Extracellular matrix macromolecules in health and disease – with special reference to cardiovascular diseases and cancer

​Description of Research

The aim of the research group is to understand in great detail the roles of specific extracellular matrix macromolecules, particularly proteoglycans and hyaluronan, in disease processes such as atherogenesis, excess angiogenesis and tumorigenesis. Currently we are in a process in developing decorin-based gene therapy for the treatment of human epithelial cancers (e.g. breast, bladder and colon cancers). We will also develop decorin-based gene therapy in the prevention of restenosis following angioplasty. In addition, as we have previously shown that decorin is a marked angiogenesis inhibitor, we are hoping to be able to develop decorin-based gene therapy to inhibit angiogenesis in situations where angiogenesis is not desired such as in tumorigenesis and diabetic microvascular complications.

Members of the research group

Annele Sainio, Ph.D
Marie Nyman, M.Sc.
Juho Mattila, M.D.
Collaborators (not named here)

Selected Publications

Schönherr E, Järveläinen HT, Sandell LJ, and Wight TN. Effects of platelet-derived growth factor and transforming growth factor-ß1 on the synthesis of a large versican-like chondroitin sulfate proteoglycan by arterial smooth muscle cells. J. Biol. Chem. 266: 17640-17647, 1991

Järveläinen HT, Kinsella MG, Wight TN, and Sandell LJ. Differential expression of small chondroitin/dermatan sulfate proteoglycans, PG-I/biglycan and PG-II/decorin, by vascular smooth muscle and endothelial cells in culture. J. Biol. Chem. 266: 23274-23281, 1991

Järveläinen HT, Iruela-Arispe ML, Kinsella MG, Sandell LJ, Sage EH, and Wight TN. Expression of decorin by sprouting bovine aortic endothelial cells exhibiting angiogenesis in vitro. Exp. Cell Res. 203: 395-401, 1992

Schönherr E, Järveläinen HT, Kinsella MG, Sandell LJ, and Wight TN. Platelet-derived growth factor and transforming growth factor-ß1 differentially affect the synthesis of biglycan and decorin by monkey arterial smooth muscle cells. Arterioscler. Thromb. 13: 1026-1036, 1993 (Current name of the journal: Arterioscler. Thromb. Vasc. Biol.)

Qwarnström EE, Järveläinen HT, Kinsella MG, Ostberg CO, Sandell LJ, Page RC, Wight TN. IL- 1ß regulation of fibroblast proteoglycan synthesis involves a decrease in versican steady-state mRNA levels. Biochem. J. 294: 613-620, 1993

Nikkari ST, Järveläinen HT, Wight TN, Ferguson M, and Clowes AW. Smooth muscle cell expression of extracellular matrix protein genes after arterial injury. Am. J. Pathol. 144: 1348-1356, 1994

Määttä A, Järveläinen HT, Nelimarkka LO, Penttinen RP. Fibroblast expression of collagens and proteoglycans is altered in aspartylglucosaminuria, a lysosomal storage disease. Biochim. Biophys. Acta, 1225: 264-270, 1994

Lammi MJ, Inkinen R, Parkkinen JJ, Häkkinen T, Jortikka M, Nelimarkka LO, Järveläinen HT,

Tammi MI. Expression of reduced amounts of structurally altered aggrecan in articular cartilage chondrocytes exposed to high hydrostatic pressure. Biochem. J. 304: 723-730, 1994 

Kainulainen V, Nelimarkka L, Järveläinen H, Laato M, Jalkanen M, Elenius K. Suppression ofsyndecan-1 expression in endothelial cells by tumour necrosis factor- a. J. Biol. Chem. 271: 18759 18766, 1996

Kinsella MG, Tsoi CK, Järveläinen HT, and Wight TN. Selective expression and processing of biglycan during migration of bovine aortic endothelial cells: The role of endogenous basic fibroblast growth factor. J. Biol. Chem. 272: 318-325, 1997

Nelimarkka L, Kainulainen V, Schönherr E, Moisander S, Jortikka M, Lammi M, Elenius K, Jalkanen M, and Järveläinen H. Expression of small extracellular chondroitin/dermatan sulfate proteoglycans is differentially regulated in human endothelial cells. J. Biol. Chem. 272: 12730-12737, 1997

