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About me

Senior research fellow of Cardiovascular Immunology


1999                    Biochemical-pharmacist - Faculty of Pharmaceutical Sciences, University of São Paulo (USP), Riberião Preto, Brazil.

2005                    PhD in immunology. Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, Brazil.

2005 – 2010        Postdoctoral fellow, Experimental Cardiovascular Research Unit, CMM, Karolinska University Hospital, Stockholm, Sweden.

Research description

Heart disease and stroke, largely due to atherosclerosis and atherothrombosis, are the major causes of death in the western world and increasingly so in developing countries.

Atherosclerosis is a chronic inflammatory disease in which lipids accumulate, eliciting an inflammatory response in the arterial wall. Atherothrombosis, defined as disruption of the atherosclerotic plaque and superimposed thrombosis, accounts for most of the lethal consequences of atherosclerosis. These life-threatening complications of atherosclerotic cardiovascular diseases (CVD) are linked primarily to an acute complication that is caused by prothrombotic changes in the plaque, including weakening of the fibrous cap, plaque disruption, and exposure of the core’s procoagulant material to coagulation proteins and platelets in the blood.

The aim of our research is to develop new therapeutic approaches for the prevention and treatment of atherosclerotic CVDs. An important aspect of our projects is to identify new drug candidates that can 1) influence blood lipid levels, 2) reduce ongoing inflammation in the vessel wall, 3) promote plaque stabilization, and 4) decrease risk of thrombosis.

Our recent work revealed that the Kynurenine pathway of tryptophan degradation, which lays downstream of Indoleamine 2,3-dioxygenase (IDO), is a very attractive target for the development of novel therapies. Our current projects aim at investigating the mechanisms by which the Kynurenine pathway of tryptophan degradation regulates lipid metabolism, macrophage and smooth muscle cell responses, and platelet activation—all events that can influence plaque formation, stabilization, rupture, and thrombus formation.


List of Publications

Inhibition of indoleamine 2,3-dioxygenase promotes vascular inflammation and increases atherosclerosis in Apoe-/- mice.
Polyzos K, Ovchinnikova O, Berg M, Baumgartner R, Agardh H, Pirault J, et al
Cardiovasc. Res. 2015 May;106(2):295-302

Sterile inflammation in the spleen during atherosclerosis provides oxidation-specific epitopes that induce a protective B-cell response.
Grasset E, Duhlin A, Agardh H, Ovchinnikova O, Hägglöf T, Forsell M, et al
Proc. Natl. Acad. Sci. U.S.A. 2015 Apr;112(16):E2030-8

The role of the kynurenine pathway of tryptophan metabolism in cardiovascular disease. An emerging field.
Polyzos K, Ketelhuth D
Hamostaseologie 2015 ;35(2):128-36

Modulation of autoimmunity and atherosclerosis - common targets and promising translational approaches against disease.
Ketelhuth D, Hansson G
Circ. J. 2015 ;79(5):924-33

Toll-Like Receptor 3 Influences Glucose Homeostasis and β-Cell Insulin Secretion.
Strodthoff D, Ma Z, Wirström T, Strawbridge R, Ketelhuth D, Engel D, et al
Diabetes 2015 Oct;64(10):3425-38

The leukotriene B4 receptor (BLT) antagonist BIIL284 decreases atherosclerosis in ApoE-/- mice.
Ketelhuth D, Hermansson A, Hlawaty H, Letourneur D, Yan Z, Bäck M
Prostaglandins Other Lipid Mediat. 2015 Sep;121(Pt A):105-9

Apolipoprotein B100 danger-associated signal 1 (ApoBDS-1) triggers platelet activation and boosts platelet-leukocyte proinflammatory responses.
Assinger A, Wang Y, Butler L, Hansson G, Yan Z, Söderberg-Nauclér C, et al
Thromb. Haemost. 2014 Aug;112(2):332-41

Mycobacterium bovis BCG killed by extended freeze-drying induces an immunoregulatory profile and protects against atherosclerosis.
Ovchinnikova O, Berge N, Kang C, Urien C, Ketelhuth D, Pottier J, et al
J. Intern. Med. 2014 Jan;275(1):49-58

