Summary： Abnormal enhanced transmural dispersion of repolarization （TDR） plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes （TDP） which can be induced in ...Summary： Abnormal enhanced transmural dispersion of repolarization （TDR） plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes （TDP） which can be induced in long-QT （LQT） syndrome. Taking advantage of an in vitro rabbit model of LQT2, we de- tected the effects of KN-93, a CaM-dependent kinase （CaMK） II inhibitor on repolarization heteroge- neity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypo- kalemic, hypomagnesaemic Tyrode＇s solution. At a basic length （BCL） of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave （Tp-e） were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 （0.5μmol/L） could inhibit EAD, R-on-T extrasys- tole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demon- strated KN-93, a CaMK II inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.展开更多
Abnormal proliferation and migration of vascular smooth muscle cells （VSMCs） are the major cause of in-stent restenosis （ISR）. Intervention proliferation and migration of VSMCs is an im- portant strategy for antir...Abnormal proliferation and migration of vascular smooth muscle cells （VSMCs） are the major cause of in-stent restenosis （ISR）. Intervention proliferation and migration of VSMCs is an im- portant strategy for antirestenotic therapy. Roscovitine, a second-generation cyclin-dependent kinase in- hibitor, can inhibit cell cycle of multiple cell types. We studied the effects of roscovitine on cell cycle distribution, proliferation and migration of VSMCs in vitro by flow cytometry, BrdU incorporation and wound healing assay, respectively. Our results showed that roscovitine increased the proportion of Go/G1 phase cells after 12 h （69.57±3.65 vs. 92.50±1.68, P=0.000）, 24 h （80.87±2.24 vs. 90.25±0.79, P=0.000） and 48 h （88.08±3.86 vs. 88.87±2.43, P=-0.427） as compared with control group. Roscovifine inhibited proliferation and migration of VSMCs in a concentration-dependent way. With the increase of concen- tration, roscovitine showed increased capacity for growth and migration inhibition. Roscovitine （30 μmol/L） led to an almost complete VSMCs growth and migration arrest. Combined with its low toxicity and selective inhibition to ISR-VSMCs, roscovitine may be a potential drug in the treatment of vascular stenosis diseases and particularly useful in the prevention and treatment of ISR.展开更多
基金supported by Natural Science Foundation of Hubei Province,China(No.2008CDB163)
文摘Summary： Abnormal enhanced transmural dispersion of repolarization （TDR） plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes （TDP） which can be induced in long-QT （LQT） syndrome. Taking advantage of an in vitro rabbit model of LQT2, we de- tected the effects of KN-93, a CaM-dependent kinase （CaMK） II inhibitor on repolarization heteroge- neity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypo- kalemic, hypomagnesaemic Tyrode＇s solution. At a basic length （BCL） of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave （Tp-e） were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 （0.5μmol/L） could inhibit EAD, R-on-T extrasys- tole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demon- strated KN-93, a CaMK II inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.
基金supported by grants from the National Natural Science Foundation of China(Nos.30870641 and 81030021)the National Basic Research of China "973" Program(No.2011CB504403)
文摘Abnormal proliferation and migration of vascular smooth muscle cells （VSMCs） are the major cause of in-stent restenosis （ISR）. Intervention proliferation and migration of VSMCs is an im- portant strategy for antirestenotic therapy. Roscovitine, a second-generation cyclin-dependent kinase in- hibitor, can inhibit cell cycle of multiple cell types. We studied the effects of roscovitine on cell cycle distribution, proliferation and migration of VSMCs in vitro by flow cytometry, BrdU incorporation and wound healing assay, respectively. Our results showed that roscovitine increased the proportion of Go/G1 phase cells after 12 h （69.57±3.65 vs. 92.50±1.68, P=0.000）, 24 h （80.87±2.24 vs. 90.25±0.79, P=0.000） and 48 h （88.08±3.86 vs. 88.87±2.43, P=-0.427） as compared with control group. Roscovifine inhibited proliferation and migration of VSMCs in a concentration-dependent way. With the increase of concen- tration, roscovitine showed increased capacity for growth and migration inhibition. Roscovitine （30 μmol/L） led to an almost complete VSMCs growth and migration arrest. Combined with its low toxicity and selective inhibition to ISR-VSMCs, roscovitine may be a potential drug in the treatment of vascular stenosis diseases and particularly useful in the prevention and treatment of ISR.
