Sara Rattik1, Maria Wigren2, Harry Björkbacka2, Gunilla Nordin Fredrikson2, Bo Hedblad2, Agneta Siegbahn2, Eva Bengtsson2, Alexandru Schiopu2, Andreas Edsfeldt2, Pontus Dunér2, Helena Grufman2, Isabel Gonçalves2, Jan Nilsson2. 1. 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.). Sara.Rattik@med.lu.se. 2. 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.).
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.
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.
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Authors: Faisel Khan; Isabel Gonçalves; Angela C Shore; Andrea Natali; Carlo Palombo; Helen M Colhoun; Gerd Östling; Francesco Casanova; Cecilia Kennbäck; Kunihiko Aizawa; Margaretha Persson; Kim M Gooding; David Strain; Helen Looker; Fiona Dove; Jill Belch; Silvia Pinnola; Elena Venturi; Michaela Kozakova; Jan Nilsson Journal: Cell Rep Med Date: 2022-07-19
Authors: Michael Lacy; Christina Bürger; Annelie Shami; Maiwand Ahmadsei; Holger Winkels; Katrin Nitz; Claudia M van Tiel; Tom T P Seijkens; Pascal J H Kusters; Ela Karshovka; Koen H M Prange; Yuting Wu; Sanne L N Brouns; Sigrid Unterlugauer; Marijke J E Kuijpers; Myrthe E Reiche; Sabine Steffens; Andreas Edsfeldt; Remco T A Megens; Johan W M Heemskerk; Isabel Goncalves; Christian Weber; Norbert Gerdes; Dorothee Atzler; Esther Lutgens Journal: Nat Commun Date: 2021-06-18 Impact factor: 14.919