目的探讨TRPC3基因多态性与原发性高血压患者左心室肥厚(LVH)的关系。方法305例原发性高血压患者根据左心室质量指数(LVMI)分为单纯高血压224例(对照组)和高血压合并LVH 81例(LVH组)。分析2组年龄、吸烟史等一般资料差异。留取外周血标...目的探讨TRPC3基因多态性与原发性高血压患者左心室肥厚(LVH)的关系。方法305例原发性高血压患者根据左心室质量指数(LVMI)分为单纯高血压224例(对照组)和高血压合并LVH 81例(LVH组)。分析2组年龄、吸烟史等一般资料差异。留取外周血标本,采用Sequenom MassARRAY®SNP检测技术对TRPC3基因单核苷酸多态性(SNP)位点Rs2292232、Rs4995894、Rs4292355进行基因分型。Logistic回归分析影响患者LVH的因素。结果(1)2组年龄、吸烟史、饮酒史、家族史、尿素、肌酐、空腹血糖、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、24 h平均舒张压(24 h DBP)差异无统计学意义(P>0.05),LVH组较对照组男性比例降低,而24 h平均收缩压(24 h SBP)、体质量指数(BMI)升高(P<0.05)。(2)2组Rs4995894及Rs4292355位点等位基因频率、基因型频率分布差异无统计学意义(P>0.05),TRPC3基因SNP位点Rs2292232基因型频率和等位基因频率分布差异有统计学意义(P<0.05),其中LVH组Rs2292232位点TT基因型频率较对照组更高(P<0.05)。(3)Logistic回归分析显示,女性(OR=0.332,95%CI:0.181~0.610)、较高24 h SBP(OR=1.035,95%CI:1.014~1.056)、TRPC3基因SNP Rs2292232 TT基因型(OR=2.105,95%CI:1.109~3.995)为原发性高血压患者发生LVH的独立危险因素(均P<0.05)。结论TRPC3基因Rs2292232位点SNP与高血压患者发生LVH有关,其中TT基因型患者更易发生LVH。展开更多
An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery.Our previous ...An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery.Our previous study has identified transient receptor potential channel 3(TRPC3)and TRPC6 as cation channels through which most of the damaging calcium enters,aggravates pathological changes in vivo and increases ischemia/reperfusion(I/R)injury in mice.This study aimed to verify the effects of TRPC3 inhibitor Pyr3 on myocardial I/R injury in mice.C57BL/6J wild-type male mice(8 to 12 weeks old)were anesthetized with 3.3%chloral hydrate.A murine I(30 min)/R(24 h)injury model was established by temporary occlusion of the left anterior descending(LAD)coronary artery.Pyr3 was administered at concentrations of 0,2.5,5,or 10 mg/kg via the right jugular vein 5 min before reperfusion.We observed that the selective TRPC3 inhibitor,10 mg/kg Pyr3,significantly decreased the infarct size of left ventricle,and reduced the myocardial cell apoptosis rate and inflammatory response in mice.In a conclusion,TRPC3 can function as a candidate target for I/R injury prevention,and Pyr3 may directly bind to TRPC3 channel protein,inhibit TRPC3 channel activity,and improve TRPC3-related myocardial I/R injury.Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases.展开更多
Recently studies found that TRPC3 and TRPC6 played an important role in cardiovascular disease. Hypertension, as a cardiovascular disease causing the highest morbidity and mortality, has close relationship with the ex...Recently studies found that TRPC3 and TRPC6 played an important role in cardiovascular disease. Hypertension, as a cardiovascular disease causing the highest morbidity and mortality, has close relationship with the expressions of TRPC3 and TRPC6. Unbalanced calcium homeostasis is the major factor of pathogenesis of hypertension. Changes of intracellular calcium concentration depend on calcium transmembrane transportation, intracellular calcium store releasing and other processes. TRPC3, TRPC6 molecules, as non-selective cation channels on the cell membranes, are involved in the processes. This review illustrated the functions of TRPC3 and TRPC6 on myocardial cells, smooth muscle cells and inflammatory cells in the development of hypertension, and the effects of drugs like sildenafil to provide a new way for the prevention and treatment of hypertension.展开更多
Transient receptor potential canonical subfamily member 3(TRPC3) is known to be important for neural development and the formation of neuronal networks. Here, we investigated the role of TRPC3 in undifferentiated mous...Transient receptor potential canonical subfamily member 3(TRPC3) is known to be important for neural development and the formation of neuronal networks. Here, we investigated the role of TRPC3 in undifferentiated mouse embryonic stem cells(mESCs) and during the differentiation of mESCs into neurons. CRISPR/Cas9-mediated knockout(KO) of TRPC3 induced apoptosis and the disruption of mitochondrial membrane potential both in undifferentiated mESCs and in those undergoing neural differentiation. In addition, TRPC3 KO impaired the pluripotency of mESCs. TRPC3 KO also dramatically repressed the neural differentiation of mESCs by inhibiting the expression of markers for neural progenitors, neurons, astrocytes and oligodendrocytes.Taken together, our new data demonstrate an important function of TRPC3 with regards to the survival, pluripotency and neural differentiation of mESCs.展开更多
