MicroRNA-27b-3p Down-regulates FGF1 and Aggravates Pathological Cardiac Remodelling

Overview

Journal Cardiovasc Res

Specialty Cardiology & Vascular Diseases

Date 2021 Aug 6

PMID 34358309

Citations 27

Authors

Guoqi Li

Yihui Shao

Hong Chang Guo

Ying Zhi

Bokang Qiao

Ke Ma

Jie Du

Yong Qiang Lai

Yulin Li

Affiliations

Soon will be listed here.

Abstract

Aims: The heart undergoes pathological remodelling under increased stress and neuronal imbalance. MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. This study aimed to explore the function of endogenous microRNA-27b-3p (miR-27b-3p) in pathological cardiac remodelling.

Methods And Results: miR-27b-3p expression was elevated in the heart of a transverse aortic constriction (TAC)-induced cardiac hypertrophy mouse model. miR-27b-knockout mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation induced by two independent pathological cardiac hypertrophy models, TAC and Angiotensin II (Ang II) perfusion. Transcriptome sequencing analysis revealed that miR-27b deletion significantly down-regulated TAC-induced cardiac hypertrophy, fibrosis, and inflammatory genes. We identified fibroblast growth factor 1 (FGF1) as a miR-27b-3p target gene in the heart which was up-regulated in miR-27b-null mice. We found that both recombinant FGF1 (rFGF1) and inhibition of miR-27b-3p enhanced mitochondrial oxidative phosphorylation (OXPHOS) and inhibited cardiomyocyte hypertrophy. Importantly, rFGF1 administration inhibited cardiac hypertrophy and fibrosis in TAC- or Ang II-induced models and enhanced OXPHOS by activating PGC1α/β.

Conclusions: Our study demonstrated that miR-27b-3p induces pathological cardiac remodelling and suggests that inhibition of endogenous miR-27b-3p or administration of FGF1 might have the potential to suppress cardiac remodelling in a clinical setting.

Citing Articles

Biochanin A Mitigates Pressure Overload-Induced Cardiac Hypertrophy Through Modulation of the NF-κB/Cbl-b/NLRP3 Signaling Axis.

Ba L, Wu N, Feng X, Wang R, Zhao Z, Wang R Cardiovasc Drugs Ther. 2025; .

PMID: 39976876 DOI: 10.1007/s10557-025-07677-2.

Myocardial ferroptosis may exacerbate the progression of atrial fibrillation through isolevuglandins.

Yue Z, Li X, Shi Z, Li X Eur J Med Res. 2025; 30(1):93.

PMID: 39940048 PMC: 11823066. DOI: 10.1186/s40001-025-02302-2.

Integrated analysis of ATAC-seq and RNA-seq reveals ADSCP2 regulates oxidative phosphorylation pathway in hypertrophic scar fibroblasts.

Li Q, Quan Z, Chen L, Yin Y, Chen X, Li J PeerJ. 2025; 13:e18902.

PMID: 39902331 PMC: 11789661. DOI: 10.7717/peerj.18902.

Deciphering Oxidative Stress in Cardiovascular Disease Progression: A Blueprint for Mechanistic Understanding and Therapeutic Innovation.

Zhang Z, Guo J Antioxidants (Basel). 2025; 14(1).

PMID: 39857372 PMC: 11759168. DOI: 10.3390/antiox14010038.

Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.

Mondejar-Parreno G, Moreno-Manuel A, Ruiz-Robles J, Jalife J Cell Discov. 2025; 11(1):3.

PMID: 39788950 PMC: 11717978. DOI: 10.1038/s41421-024-00738-0.

References

Arany Z, Novikov M, Chin S, Ma Y, Rosenzweig A, Spiegelman B . Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-gamma coactivator 1alpha. Proc Natl Acad Sci U S A. 2006; 103(26):10086-91. PMC: 1502510. DOI: 10.1073/pnas.0603615103. View

Palmen M, Daemen M, De Windt L, Willems J, Dassen W, Heeneman S . Fibroblast growth factor-1 improves cardiac functional recovery and enhances cell survival after ischemia and reperfusion: a fibroblast growth factor receptor, protein kinase C, and tyrosine kinase-dependent mechanism. J Am Coll Cardiol. 2004; 44(5):1113-23. DOI: 10.1016/j.jacc.2004.05.067. View

