中国心血管病研究2024，Vol.22Issue(12) ：1125-1130.DOI:10.3969/j.issn.1672-5301.2024.12.013

半胱氨酸丰富跨膜成骨蛋白调控因子1-骨形态发生蛋白4信号通路对血管紧张素Ⅱ诱导的心室肌细胞肥大的调控作用研究

Study on the regulation effect of cysteine-rich transmembrane bone morphogenetic protein regulator 1-bone morphogenetic protein 4 on ventricular myocyte hypertrophy induced by angiotensin Ⅱ

李语 杨龙 何炯红 欧巧巧 杨英
中国心血管病研究2024，Vol.22Issue(12) ：1125-1130.DOI:10.3969/j.issn.1672-5301.2024.12.013
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半胱氨酸丰富跨膜成骨蛋白调控因子1-骨形态发生蛋白4信号通路对血管紧张素Ⅱ诱导的心室肌细胞肥大的调控作用研究

Study on the regulation effect of cysteine-rich transmembrane bone morphogenetic protein regulator 1-bone morphogenetic protein 4 on ventricular myocyte hypertrophy induced by angiotensin Ⅱ

李语 1杨龙 2何炯红 2欧巧巧 2杨英2
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作者信息

  • 1. 550025 贵州省贵阳市,贵州医科大学研究生院
  • 2. 贵州省人民医院心内科
  • 折叠

摘要

目的 探讨半胱氨酸丰富跨膜成骨蛋白调控因子1(Crim1)是否通过抑制骨形态发生蛋白4(BMP4)而调节血管紧张素Ⅱ(AngⅡ)诱导的心室肌细胞肥大.方法 分离1d龄SD大鼠乳鼠心室肌获心室肌细胞,按干预方式不同分九组:Ad-Null(腺病毒空载体)组、Ad-Null+AngⅡ、Ad-Null+AngⅡ+Nog(重组人头蛋白)组、Ad-Crim 1(Crim 1 基因重组腺病毒载体)组、Ad-Crim1+Ang Ⅱ 组、Ad-Crim1+Ang Ⅱ+Nog组、Ad-shCrim1(shRNA 干扰介导沉默 Crim1 基因重组腺病毒载体)组、Ad-shCrim 1+Ang Ⅱ 组和 Ad-shCrim 1+Ang Ⅱ+Nog组.实时荧光定量逆转录PCR检测β-肌球蛋白重链(β-MHC)和BMP4的mRNA表达.Western免疫印迹法检测全细胞提取蛋白BMP4的表达.细胞经结晶紫染色后通过Image J软件测量细胞表面积.结果 AngⅡ干预明显增加心室肌细胞β-MHC mRNA表达以及细胞面积,上调BMP4 mRNA/蛋白表达;Ad-Crim1和Nog干预明显抑制AngⅡ的上述效应.Ad-shCrim1干预沉默Crim1基因对心室肌细胞β-MHC mRNA表达,细胞面积及BMP4mRNA/蛋白表达与Ang Ⅱ干预效应相似,该效应为Nog干预明显抑制.结论 Crim1通过下调BMP4的表达而抑制Ang Ⅱ诱导的乳鼠心室肌细胞肥大.

Abstract

Objective To investigate whether cysteine rich transmembrane osteogenic protein regulatory factor 1(Crim1)regulates angiotensin Ⅱ(Ang Ⅱ)-induced ventricular myocyte hypertrophy by inhibiting bone morphogenetic protein 4(BMP4).Methods The ventricular myocytes from 1-day-old SD rats were isolated and divided into nine groups according to different intervention methods:Ad-Null(adenovirus empty vector)group,Ad-Null+Ang Ⅱ group,Ad-Null+Ang Ⅱ+Nog(recombinant human noggin)group,Ad-Crim1(recombinant adenovirus vector of Crim1 gene)group,Ad-Crim1+Ang Ⅱ group,Ad-Crim1+Ang Ⅱ+Nog group,Ad-shCrim1(shRNA interference mediated silencing of Crim1 gene recombination adenovirus vector)group,Ad-shCrim1+Ang Ⅱ group and Ad-shCrim1+Ang Ⅱ+Nog group.The mRNA expression of myosin heavy chain beta(β-MHC)and BMP4 was detected by RT-qPCR.The protein level of BMP4 in the whole-cell extracts was determined by Western blot analysis.The cells stained with crystal violet were measured for cell surface area using Image J software.Results AngⅡ intervention significantly increased β-MHC mRNA expression,BMP4 mRNA/protein expression and cell area of ventricular myocytes;the above effects of AngⅡ intervention were significantly inhibited by pre-using of Ad-Crim 1 and Nog.Crim1 gene of ventricular myocytes silenced by Ad-shCriml intervention leading to the similar effects of Ang Ⅱ intervention on β-MHC mRNA expression,BMP4 mRNA/protein expression and cell area,those were significantly inhibited by Nog intervention.Conclusions Crim1 inhibits Ang Ⅱ-induced hypertrophy of neonatal rat ventricular myocytes by decreasing BMP4 expression.

关键词

心肌肥大/半胱氨酸丰富跨膜成骨蛋白调控因子1/骨形态发生蛋白4/血管紧张素Ⅱ

Key words

Myocardial hypertrophy/Cysteine rich transmembrane osteogenic protein regulatory factor 1/Bone morphogenetic protein 4/Angiotensin Ⅱ

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出版年

2024
中国心血管病研究
中国医师协会，煤炭总医院

中国心血管病研究

CSTPCD
影响因子：0.878
ISSN：1672-5301
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