title: CCL19 and CCL21 modulate the inflammatory milieu in atherosclerotic lesions.
abstract: Despite advances in the pharmacologic and interventional treatment of coronary artery disease, atherosclerosis remains the leading cause of death worldwide. Atherosclerosis is a chronic inflammatory disease, and elevated expression of CCL19 and CCL21 has been observed in ruptured lesions of coronary arteries of patients with myocardial infarction and carotid plaques of patients with ischemic symptoms, as well as in plasma of coronary artery disease patients. However, the exact role of CCL19 and CCL21 in atherosclerosis remains unknown. In order to identify CCL19 and CCL21 as a novel therapeutic target, we performed bone marrow transplantation as an immunomodulatory treatment concept. Bone marrow of plt/plt mice (lacking CCL19 and CCL21-Ser) was transplanted into atherogenic Ldlr(-/-) mice. The study demonstrated a significantly increased inflammatory cellular infiltration into the lesions of plt/plt/Ldlr(-/-) mice versus controls. Although the level of chemoattraction was increased, messenger ribonucleic acid and protein levels in thoracic aorta and serum of several proinflammatory cytokines (TNFα, IFNγ, IL-6, IL-12, and IL-17) were significantly reduced in plt/plt/Ldlr(-/-) versus control mice. Increased influx, accompanied by reduced activation of leukocytes in atherosclerotic lesion, was accompanied by increased plaque stability but unchanged lesion development. In conclusion, modulation of the chemokines CCL19 and CCL21 represents a potent immunoregulatory treatment approach, and thus represents a novel therapeutic target to stabilize atherosclerotic lesions.
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Akhavanpoor
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Gleissner
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gorbatsch
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Doesch
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Akhavanpoor
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wangler
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Jahn
authors.affiliation: Institute of Pathology, University of Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Lasitschka
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Erbel
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D054415:Chemokine CCL19 / Q000172:deficiency / Q000378:metabolism*; D054421:Chemokine CCL21 / Q000172:deficiency / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D054415:Chemokine CCL19; D054421:Chemokine CCL21
keywords: atherosclerosis; bone marrow transplantation; chemokines; immunomodulatory therapy