Objective: Heart failure(HF), a worldwide health condition, is the result of many cardiovascular diseases.The traditional Chinese medicine(TCM) Xiaoyu Jiangzhi capsule(XYC) has long been in use in China to treat hyper...Objective: Heart failure(HF), a worldwide health condition, is the result of many cardiovascular diseases.The traditional Chinese medicine(TCM) Xiaoyu Jiangzhi capsule(XYC) has long been in use in China to treat hyperlipidemia and inhibit platelet aggregation. This study explores the effects of XYC on heart failure(HF) and its detailed mechanisms.Methods: Isoproterenol(ISO, 30 mg/kg) was injected intraperitoneally for 7 days to copy a HF model of 10-12 weeks old, 20-30 g male mice. We then compared the CON(control) group, ISO(HF model)group, MET(metoprolol) group, and XYC group. Cardiac systolic function and left wall thickness were evaluated by echocardiograph. Using western blot analysis, we detected the proteins of calmodulin dependent protein kinase Ⅱ(Ca MKII) and sarco/endoplasmic reticulum Ca^(2+)-ATPase(Serca). Furthermore, ts A201 cells were cultured and the human CaV1.2 calcium channel current(hCaV1.2) were detected by patch clamp experiments.Results: XYC reduced HF, inhibiting the protein expression of Ca MKII, but Serca did not change significantly. Moreover, XYC inhibited the peak amplitude of the hCaV1.2 current, depolarizing shifted the activation curve 27.6 mV, and shifted the inactivation curve toward a positive potential 17.6 mV. The fraction recovered from inaction was reduced in XYC group compared with that in CON group.Conclusion: XYC could inhibit ISO-induced HF by reducing the Ca^(2+)/Ca MKII signaling pathway in mice.展开更多
BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and...BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.展开更多
基金supported by the National Natural Science Foundation of Guangdong (2020A1515010777)the Fund of Chinese Medicine Bureau of Guangdong Province (20201142)。
文摘Objective: Heart failure(HF), a worldwide health condition, is the result of many cardiovascular diseases.The traditional Chinese medicine(TCM) Xiaoyu Jiangzhi capsule(XYC) has long been in use in China to treat hyperlipidemia and inhibit platelet aggregation. This study explores the effects of XYC on heart failure(HF) and its detailed mechanisms.Methods: Isoproterenol(ISO, 30 mg/kg) was injected intraperitoneally for 7 days to copy a HF model of 10-12 weeks old, 20-30 g male mice. We then compared the CON(control) group, ISO(HF model)group, MET(metoprolol) group, and XYC group. Cardiac systolic function and left wall thickness were evaluated by echocardiograph. Using western blot analysis, we detected the proteins of calmodulin dependent protein kinase Ⅱ(Ca MKII) and sarco/endoplasmic reticulum Ca^(2+)-ATPase(Serca). Furthermore, ts A201 cells were cultured and the human CaV1.2 calcium channel current(hCaV1.2) were detected by patch clamp experiments.Results: XYC reduced HF, inhibiting the protein expression of Ca MKII, but Serca did not change significantly. Moreover, XYC inhibited the peak amplitude of the hCaV1.2 current, depolarizing shifted the activation curve 27.6 mV, and shifted the inactivation curve toward a positive potential 17.6 mV. The fraction recovered from inaction was reduced in XYC group compared with that in CON group.Conclusion: XYC could inhibit ISO-induced HF by reducing the Ca^(2+)/Ca MKII signaling pathway in mice.
基金supported by a grant from Surface Project of Natural Science Foundation of Fujian Province(2008J0075)
文摘BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.