Kumar V, Santhosh Kumar T, Kartha C . Mitochondrial membrane transporters and metabolic switch in heart failure. Heart Fail Rev. 2018; 24(2):255-267. DOI: 10.1007/s10741-018-9756-2. View

Small E, Olson E . Pervasive roles of microRNAs in cardiovascular biology. Nature. 2011; 469(7330):336-42. PMC: 3073349. DOI: 10.1038/nature09783. View

Seok H, Chen J, Kataoka M, Huang Z, Ding J, Yan J . Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy. Circ Res. 2014; 114(10):1585-95. PMC: 4033580. DOI: 10.1161/CIRCRESAHA.114.303784. View

Gurha P, Abreu-Goodger C, Wang T, Ramirez M, Drumond A, van Dongen S . Targeted deletion of microRNA-22 promotes stress-induced cardiac dilation and contractile dysfunction. Circulation. 2012; 125(22):2751-61. PMC: 3503489. DOI: 10.1161/CIRCULATIONAHA.111.044354. View

Liu Y, Afzal J, Vakrou S, Greenland G, Talbot Jr C, Hebl V . Differences in microRNA-29 and Pro-fibrotic Gene Expression in Mouse and Human Hypertrophic Cardiomyopathy. Front Cardiovasc Med. 2020; 6:170. PMC: 6928121. DOI: 10.3389/fcvm.2019.00170. View

Zhai M, Liu Z, Zhang B, Jing L, Li B, Li K . Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating PGC-1β: In vivo and in vitro studies. J Pineal Res. 2017; 63(3). DOI: 10.1111/jpi.12433. View

Song S, Ito K, Ala U, Kats L, Webster K, Sun S . The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell. 2013; 13(1):87-101. PMC: 3767186. DOI: 10.1016/j.stem.2013.06.003. View

10.

Yu J, Lv Y, Di W, Liu J, Kong X, Sheng Y . MiR-27b-3p Regulation in Browning of Human Visceral Adipose Related to Central Obesity. Obesity (Silver Spring). 2017; 26(2):387-396. DOI: 10.1002/oby.22104. View

11.

Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O . Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab. 2005; 1(4):259-71. DOI: 10.1016/j.cmet.2005.03.002. View

12.

Heggermont W, Papageorgiou A, Quaegebeur A, Deckx S, Carai P, Verhesen W . Inhibition of MicroRNA-146a and Overexpression of Its Target Dihydrolipoyl Succinyltransferase Protect Against Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction. Circulation. 2017; 136(8):747-761. DOI: 10.1161/CIRCULATIONAHA.116.024171. View

13.

Itoh N, Ornitz D . Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease. J Biochem. 2010; 149(2):121-30. PMC: 3106964. DOI: 10.1093/jb/mvq121. View

14.

Pearson M, Mungovan S, Smart N . Effect of aerobic and resistance training on inflammatory markers in heart failure patients: systematic review and meta-analysis. Heart Fail Rev. 2018; 23(2):209-223. DOI: 10.1007/s10741-018-9677-0. View

15.

Caglayan E, Stauber B, Collins A, Lyon C, Yin F, Liu J . Differential roles of cardiomyocyte and macrophage peroxisome proliferator-activated receptor gamma in cardiac fibrosis. Diabetes. 2008; 57(9):2470-9. PMC: 2518499. DOI: 10.2337/db07-0924. View

16.

Goncalves L . Fibroblast growth factor-mediated angiogenesis for the treatment of ischemia. Lessons learned from experimental models and early human experience. Rev Port Cardiol. 1998; 17 Suppl 2:II11-20. View

17.

Fon Tacer K, L Bookout A, Ding X, Kurosu H, John G, Wang L . Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol. 2010; 24(10):2050-64. PMC: 2954642. DOI: 10.1210/me.2010-0142. View

18.

Facundo H, Brainard R, Caldas F, Brito Lucas A . Mitochondria and Cardiac Hypertrophy. Adv Exp Med Biol. 2017; 982:203-226. DOI: 10.1007/978-3-319-55330-6_11. View

19.

Beenken A, Mohammadi M . The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 2009; 8(3):235-53. PMC: 3684054. DOI: 10.1038/nrd2792. View

20.

Yang S, Wang K, Qian C, Song Z, Pu P, Zhang A . A predicted miR-27a-mediated network identifies a signature of glioma. Oncol Rep. 2012; 28(4):1249-56. DOI: 10.3892/or.2012.1955. View