Cardiopulmonary Research Group

Principal Investigator

Karl Lemström, MD, PhD
Docent in Transplantation Immunology, Consultant Cardiothoracic Surgeon
Transplantation Laboratory
Room: B425
Tel: +358 2941 26590, +358 50 427 2281
Fax +358 2941 1227
karl.lemstrom (at) helsinki.fi

Senior Scientist

Jussi Tikkanen, MD, PhD
Antti Nykänen, MD, PhD
Janne Jokinen, MD, PhD

Graduate Students

Rainer Krebs, MSc
Mikko Keränen, MD
Raimo Tuuminen, MD
Jussi Ropponen, MD

Undergraduate Students

Simo Syrjälä, MB
Alireza Raissadati, MB

Technician

Eeva Rouvinen, RN

Laboratory: B412
Office: B410B
Tel: +358 2941 26585 (laboratory)
Tel: +358 2941 26582 (office)

Research Interests

Chronic rejection is the major limitation hindering long-term survival of heart and lung allograft recipients and has a major role in renal allograft loss. Although currently used immunosuppressive drugs prevent acute rejection, they do not prevent signals that bridge innate and adaptive immune responses, nor the pathologial fibrobroliferation that leads to chronic rejection. Therefore, new strategies that target at other critical pathways than T cell proliferation are required to increase the long-term survival of allograft recipients.

Our results indicate that allograft blood and lymphatic vessels, and their growth factors such as hypoxia-inducible factor -1, VEGF, PDGF and angiopoietins, have important roles in allograft ischemia-reperfusion injury, immune cell trafficking, and development of acute and chronic rejection. We aim to investigate in detail the pathologic role of vascular dysfunction and vascular growth factors in allografts using experimental heart and lung transplantation models, and target critical pathways with gene transfer, monoclonal antibodies and small molecular peptides.

Our groups emphasizes translational research and we aim to transfer the results of our basic research into the clinical setting. A clinical study investigating the effect of simvastatin treatment of transplant donors on ischemia-reperfusion injury is currently going on.

Selected Publications

• Nykänen AI, Sandelin H, Krebs R, Keränen MA, Tuuminen R, Kärpänen T, Wu Y, Pytowski B, Koskinen PK, Ylä-Herttuala S, Alitalo K, Lemström KB. Targeting lymphatic vessel activation and CCL21 production by vascular endothelial growth factor receptor-3 inhibition has novel immunomodulatory and antiarteriosclerotic effects in cardiac allografts. Circulation. 2010;121:1413-22.

• Tuuminen R, Nykänen AI, Krebs R, Soronen J, Pajusola K, Keränen MA, Koskinen PK, Alitalo K, Lemström KB. PDGF-A, -C, and -D but not PDGF-B increase TGF-beta1 and chronic rejection in rat cardiac allografts. Arterioscler Thromb Vasc Biol. 2009;29:691-8.

• Raisky O, Nykänen AI, Krebs R, Hollmén M, Keränen MA, Tikkanen JM, Sihvola R, Alhonen L, Salven P, Wu Y, Hicklin DJ, Alitalo K, Koskinen PK, Lemström KB. VEGFR-1 and -2 regulate inflammation, myocardial angiogenesis, and arteriosclerosis in chronically rejecting cardiac allografts. Arterioscler Thromb Vasc Biol. 2007;27:819-25.

• Tikkanen JM, Hollmén M, Nykänen AI, Wood J, Koskinen PK, Lemström KB. Role of platelet-derived growth factor and vascular endothelial growth factor in obliterative airway disease. Am J Respir Crit Care Med. 2006;174:1145-52.

• Nykänen AI, Krebs R, Saaristo A, Turunen P, Alitalo K, Ylä-Herttuala S, Koskinen PK, Lemström KB. Angiopoietin-1 protects against the development of cardiac allograft arteriosclerosis. Circulation. 2003;107:1308-14.