Background Renin-angiotensin-aldosterone system has been demonstrated to be associated with both congestive heart failure （CHF） and atrial fibrillation （AF）. This study investigated the effects of spironolactone, ...Background Renin-angiotensin-aldosterone system has been demonstrated to be associated with both congestive heart failure （CHF） and atrial fibrillation （AF）. This study investigated the effects of spironolactone, a kind of aldosterone antagonist, on atrial electrical remodeling and fibrosis in CHF dogs induced by chronic rapid ventricular pacing. Methods Twenty one dogs were randomly divided into sham-operated group, control group, and spironolactone group. In control group and spironolactone group, dogs were ventricular paced at 220 beats per minute for 6 weeks. Additionally, spironolactone at 15 mg.kgl.d1 was given to dogs 1 week before rapid ventricular pacing until pacing stopped. Transthoracic and transoesophageal echocardiographic examinations were performed to detect structural and functional changes of the atrium. Swan2 Ganz floating catheters were used to measure hemadynamics variances. Atrial effective refractory period （AERP）, AERP dispersion （AERPd） conduction velocity （CV） were determined. The inducib atrial fibrosis was quantified with Masson staining. intra- and inter-atrium conduction time （CT） and intra-atrium ity and duration of AF were also measured in all groups. Finally, Results AERP did not change significantly after dogs were ventricular paced for 6 weeks. However, AERPd, intra- and inter-atrium CT increased significantly, and CV decreased apparently, which was negatively correlated to the atrial fibrosis （r=-0.74, P〈0.05）. Simultaneously, left atriums were enlarged and cardiac hemadynamics worsened in pacing dogs. Although spironolactone could not affect cardiac hemadynamics effectively, it can obviously improve left atrial ejection fraction （P〈0.05）. Spironolactone treatment did not alter AERP duration, but this medicine dramatically decreased AERPd （P〈0.05）, shortened intra- and inter-atrium conduction time （P〈0.05）, and increased atrium CV. Moreover, spironolactone decreased the inducibility and duration of AF （P〈0.05）, as well as at展开更多
Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell proliferation.However,the effects and mechanisms of Pae on chronic he...Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell proliferation.However,the effects and mechanisms of Pae on chronic heart failure(CHF)remain unclear.This study was conducted to assess the effects and mechanisms of Pae on myocardial fibrosis in isoprenaline(Iso)-induced CHF rats.Pae(20 mgkg)was intragastrically administrated to CHF rats for 6 weeks.Cardiac structure and function were assessed.The protein and mRNA levels of transforming growth factorβ1(TGF-β1)and p38 were detected.C ompared to Iso group,Pae could alleviate myocardial fbrosis and improve cardiac function in CHF rats.The levels of collagen volume fraction(13.75%+3.77%vs.30.97%+4.22%,P<0.001)and perivascular collagen volume area(14.32%+2.50%v8.28.31%+3.16%,P<0.001)were significantly reduced in Pae group as compared with those in Iso group.The expression of TGF-BI protein(0.30+0.07 vs.0.66+0.07,P<0.05)and mRNA(3.51+0.44 vs.7.58+0.58,P<0.05)decreased significantly in Pac group as compared with that in Iso group.The expression of p38 protein(0.36+0.12 vs.0.81+0.38,P<0.05)and mRNA(3.84+0.05 vs.4.40+0.17,P<0.05)also decreased markedly in Pae group as compared with that in Iso group.Pae could attenuate myocardial fibrosis and improve cardiac function in CHF rats by down-regulating the p38 MAPK signaling pathway.展开更多
Background Diabetic myocardiopathy is characterized by myocardial interstitial fibrosis and cardiac dysfunction. Statins were found to exert protective effects on cardiovascular disease by suppressing activation of sm...Background Diabetic myocardiopathy is characterized by myocardial interstitial fibrosis and cardiac dysfunction. Statins were found to exert protective effects on cardiovascular disease by suppressing activation of small G proteins, independently of their lipid-lowering effect. The study investigated the effect of fluvastatin on myocardial interstitial fibrosis, cardiac function and mechanism of its action in diabetic rats. Methods Twenty-four male SD rats were randomly assigned to 3 groups： control rats （n=-8）, streptozotocin （STZ）-induced diabetic rats （n=8）, and diabetic rats treated with fluvastatin （administered fluvastatin orally, 10 mg/kg body weight per day, n=-8）. Twelve weeks later, miniature cardiac catheter was inserted into the left ventricle to conduct hemodynamic examination. Then myocardium