Diabetes alters vascular mechanotransduction: pressure-induced regulation of mitogen activated protein kinases in the rat inferior vena cava.
Diabetes alters vascular mechanotransduction: pressure-induced regulation of mitogen activated protein kinases in the rat inferior vena cava.
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DOI：
10.1186/1475-2840-5-18
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发表时间：
2006-09-08
影响因子：
9.3
通讯作者：
Blough ER
中科院分区：
文献类型：
--
作者：
Rice KM;Desai DH;Kakarla SK;Katta A;Preston DL;Wehner P;Blough ER
糖尿病是导致搭桥手术后静脉移植失败增加的重要危险因素。然而，该人群中血管磨损的细胞和分子机制(S)在很大程度上仍未被探索。最近的报道表明，移植静脉的病理重塑可能是通过机械诱导丝裂原活化蛋白激酶(MAPK)信号通路的激活和MAPK相关的caspase-3活性的诱导而实现的。根据这些发现，我们假设糖尿病可能与静脉对机械负荷改变的“感觉”和“反应”的改变有关。分离非糖尿病瘦大鼠(LNZ)和糖尿病肥胖大鼠(OSXZ)的下腔静脉(IVC)，在基础或加压条件下(120 Mm Hg)体外孵育。免疫印迹法检测蛋白表达、基础激活及加压激活MAPK通路和细胞凋亡相关信号的能力。免疫印迹分析显示，与非糖尿病大鼠相比，糖尿病大鼠静脉内皮细胞中细胞外信号调节激酶(ERK1/2)、p38和c-Jun NH2末端激酶(JNK)MAPKs的表达和激活存在差异。尤其是p38β-(52.3±11.8%；45.8±18.2%)、JNK1-(21.5±9.3%；19.4±11.6%)和JNK3-MAPK(16.8±3.3%；29.5±17.6%)在糖尿病下腔静脉中的表达和基础磷酸化水平显著升高(P<0.05)。下腔静脉腔内压力的急剧增加不能增加糖尿病肥胖Zucker大鼠ERK1-、JNK-2或任何p38-MAPK的磷酸化。下腔静脉负荷后，Caspase-3和Caspase-9的裂解分别增加了276.0±36.0%和85.8±25.1%(P<0.05)，但对OSXZ中的caspase-3和caspase-9的裂解无明显影响。Bax和Bcl2的表达在组间差异无统计学意义。而Akt、磷酸化Akt、PTEN、磷酸化PTEN和磷酸化Bad在糖尿病下腔静脉中的基础表达水平较高(P<；0.05)。这些数据表明，糖尿病与下腔静脉激活MAPK和细胞凋亡相关信号的能力显著改变有关。这些变化是否与糖尿病人群中出现的静脉移植物磨损增加有关，还需要进一步的研究。
Diabetes mellitus is an important risk factor for increased vein graft failure after bypass surgery. However, the cellular and molecular mechanism(s) underlying vessel attrition in this population remain largely unexplored. Recent reports have suggested that the pathological remodeling of vein grafts may be mediated by mechanically-induced activation of the mitogen activated protein kinase (MAPK) signaling pathways and the MAPK-related induction of caspase-3 activity. On the basis of these findings, we hypothesized that diabetes may be associated with alterations in how veins "sense" and "respond" to altered mechanical loading. Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and the diabetic obese (OSXZ) Zucker rats were isolated and incubated ex vivo under basal or pressurized conditions (120 mmHg). Protein expression, basal activation and the ability of increased pressure to activate MAPK pathways and apoptosis-related signaling was evaluated by immunoblot analysis. Immunoblot analyses revealed differential expression and activation of extracellular signal-regulated kinase (ERK1/2), p38 and c-Jun NH2-terminal kinase (JNK) MAPKs in the IVCs of diabetic rats as compared to non-diabetic rats. In particular, the expression and basal phosphorylation of p38β- (52.3 ± 11.8%; 45.8 ± 18.2%), JNK 1- (21.5 ± 9.3%; 19.4 ± 11.6%) and JNK3-MAPK (16.8 ± 3.3%; 29.5 ± 17.6%) were significantly higher (P < 0.05) in the diabetic vena cava. An acute increase in IVC intraluminal pressure failed to increase the phosphorylation of ERK1-, JNK-2, or any of the p38-MAPKs in the diabetic obese Zucker rats. Also, IVC loading in the LNZ led to a 276.0 ± 36.0% and 85.8 ± 25.1% (P < 0.05) increase in the cleavage of caspase-3 and caspase-9, respectively, with no effect on these molecules in the OSXZ. No differences were found in the regulation of Bax and Bcl-2 between groups. However, basal expression levels of Akt, phospho-Akt, PTEN, phospho-PTEN and phospho-Bad were higher in the diabetic venae cavae (P < 0.05). These data suggest that diabetes is associated with significant alteration in the ability of the vena cava to activate MAPK- and apoptosis-related signaling. Whether these changes are associated with the increased vein graft attrition seen in the diabetic population will require further investigation.
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影响因子：
37.8
作者：
Ho, FM;Liu, SH;Lin-Shiau, SY
通讯作者：
Lin-Shiau, SY
影响因子：
8.3
作者：
Kobayashi, T;Taguchi, K;Kamata, K
通讯作者：
Kamata, K
影响因子：
6.1
作者：
Campbell, CSG;Caperuto, LC;Carvalho, CRO
通讯作者：
Carvalho, CRO
影响因子：
12.4
作者：
Dietrich, N;Thastrup, J;Kallunki, T
通讯作者：
Kallunki, T
影响因子：
19.6
作者：
Glogowski, EA;Tsiani, E;Whiteside, C
通讯作者：
Whiteside, C