文摘目的探讨TRPC3基因多态性与原发性高血压患者左心室肥厚(LVH)的关系。方法305例原发性高血压患者根据左心室质量指数(LVMI)分为单纯高血压224例(对照组)和高血压合并LVH 81例(LVH组)。分析2组年龄、吸烟史等一般资料差异。留取外周血标本,采用Sequenom MassARRAY®SNP检测技术对TRPC3基因单核苷酸多态性(SNP)位点Rs2292232、Rs4995894、Rs4292355进行基因分型。Logistic回归分析影响患者LVH的因素。结果(1)2组年龄、吸烟史、饮酒史、家族史、尿素、肌酐、空腹血糖、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、24 h平均舒张压(24 h DBP)差异无统计学意义(P>0.05),LVH组较对照组男性比例降低,而24 h平均收缩压(24 h SBP)、体质量指数(BMI)升高(P<0.05)。(2)2组Rs4995894及Rs4292355位点等位基因频率、基因型频率分布差异无统计学意义(P>0.05),TRPC3基因SNP位点Rs2292232基因型频率和等位基因频率分布差异有统计学意义(P<0.05),其中LVH组Rs2292232位点TT基因型频率较对照组更高(P<0.05)。(3)Logistic回归分析显示,女性(OR=0.332,95%CI:0.181~0.610)、较高24 h SBP(OR=1.035,95%CI:1.014~1.056)、TRPC3基因SNP Rs2292232 TT基因型(OR=2.105,95%CI:1.109~3.995)为原发性高血压患者发生LVH的独立危险因素(均P<0.05)。结论TRPC3基因Rs2292232位点SNP与高血压患者发生LVH有关,其中TT基因型患者更易发生LVH。
基金This study was supported by grants from the National Natural Science Foundation of China(No.81800266)Cultivating Project for Young Scholars at Hubei University of Medicine(No.2017QDJZR04 and No.2018QDJZR10).
文摘An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery.Our previous study has identified transient receptor potential channel 3(TRPC3)and TRPC6 as cation channels through which most of the damaging calcium enters,aggravates pathological changes in vivo and increases ischemia/reperfusion(I/R)injury in mice.This study aimed to verify the effects of TRPC3 inhibitor Pyr3 on myocardial I/R injury in mice.C57BL/6J wild-type male mice(8 to 12 weeks old)were anesthetized with 3.3%chloral hydrate.A murine I(30 min)/R(24 h)injury model was established by temporary occlusion of the left anterior descending(LAD)coronary artery.Pyr3 was administered at concentrations of 0,2.5,5,or 10 mg/kg via the right jugular vein 5 min before reperfusion.We observed that the selective TRPC3 inhibitor,10 mg/kg Pyr3,significantly decreased the infarct size of left ventricle,and reduced the myocardial cell apoptosis rate and inflammatory response in mice.In a conclusion,TRPC3 can function as a candidate target for I/R injury prevention,and Pyr3 may directly bind to TRPC3 channel protein,inhibit TRPC3 channel activity,and improve TRPC3-related myocardial I/R injury.Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases.
文摘Recently studies found that TRPC3 and TRPC6 played an important role in cardiovascular disease. Hypertension, as a cardiovascular disease causing the highest morbidity and mortality, has close relationship with the expressions of TRPC3 and TRPC6. Unbalanced calcium homeostasis is the major factor of pathogenesis of hypertension. Changes of intracellular calcium concentration depend on calcium transmembrane transportation, intracellular calcium store releasing and other processes. TRPC3, TRPC6 molecules, as non-selective cation channels on the cell membranes, are involved in the processes. This review illustrated the functions of TRPC3 and TRPC6 on myocardial cells, smooth muscle cells and inflammatory cells in the development of hypertension, and the effects of drugs like sildenafil to provide a new way for the prevention and treatment of hypertension.
基金supported by the Hong Kong Research Grants Council(RGC)General Research Fund awards(662113,16101714,16100115)the ANR/RGC joint research scheme award(AHKUST601/13)+1 种基金the Hong Kong Theme-based Research Scheme award(T13-706/11-1)the Hong Kong Innovation and Technology Commission(ITCPD/17-9)
文摘Transient receptor potential canonical subfamily member 3(TRPC3) is known to be important for neural development and the formation of neuronal networks. Here, we investigated the role of TRPC3 in undifferentiated mouse embryonic stem cells(mESCs) and during the differentiation of mESCs into neurons. CRISPR/Cas9-mediated knockout(KO) of TRPC3 induced apoptosis and the disruption of mitochondrial membrane potential both in undifferentiated mESCs and in those undergoing neural differentiation. In addition, TRPC3 KO impaired the pluripotency of mESCs. TRPC3 KO also dramatically repressed the neural differentiation of mESCs by inhibiting the expression of markers for neural progenitors, neurons, astrocytes and oligodendrocytes.Taken together, our new data demonstrate an important function of TRPC3 with regards to the survival, pluripotency and neural differentiation of mESCs.
