A newly developed angiotensin II type 1 receptor antagonist, CS866, promotes regression of cardiac hypertrophy by reducing integrin β1 expression
A newly developed angiotensin II type 1 receptor antagonist, CS866, promotes regression of cardiac hypertrophy by reducing integrin β1 expression
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DOI：
10.1291/hypres.26.737
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发表时间：
2003-09-01
影响因子：
5.4
通讯作者：
Kitabatake, A
中科院分区：
文献类型：
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作者：
Jia, N;Okamoto, H;Kitabatake, A
先前的研究表明，整合素在体外将细胞外基质与心肌细胞的肥厚反应途径联系起来。为了研究整合素β(1)与体内心脏肥厚之间的直接关系，我们研究了新开发的血管紧张素II型1 （AT(1)）阻滞剂CS866 （ARB， 10 mg/kg/天）、血管紧张素转换酶抑制剂替莫april （ACEI， 10 mg/kg/天）或两者对6 - 12周岁卒中易发自发性高血压大鼠（SHRSP）肥厚心脏中整合素β(1)的调节作用。ARB、ACEI和联合治疗可显著降低收缩压。然而，与ACEL治疗相比，ARB治疗或联合治疗的SHRSP心肌肥厚的减少更大。多重逆转录-聚合酶链反应显示，未治疗的SHRSP中心房利钠因子、AT(1)受体和整合素β(1)的mRNA表达明显高于正常血压的Wistar-Kyoto大鼠（WKY）。ARB、ACEI或联合治疗可显著降低SHRSP中ANP、AT(1)受体和整合素β(1)的mRNA水平。治疗后的SHRSP中ANP、AT(1)受体和整合素β (1) mRNA表达降低与血压降低有关；ARB和联合治疗比ACEI产生更大的表达下降。以上结果提示，CS866对心肌细胞肥厚具有有益作用，AT(1)受体的下调和整合素β(1)的抑制参与了体内压力性心肌肥厚的消退。整合素β(1)与AT(1)受体的表达有显著相关性。我们的研究结果还表明，血管紧张素II可能通过AT(1)受体调节肌细胞的整合素表达。
Previous studies have demonstrated that integrins link the extracellular matrix to the hypertrophic response pathway of cardiac myocytes in vitro. To examine the direct relation between integrin beta(1) and cardiac hypertrophy in vivo, we studied the effects of a newly developed angiotensin II type 1 (AT(1)) blocker, CS866 (ARB; 10 mg/kg/day), an angiotensin-converting enzyme inhibitor, temocapril (ACEI, 10 mg/kg/day), or both on modulation of integrin beta(1) in the hypertrophied hearts of stroke-prone spontaneously hypertensive rats (SHRSP) 6 to 12 weeks of age. Treatments with ARB, ACEI, and combination therapy significantly reduced systolic blood pressure. However, the reduction in cardiac hypertrophy was greater in SHRSP treated with ARB or combination therapy than in those treated with ACEL Multiplex reverse transcription-polymerase chain reaction revealed significantly higher mRNA expression of atrial natriuretic factor, AT(1) receptor, and integrin beta(1) in untreated SHRSP than in normotensive Wistar-Kyoto rats (WKY). The mRNA levels of ANP, AT(1) receptor, and integrin beta(1) in SHRSP were significantly decreased by treatment with ARB, ACEI, or combination therapy. Decreased mRNA expression of ANP, AT(1) receptor, and integrin beta(1) in the treated SHRSP was associated with reductions in blood pressure; ARB and combination therapy produced greater decreases in expression than did ACEI. These observations suggest that CS866 has a beneficial effect on myocyte hypertrophy and that down-regulation of AT(1) receptor and suppression of integrin beta(1) participate in the regression of pressure-induced cardiac hypertrophy in vivo. The correlation between the expression of integrin beta(1) and AT(1) receptor was significant. Our results also suggest that integrin expression by myocytes might be modulated by angiotensin II via AT(1) receptor.