MAGNUS BÄCK GROUP

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Lipid mediators

The lipoxygenase metabolism of fatty acids yields lipid mediators that may be either pro-inflammatory or mediate the resolution of inflammation. Our group has focused on the role of leukotrienes and their pathophysiological role in for example atherosclerosis, abdominal aortic aneurysms, in-stent restenosis, and aortic valve stenosis. We have also shown a potential beneficial role of anti-asthmatic leukotriene receptor antagonists for cardiovascular prevention in retrospective studies.

Other lipid mediators mediate the resolution of inflammation. For example, Aspirin-triggered lipoxin A4 (ATL) derived from arachidonic acid reduces intimal hyperplasia in experimental models. Similar lipid mediators can be formed from omega-3 fatty acids.

 
References:
 

Thul S, Labat C, Temmar M, Benetos A, Bäck M. Low salivary resolvin D1 to leukotriene B4 ratio predicts carotid intima media thickness: A novel biomarker of non-resolving vascular inflammation. Eur J Prev Cardiol. 2017 Jun;24(9):903-906.  

 

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

 

Petri MH, Laguna-Fernandez A, Tseng CN, Hedin U, Perretti M, Bäck M. Aspirin-triggered 15-epi-lipoxin A₄ signals through FPR2/ALX in vascular smooth muscle cells and protects against intimal hyperplasia after carotid ligation. Int J Cardiol. 2015 Jan 20;179:370-2. 

 

Bäck M, Powell WS, Dahlén SE, Drazen JM, Evans JF, Serhan CN, Shimizu T, Yokomizo T, Rovati GE. Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7. Br J Pharmacol. 2014 Aug;171(15):3551-74. Review.

 

Ingelsson E, Yin L, Bäck M. Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease. J Allergy Clin Immunol. 2012 Mar;129(3):702-707.

 

Bäck M. Inhibitors of the 5-lipoxygenase pathway in atherosclerosis. Curr Pharm Des. 2009;15(27):3116-32. Review.

Atherosclerosis

Atherosclerosis is a chronic inflammatory process triggered by accumulation of cholesterol-containing low density lipoproteins (LDL) particles in the arterial wall. Major etiological factors include hyperlipidemia, hypertension, diabetes, and cigarette smoking, all of which are thought to initiate and promote vascular inflammation.

We study several aspects of atherosclerosis to identify key pathways and targets with therapeutic potential. Our studies in this field range from experimental models to epidemiological and biomarker studies. One focus pathways for our studies is the lipid mediators of inflammation.

 
References:
 

Bäck M, Hansson GK. Anti-inflammatory therapies for atherosclerosis. Nat Rev Cardiol. 2015 Apr;12(4):199-211. Review.

 

Petri MH, Laguna-Fernández A, Gonzalez-Diez M, Paulsson-Berne G, Hansson GK, Bäck M. The role of the FPR2/ALX receptor in atherosclerosis development and plaque stability. Cardiovasc Res. 2015 Jan 1;105(1):65-74. 

 

Yin L, Lensmar C, Ingelsson E, Bäck M. Differential association of chronic obstructive pulmonary disease with myocardial infarction and ischemic stroke in a nation-wide cohort. Int J Cardiol. 2014 May 15;173(3):601-3. 

 

Petri MH, Tellier C, Michiels C, Ellertsen I, Dogné JM, Bäck M. Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells. Biochem Biophys Res Commun. 2013 Nov 15;441(2):393-8. 

 

Bäck M, Yin L, Ingelsson E. Cyclooxygenase-2 inhibitors and cardiovascular risk in a nation-wide cohort study after the withdrawal of rofecoxib. Eur Heart J. 2012 Aug;33(15):1928-33. 

Valvular Heart Disease

The heart valves, which maintain a unidirectional cardiac blood flow, are covered by endothelial cells and structurally composed by valvular interstitial cells and extracellular matrix. Valvular heart disease can be either stenotic, causing obstruction of the valvular flow, or regurgitant referring to a back-flow through the valve. The pathophysiological changes in valvular heart disease include for example lipid and inflammatory cell infiltration, calcification, neoangiogenesis, and extracellular matrix remodeling.

