目的:了解北京社区人群内源性促红细胞生成素(erythropoietin,EPO)的相关因素及其与10年心血管疾病发病风险的关系。方法:数据来源于2011年12月至2012年4月北京大学第一医院动脉粥样硬化队列的基线资料,采用多因素线性回归模型分析内源...目的:了解北京社区人群内源性促红细胞生成素(erythropoietin,EPO)的相关因素及其与10年心血管疾病发病风险的关系。方法:数据来源于2011年12月至2012年4月北京大学第一医院动脉粥样硬化队列的基线资料,采用多因素线性回归模型分析内源性EPO的相关因素,应用中国动脉粥样硬化性心血管疾病风险预测(prediction for atherosclerotic cardiovascular disease risk in China,China-PAR)模型计算研究对象10年心血管疾病发病风险,以5%、10%为切点定义低、中、高风险分层。结果:共纳入4013名基线无心脑血管疾病、无贫血、肾功能未见异常的研究对象,女性占比62.2%(2496人),平均年龄(55.9±8.2)岁,平均EPO水平为12.8(9.3~17.4)IU/L。10年心血管疾病风险高危者占比25.1%(998人)。多因素回归结果显示,血红蛋白(β=-0.05,95%CI:-0.07~-0.04)和肾小球滤过率≥90 mL/(min·1.73 m^(2))(β=-0.05,95%CI:-0.07~-0.04)与EPO水平呈显著负相关,高血压(β=0.08,95%CI:0.05~0.12)和肥胖(β=0.14,95%CI:0.09~0.18)与内源性EPO水平升高显著相关。10年心血管疾病风险与内源性EPO水平呈显著正相关(β=0.07,95%CI:0.05~0.09),中危者以及高危者内源性EPO水平均显著高于与低危者(P均<0.05)。结论:北京市社区居民内源性EPO水平与血红蛋白、肾功能、肥胖及高血压呈显著相关性,10年心血管疾病风险中、高危者内源性EPO水平显著高于低危者,可能是心血管疾病风险标志物。展开更多
SUMMARY Since the 1980 s nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), the endogenous gas molecules produced from metabolic pathway, have been realized as signal molecules to be involved in the r...SUMMARY Since the 1980 s nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), the endogenous gas molecules produced from metabolic pathway, have been realized as signal molecules to be involved in the regulation of body homeostasis and to play important roles under physiological and pathophysiological conditions. The researches on these endogenous gas signal molecules opened a new avenue in life science. To explore the new member of gasotransmitter family, other endogenous gas molecules which have been regarded as metabolic waste up to date, and their biological regulatory effects have been paid close attention to in the current fields of life science and medicine. Sulfur dioxide (SO2) can be produced endogenously from normal metabolism of sulfur-containing amino acids. L-cysteine is oxidized via cysteine dioxygenase to L-cysteinesulfinate, and the latter can proceed through transamination by glutamate oxaloacetate transaminase (GOT) to β-sulfinylpyruvate which decomposes spontaneously to pyruvate and SO2. In mammals, activated neutrophils by oxidative stress can convert H2S to sulfite through a reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent process. The authors detected endogenous production of SO2 in all cardiovascular tissues, including in heart, aorta, pulmonary artery, mesenteric artery, renal artery, tail artery and the plasma SO2 content. As the key enzyme producing SO2, GOT mRNA in cardiovascular system was detected and found to be located enrichedly in endothelial cells and vascular smooth muscle cells near the endothelial layer.When the normal rats were treated with hydroxamate(HDX), a GOT inhibitor, at a dose of 3.7 mg/kg body weight, the blood pressure (BP) went high markedly, the ratio of wall thickness to lumen radius was increased by 18.34%, and smooth muscle cell proliferation was enhanced. The plasma SO2 level in the rats injected with 125 μmol/kg body weight SO2 donor was increased to 721.98±30.11 μmol/L at the end of 30 seconds, while the blood pressure was decreased to the lowest point 65.0± 4.9 mm Hg at the end of 1 minute. The above results showed that endogenous SO2 might be involved in the maintenance of blood pressure and normal vascular structure. In spontaneous hypertensive rat (SHR) animal model, exogenous supplement of SO2 donor decreased the BP, the media cross-sectional area, and pressure of the media and the ratio of wall thickness to lumen radius in the SHR. Moreover, the proliferative index of aortic smooth muscle cells was decreased in the SHR treated with SO2 donor compared with that in SHR. The above data showed that SO2 could prevent the aortic structural remodeling by inhibiting the proliferation of aortic smooth muscle cells.The authors observed the direct vasorelaxant effects of SO2 on the aortic ring pre-treated with norepinephrin (NE). SO2 donor at a concentration of 25—100 μmol/L relaxed the aortic ring temporarily and slightly, but SO2 donor at a concentration of 1—12 mmol/L induced relaxation of the ring in a concentration-dependent manner. Administration with nicardipine, an L-type calcium channel blocker other than glibenclamide, an ATP sensitive potassium channel (KATP channel) blocker or removal of vascular endothelium could decrease the SO2-induced vasorelaxation. In hypoxic pulmonary hypertension animal model, SO2 donor decreased the mean pulmonary