Myocardial osteopontin expression coincides with the development of heart failure
Myocardial osteopontin expression coincides with the development of heart failure
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DOI：
10.1161/01.hyp.33.2.663
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发表时间：
1999-02-01
期刊：
影响因子：
8.3
通讯作者：
Colucci, WS
中科院分区：
文献类型：
--
作者：
Singh, K;Sirokman, G;Colucci, WS
为了鉴定在从代偿性肥厚向心力衰竭转变过程中差异表达的基因，通过差异显示逆转录-聚合酶链反应比较了自发性高血压大鼠（SBR）心力衰竭（SHR-F）、年龄匹配的SHR代偿性肥厚（SHR-NF）和血压正常的Wistar-Kyoto大鼠（WKY）心肌mRNA。在SHR-F中差异表达的转录本的表征产生了与细胞外基质蛋白骨桥蛋白同源的cDNA。北方分析显示，在WKY和SHR-NF的左心室心肌中骨桥蛋白mRNA水平较低，而在SHR-F中骨桥蛋白mRNA水平显著升高（约10倍）。原位杂交显示，在心肌从WKY和SHR-NF，只有很少的骨桥蛋白mRNA，主要是在小动脉细胞。在SHR-F中，原位杂交显示骨桥蛋白mRNA的表达丰富，主要在间质和血管周围空间的非肌细胞中。在SHR-F组的心肌中壁区域观察到类似的骨桥蛋白结果。与SHR的结果一致，骨桥蛋白mRNA在压力超负荷肥大的非衰竭结扎大鼠左心室心肌中最低限度地增加（约1.9倍），但在失败的结扎大鼠中显著增加（约8倍）。在SHR衰竭发作之前或之后开始用卡托普利治疗，降低了左心室骨桥蛋白mRNA水平的增加。因此，骨桥蛋白的表达显着增加，在心脏符合心力衰竭的发展，在SHR-F的骨桥蛋白的来源主要是非肌细胞，其诱导抑制血管紧张素转换酶抑制剂，提示血管紧张素II的作用。鉴于骨桥蛋白的已知生物活性，包括细胞粘附和诱导型一氧化氮合酶基因表达的调节，这些数据表明，它可能在心力衰竭的病理生理学中发挥作用。
To identify genes that are differentially expressed during the transition from compensated hypertrophy to failure, myocardial mRNA from spontaneously hypertensive rats (SBR) with heart failure (SHR-F) was compared with that from age-matched SHR with compensated hypertrophy (SHR-NF) and normotensive Wistar-Kyoto rats (WKY) by differential display reverse transcriptase-polymerase chain reaction. Characterization of a transcript differentially expressed in SHR-F yielded a cDNA with homology to the extracellular matrix protein osteopontin. Northern analysis showed low levels of osteopontin mRNA in left ventricular myocardium from WKY and SHR-NF but a markedly increased (approximate to 10-fold) level in SHR-F. In myocardium from WKY and SHR-NF, in situ hybridization showed only scant osteopontin mRNA, primarily in arteriolar cells. In SHR-F, in situ hybridization revealed abundant expression of osteopontin mRNA, primarily in nonmyocytes in the interstitial and perivascular space. Similar findings for osteopontin protein were observed in the midwall region of myocardium from the SHR-F group. Consistent with the findings in SHR, osteopontin mRNA was minimally increased (approximate to 1.9-fold) in left ventricular myocardium from nonfailing aortic-banded rats with pressure-overload hypertrophy but was markedly increased (approximate to 8-fold) in banded rats with failure. Treatment with captopril starting before or after the onset of failure in the SHR reduced the increase in left ventricular osteopontin mRNA levels. Thus, osteopontin expression is markedly increased in the heart coincident with the development of heart failure, The source of osteopontin in SHR-F is primarily nonmyocytes, and its induction is inhibited by an angiotensin-converting enzyme inhibitor, suggesting a role for angiotensin II. Given the known biological activities of osteopontin, including cell adhesion and regulation of inducible nitric oxide synthase gene expression, these data suggest that it could play a role in the pathophysiology of heart failure.