From Dissection of Fibrotic Pathways to Assessment of Drug Interactions to Reduce Cardiac Fibrosis and Heart Failure

Overview

Journal Curr Res Pharmacol Drug Discov

Date 2021 Dec 15

PMID 34909666

Citations 7

Authors

Gloria Garoffolo

Maurizio Pesce

Affiliations

Soon will be listed here.

Abstract

Cardiac fibrosis is characterized by extracellular matrix deposition in the cardiac interstitium, and this contributes to cardiac contractile dysfunction and progression of heart failure. The main players involved in this process are the cardiac fibroblasts, which, in the presence of pro-inflammatory/pro-fibrotic stimuli, undergo a complete transformation acquiring a more proliferative, a pro-inflammatory and a secretory phenotype. This review discusses the cellular effectors and molecular pathways implicated in the pathogenesis of cardiac fibrosis and suggests potential strategies to monitor the effects of specific drugs designed to slow down the progression of this disease by specifically targeting the fibroblasts.

Citing Articles

Exogenous ECM in an environmentally-mediated model for cardiac fibrosis.

Pachter N, Allen K, Hookway T bioRxiv. 2024; .

PMID: 39229021 PMC: 11370619. DOI: 10.1101/2024.08.20.608840.

Contractile effects of stimulation of D-dopamine receptors in the isolated human atrium.

Gergs U, Pham T, Rayo Abella L, Hesse C, Grundig P, Dhein S Naunyn Schmiedebergs Arch Pharmacol. 2024; 398(2):1497-1508.

PMID: 39102031 PMC: 11825631. DOI: 10.1007/s00210-024-03340-z.

YAP/TAZ: Molecular pathway and disease therapy.

Wei Y, Lee Zhi Hui V, Chen Y, Han R, Han X, Guo Y MedComm (2020). 2023; 4(4):e340.

PMID: 37576865 PMC: 10412783. DOI: 10.1002/mco2.340.

Cells and Materials for Cardiac Repair and Regeneration.

Alhejailan R, Garoffolo G, Raveendran V, Pesce M J Clin Med. 2023; 12(10).

PMID: 37240504 PMC: 10219302. DOI: 10.3390/jcm12103398.

Role of Dopamine in the Heart in Health and Disease.

Neumann J, Hofmann B, Dhein S, Gergs U Int J Mol Sci. 2023; 24(5).

PMID: 36902474 PMC: 10003060. DOI: 10.3390/ijms24055042.

References

Basser P, Mattiello J, Lebihan D . MR diffusion tensor spectroscopy and imaging. Biophys J. 1994; 66(1):259-67. PMC: 1275686. DOI: 10.1016/S0006-3495(94)80775-1. View

Dong Z, Guo J, Xing X, Zhang X, Du Y, Lu Q . RGD modified and PEGylated lipid nanoparticles loaded with puerarin: Formulation, characterization and protective effects on acute myocardial ischemia model. Biomed Pharmacother. 2017; 89:297-304. DOI: 10.1016/j.biopha.2017.02.029. View

Massie B, Carson P, McMurray J, Komajda M, McKelvie R, Zile M . Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008; 359(23):2456-67. DOI: 10.1056/NEJMoa0805450. View

Lim S, Cho D, Jeong H, Kang H, Kim M, Cho M . Adjuvant role of macrophages in stem cell-induced cardiac repair in rats. Exp Mol Med. 2018; 50(11):1-10. PMC: 6218450. DOI: 10.1038/s12276-018-0171-5. View

Annes J, Munger J, Rifkin D . Making sense of latent TGFbeta activation. J Cell Sci. 2002; 116(Pt 2):217-24. DOI: 10.1242/jcs.00229. View

Meng G, Wu F, Yang L, Zhu H, Gu J, He M . Synergistic attenuation of myocardial fibrosis in spontaneously hypertensive rats by joint treatment with benazepril and candesartan. J Cardiovasc Pharmacol. 2009; 54(1):16-24. DOI: 10.1097/FJC.0b013e3181a98b31. View

Francisco J, Zhang Y, Jeong J, Mizushima W, Ikeda S, Ivessa A . Blockade of Fibroblast YAP Attenuates Cardiac Fibrosis and Dysfunction Through MRTF-A Inhibition. JACC Basic Transl Sci. 2020; 5(9):931-945. PMC: 7524792. DOI: 10.1016/j.jacbts.2020.07.009. View

Schorb W, Booz G, Dostal D, Conrad K, Chang K, Baker K . Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts. Circ Res. 1993; 72(6):1245-54. DOI: 10.1161/01.res.72.6.1245. View

Derynck R, Zhang Y . Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003; 425(6958):577-84. DOI: 10.1038/nature02006. View

10.

Swynghedauw B . Molecular mechanisms of myocardial remodeling. Physiol Rev. 1999; 79(1):215-62. DOI: 10.1152/physrev.1999.79.1.215. View

11.

Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A . Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol. 2002; 159(6):1029-37. PMC: 2173981. DOI: 10.1083/jcb.200207165. View

12.

Brilla C, Matsubara L, Weber K . Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol. 1993; 25(5):563-75. DOI: 10.1006/jmcc.1993.1066. View

13.

Crabos M, Roth M, Hahn A, Erne P . Characterization of angiotensin II receptors in cultured adult rat cardiac fibroblasts. Coupling to signaling systems and gene expression. J Clin Invest. 1994; 93(6):2372-8. PMC: 294443. DOI: 10.1172/JCI117243. View

14.

Abbate A, Salloum F, Van Tassell B, Vecile E, Toldo S, Seropian I . Alterations in the interleukin-1/interleukin-1 receptor antagonist balance modulate cardiac remodeling following myocardial infarction in the mouse. PLoS One. 2011; 6(11):e27923. PMC: 3225370. DOI: 10.1371/journal.pone.0027923. View

15.

Herum K, Choppe J, Kumar A, Engler A, McCulloch A . Mechanical regulation of cardiac fibroblast profibrotic phenotypes. Mol Biol Cell. 2017; 28(14):1871-1882. PMC: 5541838. DOI: 10.1091/mbc.E17-01-0014. View

16.

Bakin A, Rinehart C, Tomlinson A, Arteaga C . p38 mitogen-activated protein kinase is required for TGFbeta-mediated fibroblastic transdifferentiation and cell migration. J Cell Sci. 2002; 115(Pt 15):3193-206. DOI: 10.1242/jcs.115.15.3193. View

17.

Levick S, Soto-Pantoja D, Bi J, Hundley W, Widiapradja A, Manteufel E . Doxorubicin-Induced Myocardial Fibrosis Involves the Neurokinin-1 Receptor and Direct Effects on Cardiac Fibroblasts. Heart Lung Circ. 2018; 28(10):1598-1605. PMC: 7901001. DOI: 10.1016/j.hlc.2018.08.003. View

18.

Teg Pipes G, Creemers E, Olson E . The myocardin family of transcriptional coactivators: versatile regulators of cell growth, migration, and myogenesis. Genes Dev. 2006; 20(12):1545-56. DOI: 10.1101/gad.1428006. View

19.

Bujak M, Frangogiannis N . The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovasc Res. 2006; 74(2):184-95. PMC: 1924687. DOI: 10.1016/j.cardiores.2006.10.002. View

20.

Deng B, Shen L, Wu Y, Shen Y, Ding X, Lu S . Delivery of alginate-chitosan hydrogel promotes endogenous repair and preserves cardiac function in rats with myocardial infarction. J Biomed Mater Res A. 2014; 103(3):907-18. DOI: 10.1002/jbm.a.35232. View