artery pressure and the systolic pulmonary artery pressure (P<0.01), respectively as compared with hypoxic group, and alleviated obviously the hypoxic pulmonary vascular structural remodeling. The percentage of muscularized arteries of small pulmonary vessels was significantly decreased in hypoxia+SO2 donor-treated rats compared with that of hypoxic rats (P<0.01), while the percentage of non-muscularized vessels was obviously higher in hypoxia with SO2 donor-treated rats than that of hypoxic rats (P<0.01). Similarly, SO2 obviously decreased relative media area and relative media thickness of small muscularized pulmonary arteries in hypoxic rats (P<0.01). The above data showed that SO2 might play an important role in development of hypoxic pulmonary hypertension.Perfusion with SO2 donor (10-6—10-3 mol/L) to the isolated rat heart obviously inhibited the left ventricular peak rate of contraction ( + LV dp/ dtmax) , peak rate of relaxation ( -LV dp/ dtmax) and difference of left ventricular pressure ( ΔLVP) in a concentration dependent manner. Nicardipine, an L-type calcium channel blocker, could partly antagonize the inhibitory effect of SO2 on the heart function. In a word, SO2 could be endogenously generated in cardiovascular tissues and exert important cardiovascular effects such as vasorelaxant effect and negative inotropic effects. Moreover, SO2 might play considerable roles in the regulation of systemic circulatory pressure, pulmonary circulatory pressure and vascular structural remodeling in the pathogenesis of hypertension and hypoxic pulmonary hypertension. On the basis of the above findings, we presumed that endogenous SO2 might be a novel cardiovascular functional regulatory gasotransmitter. More studies on the significance of endogenous SO2 in cardiovascular system under physiological and pathophysiological conditions need to be investigated.展开更多
Midkine (MK),a newly discovered heparin-binding growth factor,promotes growth,survival,and migration in various cells. Meanwhile,MK stimulates statistically significant forms in new arterioles and capillaries,causes v...Midkine (MK),a newly discovered heparin-binding growth factor,promotes growth,survival,and migration in various cells. Meanwhile,MK stimulates statistically significant forms in new arterioles and capillaries,causes vascular remodeling,prevents ischemia myocardial cells from injury via inhibiting apoptosis. MK also regulates the level of blood-fat. In general,MK plays key roles in cardiovascular diseases.展开更多
文摘目的:了解北京社区人群内源性促红细胞生成素(erythropoietin,EPO)的相关因素及其与10年心血管疾病发病风险的关系。方法:数据来源于2011年12月至2012年4月北京大学第一医院动脉粥样硬化队列的基线资料,采用多因素线性回归模型分析内源性EPO的相关因素,应用中国动脉粥样硬化性心血管疾病风险预测(prediction for atherosclerotic cardiovascular disease risk in China,China-PAR)模型计算研究对象10年心血管疾病发病风险,以5%、10%为切点定义低、中、高风险分层。结果:共纳入4013名基线无心脑血管疾病、无贫血、肾功能未见异常的研究对象,女性占比62.2%(2496人),平均年龄(55.9±8.2)岁,平均EPO水平为12.8(9.3~17.4)IU/L。10年心血管疾病风险高危者占比25.1%(998人)。多因素回归结果显示,血红蛋白(β=-0.05,95%CI:-0.07~-0.04)和肾小球滤过率≥90 mL/(min·1.73 m^(2))(β=-0.05,95%CI:-0.07~-0.04)与EPO水平呈显著负相关,高血压(β=0.08,95%CI:0.05~0.12)和肥胖(β=0.14,95%CI:0.09~0.18)与内源性EPO水平升高显著相关。10年心血管疾病风险与内源性EPO水平呈显著正相关(β=0.07,95%CI:0.05~0.09),中危者以及高危者内源性EPO水平均显著高于与低危者(P均<0.05)。结论:北京市社区居民内源性EPO水平与血红蛋白、肾功能、肥胖及高血压呈显著相关性,10年心血管疾病风险中、高危者内源性EPO水平显著高于低危者,可能是心血管疾病风险标志物。
文摘SUMMARY Since the 1980 s nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), the endogenous gas molecules produced from metabolic pathway, have been realized as signal molecules to be involved in the regulation of body homeostasis and to play important roles under physiological and pathophysiological conditions. The researches on these endogenous gas signal molecules opened a new avenue in life science. To explore the new member of gasotransmitter family, other endogenous gas molecules which have been regarded as metabolic waste up to date, and their biological regulatory effects have been paid close attention to in the current fields of life science and medicine. Sulfur dioxide (SO2) can be produced endogenously from normal metabolism of sulfur-containing amino acids. L-cysteine is oxidized via cysteine dioxygenase to L-cysteinesulfinate, and the latter can proceed through transamination by glutamate oxaloacetate transaminase (GOT) to β-sulfinylpyruvate which decomposes spontaneously to pyruvate and SO2. In mammals, activated neutrophils by oxidative stress can convert H2S to sulfite through a reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent process. The authors