tissues were collected, collagen content was detected by picro-sirius red staining, real-time quantitative reverse transcription polymerase chain reaction （RT-PCR） was used to detect the mRNA expression of connective tissue growth factor （CTGF）, and Western blotting was used to detect the protein expression of CTGF. Rho activity was determined by pull-down assay. Results After 12 weeks, the left ventricular systolic pressure （LVSP） and maximum rate of left ventricular （LV） pressure rise and fall （＋dP/dt max and -dP/dt max） were significantly lower and left ventricular end diastolic pressure （LVEDP） was higher in the diabetic rats than those in the control rats （P 〈0.01）. Moreover, in LV myocardial tissue of diabetic rats the collagen content, fibronectin, mRNA and protein expression of CTGF and the activity of RhoA were all significantly increased compared with the control rats （P 〈0.01）. Administration of fluvastain obviously improved the cardiac function of diabetic rats, attenuated fibronectin expression, mRNA and protein expression of CTGF and the activity of RhoA in LV myocardium of diabetic rats. Conclusions Fluvastatin attenuates cardiac dysfunction展开更多
micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising bi...micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease mi RNAs have been proven to be reliable diagnostic biomarkers for different disease entities. In cardiac fibrosis(CF) and heart failure(HF) dysregulated circulating mi RNAs have been identified,indicating their promising applicability as diagnostic biomarkers. Some mi RNAs were successfully tested in risk stratification of HF implementing their potential use as prognostic biomarkers. In this respect mi RNAs might soon be implemented in diagnostic clinical routine. In the young field of mi RNA based research advances have been made in identifying mi RNAs as potential targets for the treatment of experimental CF and HF. Promising study results suggest their potential future application as therapeutic agents in treatment of cardiovascular disease. This article summarizes the current state of the various aspects of mi RNA research in the field of CF and HF with reduced ejection fraction as well as preserved ejection fraction. The review provides an overview of the application of circulating mi RNAs as biomarkers in CF and HF and current approaches to therapeutically utilize mi RNAs in this field of cardiovascular disease.展开更多
文摘Background Renin-angiotensin-aldosterone system has been demonstrated to be associated with both congestive heart failure （CHF） and atrial fibrillation （AF）. This study investigated the effects of spironolactone, a kind of aldosterone antagonist, on atrial electrical remodeling and fibrosis in CHF dogs induced by chronic rapid ventricular pacing. Methods Twenty one dogs were randomly divided into sham-operated group, control group, and spironolactone group. In control group and spironolactone group, dogs were ventricular paced at 220 beats per minute for 6 weeks. Additionally, spironolactone at 15 mg.kgl.d1 was given to dogs 1 week before rapid ventricular pacing until pacing stopped. Transthoracic and transoesophageal echocardiographic examinations were performed to detect structural and functional changes of the atrium. Swan2 Ganz floating catheters were used to measure hemadynamics variances. Atrial effective refractory period （AERP）, AERP dispersion （AERPd） conduction velocity （CV） were determined. The inducib atrial fibrosis was quantified with Masson staining. intra- and inter-atrium conduction time （CT） and intra-atrium ity and duration of AF were also measured in all groups. Finally, Results AERP did not change significantly after dogs were ventricular paced for 6 weeks. However, AERPd, intra- and inter-atrium CT increased significantly, and CV decreased apparently, which was negatively correlated to the atrial fibrosis （r=-0.74, P〈0.05）. Simultaneously, left atriums were enlarged and cardiac hemadynamics worsened in pacing dogs. Although spironolactone could not affect cardiac hemadynamics effectively, it can obviously improve left atrial ejection fraction （P〈0.05）. Spironolactone treatment did not alter AERP duration, but this medicine dramatically decreased AERPd （P〈0.05）, shortened intra- and inter-atrium conduction time （P〈0.05）, and increased atrium CV. Moreover, spironolactone decreased the inducibility and duration of AF （P〈0.05）, as well as at
基金This study was supported by grants from Scientific Research Development Program of North Sichuan Medical College(No.CBY16-A-ZD10)Nanchong Government-University Strategic Cooperation Project in Science and Technology(No.18SXHZ0505).
