower in ischemia/reperfusion group than in sham operation group (P < 0.01), and was significantly higher in EET1, EET2 and EET3 groups than in ischemia/reperfusion group (P < 0.01). cNOS level was significantly lower in ischemia/reperfusion group than in sham operation group, was significantly higher in EET1, EET2 and EET3 groups than in sham operation group (P < 0.01), and was significantly higher in EET2 group than in EET group (P < 0.01). iNOS level was significantly higher in sham operation group than in EET control group (P < 0.05), was significantly higher in ischemia/ reperfusion group than in sham operation group (P < 0.01), and was significantly lower in EET1, EET2 and EET3 groups than in ischemia/reperfusion group (P < 0.01).</p><p><b>CONCLUSION</b>Exogenous 11,12-EET can improve ischemia/reperfusion injury, which may be related with the changes of NOS isozymes.</p>

Clinical analysis of 234 cases of mitral valve replacement in beating heart / 第三军医大学学报

Objective　To introduce the technique of mitral v alve replacements in beating heart, and review the clinical experience in 234 ca ses of operation. Methods　A total of 234 patients of mitral val ve replacement in beating heart with mild hypothermic extracorporeal circulation (30～32 ℃) were reviewed. Results　 The procedures underwe nt fluently and only 2(0.85%) died early postoperatively. No low cardiac output , arrhythmia and cer ebral embolism complications was found. Conclusion　Results sugg ested that mitral valve replacement in beating heart is a safe and available method and is good in extenuating myocardial and pulmonary i njury from ischemia-reperfusion and deep hypothermia.

On-pump, beating-heart intracardiac procedures for congenital heart disease with severe pulmonary hypertension / 第三军医大学学报

Objective　To compare the clinical efficiency of intracardiac procedures on traditional cardioplegic arrested-heart and on-pu mp beating-heart for congenital heart disease (CHD) with severe pulmonary hyper tension. Methods　Among all 153 cases, 95 cases underwent operat ions on cardioplegic arrested-heart, while 58 on-pump beating-heart. In arres ted-heart group, 79 cases with ventricular septal defect (VSD), 13 with atria l septal defect (ASD) and 3 with patent ductus arteriosus (PDA) were examined whi le in beating-heart group, 43 cases with VSD, 10 with ASD, and 5 with PDA were examined. Results　There were 12 cases of operative death (12.6%) and 8 of tracheotomy (8.4%) in heart arrested group. No operative death and tracheotomy in beating-heart group. 141 patients were followed up for 3 months to 10 year s with good recovery. There were 2 cases of right heart function failure six yea rs later in arrested-heart group. Conclusion　Results sugges t that on-pump beating-heart technique is superior to traditional cardiopl egic arrested-heart for CHD with severe pulmonary hypertesion. The cause might be t hat on-pump beating-heart intracardiac operation is more effective in cardio pulmon ary protection.

Clinical analysis of on-pump, beating-heart intracardiac proc edures in 1 032 cases / 第三军医大学学报

Objective　To improve intracardiac operation skil ls on bea-ting-heart with mild hypothermic cardiopulmonary bypass (On pump beating-heart technique), and to review the clinical experience in 1 032 c ases. Methods　A total of 1 032 cases of intracardiac operatio ns on pump beating-heart from November 1997 to September 2000 were reviewed. Of them, 714 cases were congenital heart diseases (CHD), and 318 cases were valvul ar heart diseases (VHD). The technique was improved by establishing simultaneous left atrium and ventricle suction and integrating sequential de-airing procedu re. Results　The operative mortality was 2.33% (24/1 032), the m ortality was 2.7% (19/714) in cases with CHD, and 1.6% (5/318) in those with VHD. There was no pati ent complicated with systemic air embolism or permanent atrioventricular conduct ion block. Conclusion　Results suggested that intracardiac procedures on pump beating-heart with mild hypothermic cardiopnlmonary bypass is safe and available in patients with CHD or VHD. It might extenuate the heart and lung injury by hypothermia and ischemia-reperfusion during cardiopulmonary bypass. Cardiac conducting block might be prevented during operation.

Clinical analysis of 234 cases of mitral valve replacement in beating heart / 第三军医大学学报

Objective　To introduce the technique of mitral v alve replacements in beating heart, and review the clinical experience in 234 ca ses of operation. Methods　A total of 234 patients of mitral val ve replacement in beating heart with mild hypothermic extracorporeal circulation (30～32 ℃) were reviewed. Results　 The procedures underwe nt fluently and only 2(0.85%) died early postoperatively. No low cardiac output , arrhythmia and cer ebral embolism complications was found. Conclusion　Results sugg ested that mitral valve replacement in beating heart is a safe and available method and is good in extenuating myocardial and pulmonary i njury from ischemia-reperfusion and deep hypothermia.

On-pump, beating-heart intracardiac procedures for congenital heart disease with severe pulmonary hypertension / 第三军医大学学报

Objective　To compare the clinical efficiency of intracardiac procedures on traditional cardioplegic arrested-heart and on-pu mp beating-heart for congenital heart disease (CHD) with severe pulmonary hyper tension. Methods　Among all 153 cases, 95 cases underwent operat ions on cardioplegic arrested-heart, while 58 on-pump beating-heart. In arres ted-heart group, 79 cases with ventricular septal defect (VSD), 13 with atria l septal defect (ASD) and 3 with patent ductus arteriosus (PDA) were examined whi le in beating-heart group, 43 cases with VSD, 10 with ASD, and 5 with PDA were examined. Results　There were 12 cases of operative death (12.6%) and 8 of tracheotomy (8.4%) in heart arrested group. No operative death and tracheotomy in beating-heart group. 141 patients were followed up for 3 months to 10 year s with good recovery. There were 2 cases of right heart function failure six yea rs later in arrested-heart group. Conclusion　Results sugges t that on-pump beating-heart technique is superior to traditional cardiopl egic arrested-heart for CHD with severe pulmonary hypertesion. The cause might be t hat on-pump beating-heart intracardiac operation is more effective in cardio pulmon ary protection.

Clinical analysis of on-pump, beating-heart intracardiac proc edures in 1 032 cases / 第三军医大学学报

Objective　To improve intracardiac operation skil ls on bea-ting-heart with mild hypothermic cardiopulmonary bypass (On pump beating-heart technique), and to review the clinical experience in 1 032 c ases. Methods　A total of 1 032 cases of intracardiac operatio ns on pump beating-heart from November 1997 to September 2000 were reviewed. Of them, 714 cases were congenital heart diseases (CHD), and 318 cases were valvul ar heart diseases (VHD). The technique was improved by establishing simultaneous left atrium and ventricle suction and integrating sequential de-airing procedu re. Results　The operative mortality was 2.33% (24/1 032), the m ortality was 2.7% (19/714) in cases with CHD, and 1.6% (5/318) in those with VHD. There was no pati ent complicated with systemic air embolism or permanent atrioventricular conduct ion block. Conclusion　Results suggested that intracardiac procedures on pump beating-heart with mild hypothermic cardiopnlmonary bypass is safe and available in patients with CHD or VHD. It might extenuate the heart and lung injury by hypothermia and ischemia-reperfusion during cardiopulmonary bypass. Cardiac conducting block might be prevented during operation.