mRNA Expression Profile Changes in Angiotensin-Ⅱ-Induced Atrial Myocardial Fibrosis in Rats

QIN Qiuyu, LYU Xiangwei, HE Zifeng, C Liqin, LU Fengxia, LI Yuting, HUANG Yuli, MO Qi, XU Huaxin, LYU Fei

Abstract

 To study the differences between the mRNA expression profile in angiotensin Ⅱ (Ang Ⅱ)-induced fibrotic cardiomyocytes and that of normal cardiomyocytes and the relevant signaling pathways.   Methods  Six 8-week-old male Sprague-Dawley (SD) rats were randomly assigned to a control group and an Ang Ⅱ group, with 3 rats in each group. Rats in the control group were injected via caudal vein with 0.9% normal saline at 2 mg/kg per day, while rats in the Ang Ⅱ group were injected with Ang Ⅱ via caudal vein at 2 mg/kg per day. The medications were continuously administered in the two groups for 14 days. The degree of myocardial fibrosis was determined by Masson's Trichrome staining and the content of collagen Ⅰ was determined by immunohistochemistry. High throughput sequencing was performed to measure the mRNA expression of rat cardiomyocytes in the two groups and to screen for differentially-expressed mRNAs. The differentially-expressed mRNAs were analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.   Results  Compared with those of the control group, the degree of myocardial fibrosis and the content of collagen Ⅰ in Ang Ⅱ group were significantly higher (P<0.05). Through sequencing, 313 differentially-expressed mRNAs were identified, with 201 being up-regulated and 112 being down-regulated. Go and KEGG analyses showed that these differentially-expressed mRNA were involved in a variety of biological regulatory functions and pathways of myocardial fibrosis.   Conclusion  Ang Ⅱ can cause myocardial fibrosis in rats. There are significant differences in mRNA expression between fibrotic cardiomyocytes and normal cardiomyocytes. The differentially expressed mRNAs may play an important role in biological processes, including immune response, cell remodeling, and extracellular matrix deposition.


Keywords: Angiotensin ,  Myocardioal fibrosis, mRNA

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SOHNS C, MARROUCHE F N. Atrial fibrillation and cardiac fibrosis. Eur Heart J,2020,41(10): 1123–1131. doi: 10.1093/eurheartj/ehz786.

XU J J, LI R J, ZHANG Z H, et al. Loganin inhibits angiotensin Ⅱ-induced cardiac hypertrophy through the JAK2/STAT3 and NF-κB signaling pathways. Front Pharmacol,2021,12: 678886. doi: 10.3389/fphar.2021.678886.

CHEN Y M, WANG L, HUANG S X, et al. Lutein attenuates angiotensin Ⅱ-induced cardiac remodeling by inhibiting AP-1/IL-11 signaling. Redox Biol,2021,44: 102020. doi: 10.1016/j.redox.2021.102020.

GE Z W, CHEN Y M, WANG B, et al. MFGE8 attenuates Ang-Ⅱ-induced atrial fibrosis and vulnerability to atrial fibrillation through inhibition of TGF-β1/Smad2/3 pathway. J Mol Cell Cardiol,2020,139: 164–175. doi: 10.1016/j.yjmcc.2020.01.001.

LV W K, ZHANG L, CHENG X C, et al. Apelin inhibits angiotensin Ⅱ-induced atrial fibrosis and atrial fibrillation via TGF-β1/Smad2/α-SMA pathway. Front Physiol,2020,11: 583570. doi: 10.3389/fphys.2020. 583570.

HU J, ZHANG J J, LI L, et al. PU.1 inhibition attenuates atrial fibrosis and atrial fibrillation vulnerability induced by angiotensin-Ⅱ by reducing TGF-β1/Smads pathway activation. J Cell Mol Med,2021,25(14): 6746–6759. doi: 10.1111/jcmm.16678.