Our research on valvular heart disease span from molecular and cellular studies of valves and valve-derived cells to echocardiography research, biomarkers and epidemiology.

Read more about aortic valve stenosis here: https://emj.emg-health.com/wp-content/uploads/sites/2/2018/02/The-Quest-for-a-Medical-Treatment-of-Aortic-Stenosis-Putative-Therapeutic-Targets.pdf

 
References:
 

Bäck M, Hansson GK. Anti-inflammatory therapies for atherosclerosis. Nat Rev Cardiol. 2015 Apr;12(4):199-211. Review.

 

Petri MH, Laguna-Fernández A, Gonzalez-Diez M, Paulsson-Berne G, Hansson GK, Bäck M. The role of the FPR2/ALX receptor in atherosclerosis development and plaque stability. Cardiovasc Res. 2015 Jan 1;105(1):65-74. 

 

Yin L, Lensmar C, Ingelsson E, Bäck M. Differential association of chronic obstructive pulmonary disease with myocardial infarction and ischemic stroke in a nation-wide cohort. Int J Cardiol. 2014 May 15;173(3):601-3. 

 

Petri MH, Tellier C, Michiels C, Ellertsen I, Dogné JM, Bäck M. Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells. Biochem Biophys Res Commun. 2013 Nov 15;441(2):393-8. 

 

Bäck M, Yin L, Ingelsson E. Cyclooxygenase-2 inhibitors and cardiovascular risk in a nation-wide cohort study after the withdrawal of rofecoxib. Eur Heart J. 2012 Aug;33(15):1928-33. 

Biomarkers

Biomarkers for the prediction of cardiovascular risk and disease progression are being studied in our group as part of our translational approaches to coronary, cerebrovascular, and valvular disease.

 
References:
 

Thul S, Labat C, Temmar M, Benetos A, Bäck M. Low salivary resolvin D1 to leukotriene B4 ratio predicts carotid intima media thickness: A novel biomarker of non-resolving vascular inflammation. Eur J Prev Cardiol. 2017 Jun;24(9):903-906. 

 

Naar J, Jaye D, Linde C, Neužil P, Doškář P, Málek F, Braunschweig F, Lund LH, Mortensen L, Bäck M, Linderoth B, Lind G, Kueffer F, Koehler J, Shahgaldi K, Ståhlberg M. Spinal cord stimulation in heart failure: effect on disease-associated biomarkers. Eur J Heart Fail. 2017 Feb;19(2):283-286. 

 

Hoefer IE, Steffens S, Ala-Korpela M, Bäck M, Badimon L, Bochaton-Piallat ML, Boulanger CM, Caligiuri G, Dimmeler S, Egido J, Evans PC, Guzik T, Kwak BR, Landmesser U, Mayr M, Monaco C, Pasterkamp G, Tuñón J, Weber C; ESC Working Group Atherosclerosis and Vascular Biology. Novel methodologies for biomarker discovery in atherosclerosis. Eur Heart J. 2015 Oct 14;36(39):2635-42. Review.

 

Bäck M, Avignon A, Stanke-Labesque F, Boegner C, Attalin V, Leprieur E, Sultan A. Leukotriene production is increased in abdominal obesity.

PLoS One. 2014 Dec 1;9(12):e104593. Erratum in: PLoS One. 2015;10(1):e0117861.

 

Rafnsson A, Bäck M. Urinary leukotriene E4 is associated with renal function but not with endothelial function in type 2 diabetes. Dis Markers. 2013;35(5):475-80. 

 

Labat C, Temmar M, Nagy E, Bean K, Brink C, Benetos A, Bäck M. Inflammatory mediators in saliva associated with arterial stiffness and subclinical atherosclerosis. J Hypertens. 2013 Nov;31(11):2251-8.

Cardio-oncology

Previous radio- and/or chemotherapy may contribute to an increased cardiovascular risk in cancer survivors. In this context, we for example study a specific inflammatory profile in the adventitia of vascular specimens obtained after radiotherapy using experimental techniques, the effects of tyrosine kinase inhibitors on cardiovascular risk in retrospective cohort studies, and participate in clinical trials evaluating coronary flow reserve by echocardiography in patients under chemotherapy.

