Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12.
Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12.
复制标题
血管功能障碍先于与大鼠 12 号染色体上的血压基因座相关的高血压。
DOI：
10.1152/ajpheart.00464.2014
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Lazar,Jozef
中科院分区：
文献类型：
--
作者：
Prisco,SashaZ;Priestley,JessicaRC;Weinberg,BrianD;Prisco,AnthonyR;Hoffman,MatthewJ;Jacob,HowardJ;Flister,MichaelJ;Lombard,JulianH;Lazar,Jozef
We previously isolated a 6.1-Mb region of SS/Mcwi (Dahl salt-sensitive) rat chromosome 12 (13.4–19.5 Mb) that significantly elevated blood pressure (BP) (Δ+34 mmHg,P< 0.001) compared with the SS-12BNconsomic control. In the present study, we examined the role of vascular dysfunction and remodeling in hypertension risk associated with the 6.1-Mb (13.4–19.5 Mb) locus on rat chromosome 12 by reducing dietary salt, which lowered BP levels so that there were no substantial differences in BP between strains. Consequently, any observed differences in the vasculature were considered BP-independent. We also reduced the candidate region from 6.1 Mb with 133 genes to 2 Mb with 23 genes by congenic mapping. Both the 2 Mb and 6.1 Mb congenic intervals were associated with hypercontractility and decreased elasticity of resistance vasculature prior to elevations of BP, suggesting that the vascular remodeling and dysfunction likely contribute to the pathogenesis of hypertension in these congenic models. Of the 23 genes within the narrowed congenic interval, 12 were differentially expressed between the resistance vasculature of the 2 Mb congenic and SS-12BNconsomic strains. Among these,Grifinwas consistently upregulated 2.7 ± 0.6-fold (P< 0.05) and 2.0 ± 0.3-fold (P< 0.01), andChst12was consistently downregulated −2.8 ± 0.3-fold (P< 0.01) and −4.4 ± 0.4-fold (P< 0.00001) in the 2 Mb congenic compared with SS-12BNconsomic under normotensive and hypertensive conditions, respectively. A syntenic region on human chromosome 7 has also been associated with BP regulation, suggesting that identification of the genetic mechanism(s) underlying cardiovascular phenotypes in this congenic strain will likely be translated to a better understanding of human hypertension.
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影响因子：
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作者：
Peralta, Carmen A.;Adeney, Kathryn L.;Kestenbaum, Bryan R.
通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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血管反应性的遗传决定因素
影响因子：
5.6
作者：
D. Henrion;J. Bénessiano;M. Iglarz;I. Philip;B. I. Lévy
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使用 SSLP 对大鼠进行全基因组扫描。
DOI：
--
发表时间：
2005
期刊：
Methods in Molecular Medicine
影响因子：
--
作者：
Carol Moreno;K. Kennedy;Jaime Wendt Andrae;H. Jacob
通讯作者：
H. Jacob