COWLING T R, KUPSKY D, KAHN M A, et al. Mechanisms of cardiac collagen deposition in experimental models and human disease. Transl Res,2019,209: 138–155. doi: 10.1016/j.trsl.2019.03.004.

HARIKRISHNAN V, TITUS S A, COWLING T R, et al. Collagen receptor cross-talk determines α-smooth muscle actin-dependent collagen gene expression in angiotensin Ⅱ–stimulated cardiac fibroblasts. J Biol Chem,2019,294(51): 19723–19739. doi: 10.1074/jbc.RA119.009744.

JIANG H M, WANG H X, YANG H, et al. Role for granulocyte colony stimulating factor in angiotensin Ⅱ-induced neutrophil recruitment and cardiac fibrosis in mice. Am J Hypertens,2013,26(10): 1224–1233. doi: 10.1093/ajh/hpt095.

JITMANA R, RAKSAPHARM S, KIJTAWORNRAT A, et al. Role of cardiac mast cells in exercise training-mediated cardiac remodeling in angiotensin Ⅱ-infused ovariectomized rats. Life Sci,2019,219: 209–218. doi: 10.1016/j.lfs.2019.01.018.

YAO Y J, YANG M, LIU D S W, et al. Immune remodeling and atrial fibrillation. Front Physiol,2022,13: 927221. doi: 10.3389/fphys.2022. 927221.

DZIAŁO E, RUDNIK M, KONING I R, et al. WNT3a and WNT5a transported by exosomes activate WNT signaling pathways in human cardiac fibroblasts. Int J Mol Sci,2019,20(6): 1436. doi: 10.3390/ijms20061436.

DZIAŁO E, CZEPIEL M, TKACZ K, et al. WNT/β-Catenin signaling promotes TGF-β-mediated activation of human cardiac fibroblasts by enhancing IL-11 production. Int J Mol Sci,2021,22(18): 10072. doi: 10. 3390/ijms221810072.

XU L, CUI W H, ZHOU W C, et al. Activation of Wnt/β-catenin signalling is required for TGF-β/Smad2/3 signalling during myofibroblast proliferation. J Cell Mol Med,2017,21(8): 1545–1554. doi: 10.1111/jcmm. 13085.

ZHAI C G, XU Y Y, TIE Y Y, et al. DKK3 overexpression attenuates cardiac hypertrophy and fibrosis in an angiotensin-perfused animal model by regulating the ADAM17/ACE2 and GSK-3β/β-catenin pathways. J Mol Cell Cardiol,2018,114: 243–252. doi: 10.1016/j.yjmcc. 2017.11.018.

LV X W, LI J Y, HU Y S, et al. Overexpression of miR-27b-3p targeting Wnt3a regulates the signaling pathway of Wnt/β-Catenin and attenuates atrial fibrosis in rats with atrial fibrillation. Oxid Med Cell Longev,2019, 2019: 5703764. doi: 10.1155/2019/5703764.

SMALL M E, BROOKS C A. Cut the YAP: limiting fibrosis in pathologic cardiac remodeling. JACC Basic Transl Sci,2020,5(9): 946–948. doi: 10. 1016/j.jacbts.2020.08.004.

FRANCISCO J, ZHANG Y, JEONG I J, et al. Blockade of fibroblast YAP attenuates cardiac fibrosis and dysfunction through MRTF-A inhibition. JACC Basic Transl Sci,2020,5(9): 931–945. doi: 10.1016/j. jacbts.2020.07.009.

MIA M M, CIBI D M, GHANI S, et al. Loss of Yap/Taz in cardiac fibroblasts attenuates adverse remodelling and improves cardiac function. Cardiovasc Res,2021,2021: cvab205. doi: 10.1093/cvr/cvab205.

PAN D F, ZHOU Y F, XIAO S J, et al. Identification of differentially expressed genes and pathways in human atrial fibrillation by bioinformatics analysis. Int J Gen Med,2022,15: 103–114. doi: 10.2147/IJGM.S334122.


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