文摘Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell proliferation.However,the effects and mechanisms of Pae on chronic heart failure(CHF)remain unclear.This study was conducted to assess the effects and mechanisms of Pae on myocardial fibrosis in isoprenaline(Iso)-induced CHF rats.Pae(20 mgkg)was intragastrically administrated to CHF rats for 6 weeks.Cardiac structure and function were assessed.The protein and mRNA levels of transforming growth factorβ1(TGF-β1)and p38 were detected.C ompared to Iso group,Pae could alleviate myocardial fbrosis and improve cardiac function in CHF rats.The levels of collagen volume fraction(13.75%+3.77%vs.30.97%+4.22%,P<0.001)and perivascular collagen volume area(14.32%+2.50%v8.28.31%+3.16%,P<0.001)were significantly reduced in Pae group as compared with those in Iso group.The expression of TGF-BI protein(0.30+0.07 vs.0.66+0.07,P<0.05)and mRNA(3.51+0.44 vs.7.58+0.58,P<0.05)decreased significantly in Pac group as compared with that in Iso group.The expression of p38 protein(0.36+0.12 vs.0.81+0.38,P<0.05)and mRNA(3.84+0.05 vs.4.40+0.17,P<0.05)also decreased markedly in Pae group as compared with that in Iso group.Pae could attenuate myocardial fibrosis and improve cardiac function in CHF rats by down-regulating the p38 MAPK signaling pathway.
文摘Background Diabetic myocardiopathy is characterized by myocardial interstitial fibrosis and cardiac dysfunction. Statins were found to exert protective effects on cardiovascular disease by suppressing activation of small G proteins, independently of their lipid-lowering effect. The study investigated the effect of fluvastatin on myocardial interstitial fibrosis, cardiac function and mechanism of its action in diabetic rats. Methods Twenty-four male SD rats were randomly assigned to 3 groups： control rats （n=-8）, streptozotocin （STZ）-induced diabetic rats （n=8）, and diabetic rats treated with fluvastatin （administered fluvastatin orally, 10 mg/kg body weight per day, n=-8）. Twelve weeks later, miniature cardiac catheter was inserted into the left ventricle to conduct hemodynamic examination. Then myocardium tissues were collected, collagen content was detected by picro-sirius red staining, real-time quantitative reverse transcription polymerase chain reaction （RT-PCR） was used to detect the mRNA expression of connective tissue growth factor （CTGF）, and Western blotting was used to detect the protein expression of CTGF. Rho activity was determined by pull-down assay. Results After 12 weeks, the left ventricular systolic pressure （LVSP） and maximum rate of left ventricular （LV） pressure rise and fall （＋dP/dt max and -dP/dt max） were significantly lower and left ventricular end diastolic pressure （LVEDP） was higher in the diabetic rats than those in the control rats （P 〈0.01）. Moreover, in LV myocardial tissue of diabetic rats the collagen content, fibronectin, mRNA and protein expression of CTGF and the activity of RhoA were all significantly increased compared with the control rats （P 〈0.01）. Administration of fluvastain obviously improved the cardiac function of diabetic rats, attenuated fibronectin expression, mRNA and protein expression of CTGF and the activity of RhoA in LV myocardium of diabetic rats. Conclusions Fluvastatin attenuates cardiac dysfunction
基金Supported by The European Union,Biomar Ca RE,No.HEALTH-2011-278913
文摘micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease mi RNAs have been proven to be reliable diagnostic biomarkers for different disease entities. In cardiac fibrosis(CF) and heart failure(HF) dysregulated circulating mi RNAs have been identified,indicating their promising applicability as diagnostic biomarkers. Some mi RNAs were successfully tested in risk stratification of HF implementing their potential use as prognostic biomarkers. In this respect mi RNAs might soon be implemented in diagnostic clinical routine. In the young field of mi RNA based research advances have been made in identifying mi RNAs as potential targets for the treatment of experimental CF and HF. Promising study results suggest their potential future application as therapeutic agents in treatment of cardiovascular disease. This article summarizes the current state of the various aspects of mi RNA research in the field of CF and HF with reduced ejection fraction as well as preserved ejection fraction. The review provides an overview of the application of circulating mi RNAs as biomarkers in CF and HF and current approaches to therapeutically utilize mi RNAs in this field of cardiovascular disease.
