Cigarette smoke-induced left ventricular remodelling is associated with activation of mitogen-activated protein kinases.

Cigarette smoke-induced left ventricular remodelling is associated with activation of mitogen-activated protein kinases.
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香烟烟雾引起的左心室重构与丝裂原激活蛋白激酶的激活有关。

DOI:
10.1016/j.ejheart.2008.08.009
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发表时间:
2008-11
影响因子:
18.2
通讯作者:
Piano, Mariann R.
Piano, Mariann R.
中科院分区:
医学1区
文献类型:
--
作者:
Gu, Lianzhi;Pandey, Vikas;Geenen, David L.;Chowdhury, Shamim A. K.;Piano, Mariann R.

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研究香烟烟雾(CS)暴露对丝裂原活化蛋白激酶(MAPK)(细胞外信号调节激酶[ERK 1/2]、p38激酶[p38]和c-Jun氨基末端蛋白激酶[JNK])表达/活化、去甲肾上腺素(NE)水平以及心肌结构和功能的影响。将大鼠随机分为两组:CS暴露组(n = 10)或室内空气(CON)组(n = 12)。5周后,动物进行超声心动图与脉冲波多普勒血流测量。取出心脏进行显微镜检查和Western印迹分析。CS暴露与尿NE水平显著增加和心室尺寸(mm)增大相关(CON =左心室舒张末期尺寸[LVEDD] 7.99 ± 0.10,LV收缩末期尺寸[LVESD] 4.55 ± 0.20,CS = LVEDD 8.3 ± 0.10,LVESD 5.3 ± 0.09,p = 0.026,p = 0.003)。与CON组相比,CS暴露组中也存在收缩功能障碍的证据(缩短分数%,CON = 43 ± 2,CS = 36 ± .09,p = 0.010)。与对照组(0.464 ± 0.008,0.459 ± 0.050)相比,CS组磷酸化p38/总p38(0.975 ± 0.05)和磷酸化ERK 1/2/总ERK 1/2(1.919 ± 0.050)显著增加。各组间JNK水平无显著差异。NE水平升高和MAPK激活与CS相关的左心室重构相关。
To determine the effects of cigarette smoke (CS) exposure on the expression/activation of mitogen-activated protein kinases (MAPKs) (extracellular signal-regulated kinase [ERK1/2], p38-kinase [p38] and c-Jun NH2–terminal protein kinase [JNK]), norepinephrine (NE) levels and myocardial structure and function. Rats were randomised to two groups: CS–exposed (n = 10) or room air (CON) (n = 12). After 5 weeks, the animals underwent echocardiography with pulse-wave Doppler flow measurements. Hearts were removed for microscopy and Western blot analysis. CS exposure was associated with significant increases in NE urinary levels and larger ventricular dimensions (mm) (CON = left ventricular end diastolic dimension [LVEDD] 7.99 ± 0.10, LV end systolic dimension [LVESD] 4.55 ± 0.20, CS = LVEDD 8.3 ± 0.10, LVESD 5.3 ± 0.09, p = 0.026, p = 0.003). There was also evidence of systolic dysfunction in the CS-exposed group compared to the CON group (fractional shortening %, CON = 43 ± 2, CS = 36 ± .09, p = 0.010). In CS-exposed hearts, significant increases in phosphorylated p38/total p38 (0.975 ± 0.05) and phosphorylated ERK1/2/totalERK1/2 (1.919 ± 0.050) were found compared to CON hearts (0.464 ± 0.008, 0.459 ± 0.050, respectively). No significant differences were found in JNK levels between the groups. Increased NE levels and MAPK activation are associated with CS-related left ventricular remodelling.
DOI: 10.1002/j.1550-8528.1999.tb00393.x
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期刊: OBESITY RESEARCH
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