Growth factor signaling in myocardial stress and fibrosis

Project Leader

Johanna Magga, Ph.D. (Pharm.)

Affiliation

Research unit of Biomedicine, Pharmacology and Toxicology, Faculty of Medicine, University of Oulu; Biocenter Oulu, University of Oulu, Finland

Mailing address

P.O.Box 5000, FIN-90014 University of Oulu, Finland

Street address

Aapistie 5B, 90220 Oulu, Finland

tel. +358-(0)294 485234

e-mail: johanna.magga(at)oulu.fi

About the project

Endothelial dysfunction, abnormal extracellular matrix production and cardiomyocyte hypertrophy are key elements of cardiovascular diseases, leading to impairment of left ventricular function. Sustained external load, in conditions such as hypertension, myocardial infarction or valvular disease, can evolve to a state of decompensated hypertrophy in a complicated progressive process known as myocardial remodeling. Remodeling involves rearrangement of the cardiomyocyte muscle fibers and alterations in cardiomyocyte metabolism, but also interstitial fibrosis, accumulation of extracellular matrix, and angiogenesis. Eventually, remodeling leads to heart failure. Non-muscle cells residing in the interstitium likely play important roles in both cardiac hypertrophy and heart failure.

Our aim is to investigate how growth factors regulate cardiomyocytes and the contribution of non-muscle cells to remodeling process. Our specific interest focuses on the actions of activins, bone morphogenetic proteins (BMP), and growth and differentiation factors (GDF), the members of the transforming growth factor-β (TGF) family of secreted growth factors. The effect of these factors on endothelial function and parenchymal cell homeostasis in the diseased myocardium remain mostly unknown.

By utilizing genetic and pharmacological tools in experimental models, we aim to identify the downstream signaling mechanisms of growth factors during myocardial ischemia-reperfusion injury and to investigate the role of growth factor signaling in development of cardiac hypertrophy, fibrosis and remodeling in the stressed myocardium. We also utilize human material to determine the role of these growth factors in cardiovascular diseases.

Please also see our extended research group home page: http://www.oulu.fi/mrc/research-groups/kerkela

Selected publications

Renko O, Tolonen AM, Rysä J, Magga J, Mustonen E, Ruskoaho H, Serpi R. SDF1 gradient associates with the distribution of c-Kit+ cardiac cells in the heart. Sci Rep. 2018 Jan 18;8(1):1160. doi: 10.1038/s41598-018-19417-8.

Perjés Á, Kilpiö T, Ulvila J, Magga J, Alakoski T, Szabó Z, Vainio L, Halmetoja E, Vuolteenaho O, Petäjä-Repo U, Szokodi I, Kerkelä R. Characterization of apela, a novel endogenous ligand of apelin receptor, in the adult heart. Basic Res Cardiol. 2016. Jan;111(1):2. doi: 10.1007/s00395-015-0521-6.

Tolonen AM, Magga J, Szabó Z, Viitala P, Gao E, Moilanen AM, Ohukainen P, Vainio L, Koch WJ, Kerkelä R, Ruskoaho H, Serpi R. Inhibition of Let-7 microRNA attenuates myocardial remodeling and improves cardiac function postinfarction in mice. Pharmacol Res Perspect. 2014. Aug;2(4):e00056. doi: 10.1002/prp2.56.

Szabó Z, Magga J, Alakoski T, Ulvila J, Piuhola J, Vainio L, Kivirikko KI, Vuolteenaho O, Ruskoaho H, Lipson KE, Signore P, Kerkelä R. Connective tissue growth factor inhibition attenuates left ventricular remodeling and dysfunction in pressure overload-induced heart failure. Hypertension. 2014. Jun;63(6):1235-40. doi: 10.1161/HYPERTENSIONAHA.114.03279.

Kaikkonen L, Magga J, Ronkainen VP, Koivisto E, Perjes A, Chuprun JK, Vinge LE, Kilpiö T, Aro J, Ulvila J, Alakoski T, Bibb JA, Szokodi I, Koch WJ, Ruskoaho H, Kerkelä R. p38α regulates SERCA2a function. J Mol Cell Cardiol. 2014. Feb;67:86-93. doi: 10.1016/j.yjmcc.2013.12.005.

Vainio L, Perjes A, Ryti N, Magga J, Alakoski T, Serpi R, Kaikkonen L, Piuhola J, Szokodi I, Ruskoaho H, Kerkelä R. Neuronostatin, a novel peptide encoded by somatostatin gene, regulates cardiac contractile function and cardiomyocyte survival. J Biol Chem. 2012. Feb 10;287(7):4572-80. doi: 10.1074/jbc.M111.289215.

Last updated: 17.4.2018