The Role of TGFβ1 and LRG1 in Cardiac Remodelling and Heart Failure

Overview

Journal Biophys Rev

Publisher Springer

Specialty Biophysics

Date 2017 May 17

PMID 28509980

Citations 29

Authors

Weihua Song

Xiaomeng Wang

Affiliations

Soon will be listed here.

Abstract

Heart failure is a life-threatening condition that carries a considerable emotional and socio-economic burden. As a result of the global increase in the ageing population, sedentary life-style, increased prevalence of risk factors, and improved survival from cardiovascular events, the incidence of heart failure will continue to rise. Despite the advances in current cardiovascular therapies, many patients are not suitable for or may not benefit from conventional treatments. Thus, more effective therapies are required. Transforming growth factor (TGF) β family of cytokines is involved in heart development and dys-regulated TGFβ signalling is commonly associated with fibrosis, aberrant angiogenesis and accelerated progression into heart failure. Therefore, a potential therapeutic pathway is to modulate TGFβ signalling; however, broad blockage of TGFβ signalling may cause unwanted side effects due to its pivotal role in tissue homeostasis. We found that leucine-rich α-2 glycoprotein 1 (LRG1) promotes blood vessel formation via regulating the context-dependent endothelial TGFβ signalling. This review will focus on the interaction between LRG1 and TGFβ signalling, their involvement in the pathogenesis of heart failure, and the potential for LRG1 to function as a novel therapeutic target.

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References

Schumacher B, Pecher P, von Specht B, Stegmann T . Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heart disease. Circulation. 1998; 97(7):645-50. DOI: 10.1161/01.cir.97.7.645. View

Rosengart T, Lee L, Patel S, Sanborn T, Parikh M, Bergman G . Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation. 1999; 100(5):468-74. DOI: 10.1161/01.cir.100.5.468. View

Henry T, Rocha-Singh K, Isner J, Kereiakes D, Giordano F, Simons M . Intracoronary administration of recombinant human vascular endothelial growth factor to patients with coronary artery disease. Am Heart J. 2001; 142(5):872-80. DOI: 10.1067/mhj.2001.118471. View

Lopez J, Edelman E, Stamler A, Hibberd M, Prasad P, Thomas K . Angiogenic potential of perivascularly delivered aFGF in a porcine model of chronic myocardial ischemia. Am J Physiol. 1998; 274(3):H930-6. DOI: 10.1152/ajpheart.1998.274.3.H930. View

Norgren L, Hiatt W, Dormandy J, Nehler M, Harris K, Fowkes F . Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007; 45 Suppl S:S5-67. DOI: 10.1016/j.jvs.2006.12.037. View

Kim I, Moon S, Kim S, Kim H, Koh Y, Koh G . Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin through nuclear factor-kappa B activation in endothelial cells. J Biol Chem. 2000; 276(10):7614-20. DOI: 10.1074/jbc.M009705200. View

Guergova-Kuras M, Kurucz I, Hempel W, Tardieu N, Kadas J, Malderez-Bloes C . Discovery of lung cancer biomarkers by profiling the plasma proteome with monoclonal antibody libraries. Mol Cell Proteomics. 2011; 10(12):M111.010298. PMC: 3237079. DOI: 10.1074/mcp.M111.010298. View

Unger E, Goncalves L, Epstein S, Chew E, Trapnell C, Cannon 3rd R . Effects of a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris. Am J Cardiol. 2000; 85(12):1414-9. DOI: 10.1016/s0002-9149(00)00787-6. View

Blaxall B, Spang R, Rockman H, Koch W . Differential myocardial gene expression in the development and rescue of murine heart failure. Physiol Genomics. 2003; 15(2):105-14. DOI: 10.1152/physiolgenomics.00087.2003. View

10.

Gopalakrishnan K, Morgan E, Yerga-Woolwine S, Farms P, Kumarasamy S, Kalinoski A . Augmented rififylin is a risk factor linked to aberrant cardiomyocyte function, short-QT interval and hypertension. Hypertension. 2011; 57(4):764-71. PMC: 3060303. DOI: 10.1161/HYPERTENSIONAHA.110.165803. View

11.

Ladd J, Busald T, Johnson M, Zhang Q, Pitteri S, Wang H . Increased plasma levels of the APC-interacting protein MAPRE1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women. Cancer Prev Res (Phila). 2012; 5(4):655-64. PMC: 3419141. DOI: 10.1158/1940-6207.CAPR-11-0412. View

12.

McMullen J, Shioi T, Zhang L, Tarnavski O, Sherwood M, Dorfman A . Deletion of ribosomal S6 kinases does not attenuate pathological, physiological, or insulin-like growth factor 1 receptor-phosphoinositide 3-kinase-induced cardiac hypertrophy. Mol Cell Biol. 2004; 24(14):6231-40. PMC: 434247. DOI: 10.1128/MCB.24.14.6231-6240.2004. View

13.

Goumans M, Lebrin F, Valdimarsdottir G . Controlling the angiogenic switch: a balance between two distinct TGF-b receptor signaling pathways. Trends Cardiovasc Med. 2003; 13(7):301-7. DOI: 10.1016/s1050-1738(03)00142-7. View

14.

Hariawala M, Horowitz J, Esakof D, Sheriff D, Walter D, Keyt B . VEGF improves myocardial blood flow but produces EDRF-mediated hypotension in porcine hearts. J Surg Res. 1996; 63(1):77-82. DOI: 10.1006/jsre.1996.0226. View

15.

Hedlund E, Hosaka K, Zhong Z, Cao R, Cao Y . Malignant cell-derived PlGF promotes normalization and remodeling of the tumor vasculature. Proc Natl Acad Sci U S A. 2009; 106(41):17505-10. PMC: 2752403. DOI: 10.1073/pnas.0908026106. View

16.

Villarreal F, Dillmann W . Cardiac hypertrophy-induced changes in mRNA levels for TGF-beta 1, fibronectin, and collagen. Am J Physiol. 1992; 262(6 Pt 2):H1861-6. DOI: 10.1152/ajpheart.1992.262.6.H1861. View

17.

Salomon D . Transforming growth factor β in cancer: Janus, the two-faced god. J Natl Cancer Inst. 2014; 106(2):djt441. PMC: 3937845. DOI: 10.1093/jnci/djt441. View

18.

Michele D, Gomez C, Hong K, Westfall M, Metzger J . Cardiac dysfunction in hypertrophic cardiomyopathy mutant tropomyosin mice is transgene-dependent, hypertrophy-independent, and improved by beta-blockade. Circ Res. 2002; 91(3):255-62. DOI: 10.1161/01.res.0000027530.58419.82. View

19.

Heinl-Green A, Radke P, Munkonge F, Frass O, Zhu J, Vincent K . The efficacy of a 'master switch gene' HIF-1alpha in a porcine model of chronic myocardial ischaemia. Eur Heart J. 2005; 26(13):1327-32. DOI: 10.1093/eurheartj/ehi223. View

20.

Wang J, Peng X, Lassance-Soares R, Najafi A, Alderman L, Sood S . Aging-induced collateral dysfunction: impaired responsiveness of collaterals and susceptibility to apoptosis via dysfunctional eNOS signaling. J Cardiovasc Transl Res. 2011; 4(6):779-89. PMC: 3756560. DOI: 10.1007/s12265-011-9280-4. View