detected endogenous production of SO2 in all cardiovascular tissues, including in heart, aorta, pulmonary artery, mesenteric artery, renal artery, tail artery and the plasma SO2 content. As the key enzyme producing SO2, GOT mRNA in cardiovascular system was detected and found to be located enrichedly in endothelial cells and vascular smooth muscle cells near the endothelial layer.When the normal rats were treated with hydroxamate(HDX), a GOT inhibitor, at a dose of 3.7 mg/kg body weight, the blood pressure (BP) went high markedly, the ratio of wall thickness to lumen radius was increased by 18.34%, and smooth muscle cell proliferation was enhanced. The plasma SO2 level in the rats injected with 125 μmol/kg body weight SO2 donor was increased to 721.98±30.11 μmol/L at the end of 30 seconds, while the blood pressure was decreased to the lowest point 65.0± 4.9 mm Hg at the end of 1 minute. The above results showed that endogenous SO2 might be involved in the maintenance of blood pressure and normal vascular structure. In spontaneous hypertensive rat (SHR) animal model, exogenous supplement of SO2 donor decreased the BP, the media cross-sectional area, and pressure of the media and the ratio of wall thickness to lumen radius in the SHR. Moreover, the proliferative index of aortic smooth muscle cells was decreased in the SHR treated with SO2 donor compared with that in SHR. The above data showed that SO2 could prevent the aortic structural remodeling by inhibiting the proliferation of aortic smooth muscle cells.The authors observed the direct vasorelaxant effects of SO2 on the aortic ring pre-treated with norepinephrin (NE). SO2 donor at a concentration of 25—100 μmol/L relaxed the aortic ring temporarily and slightly, but SO2 donor at a concentration of 1—12 mmol/L induced relaxation of the ring in a concentration-dependent manner. Administration with nicardipine, an L-type calcium channel blocker other than glibenclamide, an ATP sensitive potassium channel (KATP channel) blocker or removal of vascular endothelium could decrease the SO2-induced vasorelaxation. In hypoxic pulmonary hypertension animal model, SO2 donor decreased the mean pulmonary artery pressure and the systolic pulmonary artery pressure (P<0.01), respectively as compared with hypoxic group, and alleviated obviously the hypoxic pulmonary vascular structural remodeling. The percentage of muscularized arteries of small pulmonary vessels was significantly decreased in hypoxia+SO2 donor-treated rats compared with that of hypoxic rats (P<0.01), while the percentage of non-muscularized vessels was obviously higher in hypoxia with SO2 donor-treated rats than that of hypoxic rats (P<0.01). Similarly, SO2 obviously decreased relative media area and relative media thickness of small muscularized pulmonary arteries in hypoxic rats (P<0.01). The above data showed that SO2 might play an important role in development of hypoxic pulmonary hypertension.Perfusion with SO2 donor (10-6—10-3 mol/L) to the isolated rat heart obviously inhibited the left ventricular peak rate of contraction ( + LV dp/ dtmax) , peak rate of relaxation ( -LV dp/ dtmax) and difference of left ventricular pressure ( ΔLVP) in a concentration dependent manner. Nicardipine, an L-type calcium channel blocker, could partly antagonize the inhibitory effect of SO2 on the heart function. In a word, SO2 could be endogenously generated in cardiovascular tissues and exert important cardiovascular effects such as vasorelaxant effect and negative inotropic effects. Moreover, SO2 might play considerable roles in the regulation of systemic circulatory pressure, pulmonary circulatory pressure and vascular structural remodeling in the pathogenesis of hypertension and hypoxic pulmonary hypertension. On the basis of the above findings, we presumed that endogenous SO2 might be a novel cardiovascular functional regulatory gasotransmitter. More studies on the significance of endogenous SO2 in cardiovascular system under physiological and pathophysiological conditions need to be investigated.
文摘Midkine (MK),a newly discovered heparin-binding growth factor,promotes growth,survival,and migration in various cells. Meanwhile,MK stimulates statistically significant forms in new arterioles and capillaries,causes vascular remodeling,prevents ischemia myocardial cells from injury via inhibiting apoptosis. MK also regulates the level of blood-fat. In general,MK plays key roles in cardiovascular diseases.