 
References:
 

Halle M, Christersdottir T, Bäck M. Chronic adventitial inflammation, vasa vasorum expansion, and 5-lipoxygenase up-regulation in irradiated arteries from cancer survivors. FASEB J. 2016 Nov;30(11):3845-3852.

 

Dahlén T, Edgren G, Lambe M, Höglund M, Björkholm M, Sandin F, Själander A, Richter J, Olsson-Strömberg U, Ohm L, Bäck M, Stenke L; Swedish CML Group and the Swedish CML Register Group. Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population-Based Cohort Study. Ann Intern Med. 2016 Aug 2;165(3):161-6. 

 

Selected Publications

Laguna-Fernandez A, Checa A, Carracedo M, Artiach G, Petri MH, Baumgartner R, Forteza MJ, Jiang X, Andonova T, Walker ME, Dalli J, Arnardottir H, Gisterå A, Thul S, Wheelock CE, Paulsson-Berne G, Ketelhuth DFJ, Hansson GK, Bäck M. ERV1/ChemR23 Signaling Protects from Artherosclerosis by Modifying oxLDL Uptake and Phagocystis in Macrophages. Circulation. 2018 Oct 16;138(16):1693-1705.

Larsson SC, Wolk A, Håkansson N, Bäck M. Overall and abdominal obesity and incident aortic valve stenosis: two prospective cohort studies. Eur Heart J. 2017 Jul 21;38(28):2192-2197.

 

Larsson SC, Wolk A, Bäck M. Alcohol consumption, cigarette smoking and incidence of aortic valve stenosis. J Intern Med. 2017 Oct;282(4):332-339. 

Laguna-Fernandez A, Carracedo M, Jeanson G, Nagy E, Eriksson P, Caligiuri G, Franco-Cereceda A, Bäck M. Iron alters valvular interstitial cell function and is associated with calcification in aortic stenosis. Eur Heart J. 2016 Dec 14;37(47):3532-3535. 

Thul S, Labat C, Temmar M, Benetos A, Bäck M. Low salivary resolvin D1 to leukotriene B4 ratio predicts carotid intima media thickness: A novel biomarker of non-resolving vascular inflammation. Eur J Prev Cardiol. 2017 Jun;24(9):903-906.

Petri MH, Laguna-Fernandez A, Arnardottir H, Wheelock CE, Perretti M, Hansson GK, Bäck M. Aspirin-triggered lipoxin A4 inhibits atherosclerosis progression in apolipoprotein E-/- mice. Br J Pharmacol. 2017 Nov;174(22):4043-4054.

 

Halle M, Christersdottir T, Bäck M. Chronic adventitial inflammation, vasa vasorum expansion, and 5-lipoxygenase up-regulation in irradiated arteries from cancer survivors. FASEB J. 2016 Nov;30(11):3845-3852. 

Bäck M, Hansson GK. Anti-inflammatory therapies for atherosclerosis. Nat Rev Cardiol. 2015 Apr;12(4):199-211. Review.

Petri MH, Laguna-Fernandez A, Tseng CN, Hedin U, Perretti M, Bäck M. Aspirin-triggered 15-epi-lipoxin A₄ signals through FPR2/ALX in vascular smooth muscle cells and protects against intimal hyperplasia after carotid ligation. Int J Cardiol. 2015 Jan 20;179:370-2. 

Petri MH, Laguna-Fernández A, Gonzalez-Diez M, Paulsson-Berne G, Hansson GK, Bäck M. The role of the FPR2/ALX receptor in atherosclerosis development and plaque stability. Cardiovasc Res. 2015 Jan 1;105(1):65-74. 

Nagy E, Andersson DC, Caidahl K, Eriksson MJ, Eriksson P, Franco-Cereceda A, Hansson GK, Bäck M. Upregulation of the 5-lipoxygenase pathway in human aortic valves correlates with severity of stenosis and leads to leukotriene-induced effects on valvular myofibroblasts. Circulation. 2011 Mar 29;123(12):1316-25.