Transforming growth factor-β signaling in T cells promotes stabilization of atherosclerotic plaques through an interleukin-17-dependent pathway.
Gisterå A, Robertson A, Andersson J, Ketelhuth D, Ovchinnikova O, Nilsson S, et al
Sci Transl Med 2013 Jul;5(196):196ra100

Lack of invariant natural killer T cells affects lipid metabolism in adipose tissue of diet-induced obese mice.
Strodthoff D, Lundberg A, Agardh H, Ketelhuth D, Paulsson-Berne G, Arner P, et al
Arterioscler. Thromb. Vasc. Biol. 2013 Jun;33(6):1189-96

T cell-based therapies for atherosclerosis.
Ketelhuth D, Gisterå A, Johansson D, Hansson G
Curr. Pharm. Des. 2013 ;19(33):5850-8

Depletion of FOXP3+ regulatory T cells promotes hypercholesterolemia and atherosclerosis.
Klingenberg R, Gerdes N, Badeau R, Gisterå A, Strodthoff D, Ketelhuth D, et al
J. Clin. Invest. 2013 Mar;123(3):1323-34

Toll-like receptor 3 and 4 signalling through the TRIF and TRAM adaptors in haematopoietic cells promotes atherosclerosis.
Lundberg A, Ketelhuth D, Johansson M, Gerdes N, Liu S, Yamamoto M, et al
Cardiovasc. Res. 2013 Jul;99(2):364-73

The tryptophan metabolite 3-hydroxyanthranilic acid lowers plasma lipids and decreases atherosclerosis in hypercholesterolaemic mice.
Zhang L, Ovchinnikova O, Jönsson A, Lundberg A, Berg M, Hansson G, et al
Eur. Heart J. 2012 Aug;33(16):2025-34

Identification of a danger-associated peptide from apolipoprotein B100 (ApoBDS-1) that triggers innate proatherogenic responses.
Ketelhuth D, Rios F, Wang Y, Liu H, Johansson M, Fredrikson G, et al
Circulation 2011 Nov;124(22):2433-43, 1-7

Cellular immunity, low-density lipoprotein and atherosclerosis: break of tolerance in the artery wall.
Ketelhuth D, Hansson G
Thromb. Haemost. 2011 Nov;106(5):779-86

Subcutaneous immunization with heat shock protein-65 reduces atherosclerosis in Apoe⁻/⁻ mice.
Klingenberg R, Ketelhuth D, Strodthoff D, Gregori S, Hansson G
Immunobiology 2012 May;217(5):540-7

Immunotherapy with tolerogenic apolipoprotein B-100-loaded dendritic cells attenuates atherosclerosis in hypercholesterolemic mice.
Hermansson A, Johansson D, Ketelhuth D, Andersson J, Zhou X, Hansson G
Circulation 2011 Mar;123(10):1083-91

The role of matrix metalloproteinases in atherothrombosis.
Ketelhuth D, Bäck M
Curr Atheroscler Rep 2011 Apr;13(2):162-9

Inhibition of T cell response to native low-density lipoprotein reduces atherosclerosis.
Hermansson A, Ketelhuth D, Strodthoff D, Wurm M, Hansson E, Nicoletti A, et al
J. Exp. Med. 2010 May;207(5):1081-93

High-density lipoprotein inhibits the uptake of modified low- density lipoprotein and the expression of CD36 and FcgammaRI.
Carvalho M, Vendrame C, Ketelhuth D, Yamashiro-Kanashiro E, Goto H, Gidlund M
J. Atheroscler. Thromb. 2010 Aug;17(8):844-57

Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36 recruitment into the same lipid rafts.
Rios F, Ferracini M, Pecenin M, Koga M, Wang Y, Ketelhuth D, et al
PLoS ONE 2013 ;8(10):e76893

Matrix metalloproteinases in atherothrombosis.
Bäck M, Ketelhuth D, Agewall S
Prog Cardiovasc Dis ;52(5):410-28

Intranasal immunization with an apolipoprotein B-100 fusion protein induces antigen-specific regulatory T cells and reduces atherosclerosis.
Klingenberg R, Lebens M, Hermansson A, Fredrikson G, Strodthoff D, Rudling M, et al
Arterioscler. Thromb. Vasc. Biol. 2010 May;30(5):946-52

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