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Atherosclerosis/Lipoproteins

High Plasma Levels of Heparin-Binding Epidermal Growth Factor Are Associated With a More Stable Plaque Phenotype and Reduced Incidence of Coronary Events

Sara Rattik, Maria Wigren, Harry Björkbacka, Gunilla Nordin Fredrikson, Bo Hedblad, Agneta Siegbahn, Eva Bengtsson, Alexandru Schiopu, Andreas Edsfeldt, Pontus Dunér, Helena Grufman, Isabel Gonçalves, Jan Nilsson
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https://doi.org/10.1161/ATVBAHA.114.304369
Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;ATVBAHA.114.304369
Originally published October 30, 2014
Sara Rattik
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Maria Wigren
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Harry Björkbacka
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Gunilla Nordin Fredrikson
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Bo Hedblad
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Agneta Siegbahn
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Eva Bengtsson
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Alexandru Schiopu
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Andreas Edsfeldt
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Pontus Dunér
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Helena Grufman
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Isabel Gonçalves
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Jan Nilsson
From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (S.R., M.W., H.B., G.N.F., B.H., E.B., A.S., A.E., P.D., H.G., I.G., J.N.); Department of Cardiology-Coronary diseases, Skåne University Hospital, Malmö, Sweden (A.S., A.E., I.G.); and Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (A.S.).
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Abstract

Objective—Rupture of atherosclerotic plaques is the major cause of acute coronary events (CEs). Plaque destabilization is the consequence of an imbalance between inflammatory-driven degradation of fibrous tissue and smooth muscle cell–dependent tissue repair. Proinflammatory factors have been documented extensively as biomarkers of cardiovascular risk but factors that contribute to stabilization of atherosclerotic plaques have received less attention. The present study aimed to investigate whether plasma levels of the smooth muscle cell growth factor epidermal growth factor (EGF), heparin-binding-EGF (HB-EGF), and platelet-derived growth factor correlate with plaque phenotype and incidence of CEs.

Approach and Results—HB-EGF, EGF and platelet-derived growth factor were measured in plasma from 202 patients undergoing carotid endarterectomy and in 384 incident CE cases and 409 matched controls recruited from the Malmö Diet and Cancer cohort. Significant positive associations were found between the plasma levels of all 3 growth factors and the collagen and elastin contents of the removed plaques. CE cases in the Malmö Diet and Cancer cohort had lower levels of HB-EGF in plasma, whereas no significant differences were found for EGF and platelet-derived growth factor. After adjusting for cardiovascular risk factors in a Cox proportional hazard model, the hazard ratio for the highest HB-EGF tertile was 0.61 (95% confidence interval, 0.47–0.82; P<0.001).

Conclusions—The associations between high levels of smooth muscle cell growth factors in plasma and a more fibrous plaque phenotype as well as the association between low levels of HB-EGF and incident CEs point to a potential clinically important role for factors that contribute to plaque stabilization by stimulating smooth muscle cells.

  • biomarkers
  • cardiovascular event
  • coronary disease
  • myocytes, smooth muscle
  • Received July 23, 2014.
  • Accepted October 16, 2014.
  • © 2014 American Heart Association, Inc.
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    High Plasma Levels of Heparin-Binding Epidermal Growth Factor Are Associated With a More Stable Plaque Phenotype and Reduced Incidence of Coronary Events
    Sara Rattik, Maria Wigren, Harry Björkbacka, Gunilla Nordin Fredrikson, Bo Hedblad, Agneta Siegbahn, Eva Bengtsson, Alexandru Schiopu, Andreas Edsfeldt, Pontus Dunér, Helena Grufman, Isabel Gonçalves and Jan Nilsson
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;ATVBAHA.114.304369, originally published October 30, 2014
    https://doi.org/10.1161/ATVBAHA.114.304369

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    High Plasma Levels of Heparin-Binding Epidermal Growth Factor Are Associated With a More Stable Plaque Phenotype and Reduced Incidence of Coronary Events
    Sara Rattik, Maria Wigren, Harry Björkbacka, Gunilla Nordin Fredrikson, Bo Hedblad, Agneta Siegbahn, Eva Bengtsson, Alexandru Schiopu, Andreas Edsfeldt, Pontus Dunér, Helena Grufman, Isabel Gonçalves and Jan Nilsson
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;ATVBAHA.114.304369, originally published October 30, 2014
    https://doi.org/10.1161/ATVBAHA.114.304369
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