Jortikka M, Parkkinen JJ, Inkinen RI, Kärner J, Järveläinen HT, Nelimarkka LO, Tammi MI, Lammi MJ. The role of microtubules in the regulation of proteoglycan synthesis in chondrocytes under hydrostatic pressure. Arch. Biochem. Biophys. 374: 172-180, 2000

Nelimarkka L, Salminen H, Kuopio T, Nikkari S, Ekfors T, Pelliniemi L, and Järveläinen H. Decorin is produced by capillary endothelial cells in inflammation-associated angiogenesis. Am. J. Pathol. 158:345-353, 2001

Järveläinen H, Vernon RB, Gooden MD, Francki A, Lara S, Johnson P, Kinsella MG, Sage EH, and Wight TN. Overexpression of decorin by rat arterial smooth muscle cells enhances contraction of type I collagen in vitro. Arterioscler. Thromb. Vasc. Biol. 24:67-72, 2004

Järveläinen H, Puolakkainen P, Pakkanen S, Brown EL, Höök M, Iozzo RV, Sage EH, and Wight TN. A role for decorin in cutaneous wound healing and angiogenesis. Wound Rep. Regen. 14: 443-452, 2006

Salomäki H, Sainio A, Söderström M, Pakkanen S, Laine J, and Järveläinen H. Differential expression of decorin by human malignant and benign vascular tumors. J. Histochem. Cytochem. 56: 639-646, 2008

Järveläinen H, Sainio A, Koulu M, Wight TN, Penttinen R. Extracellular matrix molecules: potential targets in pharmacotherapy. Pharmacol. Rev. 61: 198-223, 2009

Sainio A, Jokela T, Tammi MI, and Järveläinen H. Hyperglycemic conditions modulate connective tissue reorganization by human vascular smooth muscle cells through stimulation of hyaluronan synthesis. Glycobiology 20: 1117-1126, 2010

Oikonen M, Wendelin-Saarenhovi M, Siitonen N, Sainio A, Juonala M, Kähönen M, Lyytikäinen L-P, Lehtimäki T, Viikari JS, Järveläinen H, Raitakari OT. Tissue inhibitor of matrix metalloproteinases 4 (TIMP4) in a population of young adults: relations to cardiovascular risk markers and carotid artery intima-media thickness. The Cardiovaskular Risk in Young Finns Study. Scand. J. Clin. Lab. Invest. 72: 540-546, 2012

Boström P, Sainio A, Kakko T, Savontaus M, Söderström M, Järveläinen H. Localization of decorin gene expression in normal human breast tissue and in benign and malignant tumors of the human breast. Histochem. Cell. Biol. 139:161-171, 2013

Sainio A, Nyman M, Lund R, Vuorikoski R, Boström P, Boström PJ, Laato M, Järveläinen H. Lack of decorin expression by human bladder cancer cells offers new tools in the therapy of urothelial malignancies. PLoSOne 8: e76190, 2013

Sainio A, Järveläinen H. Extracellular matrix macromolecules in tumour microenvironment – with special reference to desmoplastic reaction and the role of matrix proteoglycans and hyaluronan. J. Carcinog. Mutagen. S13-002, 2013

Sainio A, Järveläinen H. Extracellular matrix macromolecules: potential tools and targets in cancer gene therapy. Mol. Cell Ther. 2: 14, 2014

Järveläinen H, Sainio A, Wight TN. Pivotal role of decorin in angiogenesis. Matrix Biol. 43: 15-26, 2015

Nyman MC, Sainio AO, Pennanen MM, Lund RJ, Vuorikoski S, Sundström JT, Järveläinen HT.  Decorin in human colon cancer. Localization in vivo and effect on cancer cell behavior in vitro. J. Histochem. Cytochem. 63: 710-720, 2015

Konki M, Pasumarthy K, Malonzo M, Sainio A, Valensisi C, Söderström M, Emani MR, Stubb A, Närvä E, Ghimire B, Laiho A, Järveläinen H, Lahesmaa R, Lähdesmäki H, Hawkins RD, Lund RJ. Epigenetic silencing of the key antioxidant enzyme catalase in karyotypically abnormal human pluripotent stem cells. Sci Rep. Nature 6: 22190, 2016



 Professor Hannu Järveläinen

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