Comprehensive gene expression profiling reveals synergistic functional networks in cerebral vessels after hypertension or hypercholesterolemia.
Comprehensive gene expression profiling reveals synergistic functional networks in cerebral vessels after hypertension or hypercholesterolemia.
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DOI：
10.1371/journal.pone.0068335
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wong PT
中科院分区：
文献类型：
--
作者：
Ong WY;Ng MP;Loke SY;Jin S;Wu YJ;Tanaka K;Wong PT
脑动脉粥样硬化性狭窄或颅内大动脉疾病（ICLAD）是中风的主要原因，特别是在亚洲人，西班牙人和非洲人中，但对风险血管的基因表达变化知之甚少。本研究比较了新西兰白色家兔大脑中动脉（MCA）的综合基因表达谱，这些家兔暴露于两种卒中风险因素，即高血压和/或高胆固醇血症，采用2-肾-1-夹方法或饮食补充胆固醇。高血压兔大脑中动脉微阵列和免疫抑制通路分析显示，在含有节点分子的网络中，UBC（ubiquitin）、P38 MAPK、ERK、NF κ B、SERPINB 2、MMP 1和APP（amyloid precursor protein）基因表达上调，MAPK、ERK 1/2、Akt、26 s蛋白酶体、组蛋白H3和UBC相关基因表达下调。高胆固醇血症兔的MCA显示出差异表达的基因，这些基因与高血压兔几乎相同的节点分子相关联，尽管这两种情况之间的“共同基因”百分比相对较低（21%和7%）。上调的共同基因与UBC、SERPINB 2、TNF、HNF 4A（hepatocyte nuclear factor 4A）和APP相关，下调的基因与UBC相关。在主动脉中证实了增加的HNF 4A信息和蛋白。总之，这些发现揭示了受高血压或高胆固醇血症影响的脑血管中类似的节点分子和基因通路，这可能是ICLAD发病机制中风险因素协同作用的基础。
Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD) is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA) of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin), P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein); and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of ‘common genes’ (21 and 7%) between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A) and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD.
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DOI：
10.1016/j.jstrokecerebrovasdis.2009.01.010
发表时间：
2009-11-01
影响因子：
2.5
作者：
De Silva, Deidre Anne;Woon, Fung-Peng;Wong, Meng-Cheong
通讯作者：
Wong, Meng-Cheong
影响因子：
2.5
作者：
AKIYAMA, H;IKEDA, K;MCGEER, PL
通讯作者：
MCGEER, PL
影响因子：
2.9
作者：
Brown, Aliza T.;Skinner, Robert D.;Flores, Rene;Hennings, Leah;Borrelli, Michael J.;Lowery, John;Culp, William C.
通讯作者：
Culp, William C.
影响因子：
37.8
作者：
Chen, CH;Jiang, T;Yang, CY
通讯作者：
Yang, CY
影响因子：
64.8
作者：
Boyden, Lynn M.;Choi, Murim;Choate, Keith A.;Nelson-Williams, Carol J.;Farhi, Anita;Toka, Hakan R.;Tikhonova, Irina R.;Bjornson, Robert;Mane, Shrikant M.;Colussi, Giacomo;Lebel, Marcel;Gordon, Richard D.;Semmekrot, Ben A.;Poujol, Alain;Valimaki, Matti J.;De Ferrari, Maria E.;Sanjad, Sami A.;Gutkin, Michael;Karet, Fiona E.;Tucci, Joseph R.;Stockigt, Jim R.;Keppler-Noreuil, Kim M.;Porter, Craig C.;Anand, Sudhir K.;Whiteford, Margo L.;Davis, Ira D.;Dewar, Stephanie B.;Bettinelli, Alberto;Fadrowski, Jeffrey J.;Belsha, Craig W.;Hunley, Tracy E.;Nelson, Raoul D.;Trachtman, Howard;Cole, Trevor R. P.;Pinsk, Maury;Bockenhauer, Detlef;Shenoy, Mohan;Vaidyanathan, Priya;Foreman, John W.;Rasoulpour, Majid;Thameem, Farook;Al-Shahrouri, Hania Z.;Radhakrishnan, Jai;Gharavi, Ali G.;Goilav, Beatrice;Lifton, Richard P.
通讯作者：
Lifton, Richard P.