αV integrins are necessary for eutrophic inward remodeling of small arteries in hypertension
αV integrins are necessary for eutrophic inward remodeling of small arteries in hypertension
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DOI：
10.1161/01.hyp.0000198428.45132.02
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发表时间：
2006-02-01
期刊：
影响因子：
8.3
通讯作者：
Heagerty, AM
中科院分区：
文献类型：
--
作者：
Heerkens, EHJ;Shaw, L;Heagerty, AM
人类原发性高血压的特征是小动脉的富营养化重塑，几乎没有证据表明肥大。同样，年轻的高血压TGR（mRen 2）27动物的血管也经历了类似的结构改变。随着血压升高，检查了在营养重建过程中TGR（mRen 2）27阻力动脉中整合素的作用。最初，鉴定了8种α和3种β整联蛋白，并使用RT-PCR研究了表达水平。随着压力增加和重塑进展，整合素表达谱显示，只有α V显著升高。同时，我们证实了TGR（mRen 2）27大鼠动脉中整合素α V蛋白水平升高，并使用免疫荧光定位于培养基。α 1和β 3，而不是β 5整合素亚基与整合素α V共沉淀，并参与富营养化重塑过程。给药α V β 3肽拮抗剂可消除重塑，但可促进生长，表明肥厚是对高血压诱导的室壁应力增加的反应。我们已经确定，唯一上调的整合素，整合素α V β 3的α V亚基，在TGR（mRen 2）27大鼠阻力动脉的高血压重塑过程中具有至关重要的作用。在高血压重塑过程中，特异性α V β 3-细胞外基质相互作用的功能可能允许血管平滑肌细胞长度自动调节，其包括迁移过程，以在长时间收缩状态后维持狭窄的管腔。
Human essential hypertension is characterized by eutrophic remodeling of small arteries, with little evidence of hypertrophy. Likewise, vessels of young hypertensive TGR(mRen2) 27 animals have undergone similar structural alterations. The role of integrins in resistance arteries of TGR( mRen2) 27 during the eutrophic-remodeling process was examined as blood pressure rose. Initially, 8 alpha and 3 beta integrins were identified and levels of expression investigated using RT-PCR. As pressure increased and remodeling advanced, integrin expression profiles revealed that only alpha V was significantly raised. In conjunction, we confirmed elevated integrin alpha V protein levels in TGR( mRen2) 27 rat arteries and localization to the media using immunofluorescence. alpha 1 and beta 3, but not beta 5 integrin subunits were coprecipitated with integrin alpha V and are implicated in the eutrophic remodeling process. Administration of a peptide antagonist of alpha V beta 3 abolished remodeling but enhanced growth, indicating that hypertrophy supervened as a response to hypertension-induced increases in wall stress. We have established that the only upregulated integrin, the alpha V subunit of integrin alpha V beta 3, has a crucial role in the hypertensive remodeling process of TGR( mRen2) 27 rat resistance arteries. During hypertensive remodeling, functions of specific alpha V beta 3-extracellular matrix interactions are likely to allow vascular smooth muscle cell - length autoregulation, which includes a migratory process, to maintain a narrowed lumen after a prolonged constricted state.