Atrial (ANP) and brain natriuretic peptide (BNP) expression after myocardial infarction in sheep: ANP is synthesized by fibroblasts infiltrating the infarct
Atrial (ANP) and brain natriuretic peptide (BNP) expression after myocardial infarction in sheep: ANP is synthesized by fibroblasts infiltrating the infarct
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DOI：
10.1210/en.141.12.4690
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发表时间：
2000-12-01
期刊：
影响因子：
4.8
通讯作者：
Richards, AM
中科院分区：
文献类型：
--
作者：
Cameron, VA;Rademaker, MT;Richards, AM
心肌梗死后，心钠肽（ANP）和脑钠肽（BNP）基因表达明显升高。用原位杂交法比较绵羊左冠状动脉结扎5周后ANP和BNP信使RNA （mRNA）的细胞分布和时间反应。结扎导致高度可重复的、跨壁的左心室梗死。结扎后7天梗死内出现ANP mRNA，而任何时间梗死内均未检测到BNP的表达。原位杂交和免疫细胞化学显示合成ANP的细胞为侵袭梗死灶的成纤维细胞。ANP表达的出现与这些细胞向肌成纤维细胞表型的转变一致。用转化生长因子- β (10 ng/ml)处理培养的心脏成纤维细胞，诱导α -平滑肌肌动蛋白的表达，这是向肌成纤维细胞转化的特征，并提高了培养基中的ANP浓度。在存活的左心室心肌中，ANP和BNP的表达随着结扎而增加，其中BNP mRNA在梗死侧缘的表达尤为强烈。左、右心房BNP mRNA水平在梗死后18小时内显著升高，而心房ANP mRNA水平在梗死后3天内下降。这是心肌成纤维细胞侵袭纤维化瘢痕时ANP表达和合成的首次报道，提示在修复性纤维化过程中，ANP可能参与调节成纤维细胞增殖。
Cardiac gene expression of atrial natriuretic peptide (ANP) and that of brain natriuretic peptide (BNP) are markedly elevated after myocardial infarction. The cellular distribution and temporal responses of ANP and BNP messenger RNA (mRNA) expression mere compared by in situ hybridization for 5 weeks after left coronary artery ligation in sheep. Ligation resulted in highly reproducible, transmural, left ventricular infarcts. Within the infarct, ANP mRNA appeared from 7 days after ligation, whereas BNP expression was undetectable in the infarct at any time. The cells synthesizing ANP were shown by in situ hybridization and immunocytochemistry to be fibroblasts invading the infarct. The appearance of ANP expression coincided with the transition of these cells to the myofibroblast phenotype. Treatment of cultured cardiac fibroblasts with transforming growth factor-beta (10 ng/ml) induced the expression of alpha -smooth muscle actin, characteristic of the transformation to myofibroblasts, and raised ANP concentrations in the medium. In the surviving myocardium of the left ventricle, ANP and BNP expression increased in response to ligation, BNP mRNA was particularly strong at the lateral margins of the infarct. In both left, and right atria, levels of BNP mRNA increased markedly over the first 18 h, whereas levels of atrial ANP mRNA decreased over 3 days after infarction. This is the first report of ANP expression and synthesis by cardiac fibroblasts invading the fibrotic scar, suggesting that ANP may be involved in regulating fibroblast proliferation during reparative fibrosis.