title: Plasma fibronectin deficiency impedes atherosclerosis progression and fibrous cap formation.
abstract: Atherosclerotic lesions are asymmetric focal thickenings of the intima of arteries that consist of lipids, various cell types and extracellular matrix (ECM). These lesions lead to vascular occlusion representing the most common cause of death in the Western world. The main cause of vascular occlusion is rupture of atheromatous lesions followed by thrombus formation. Fibronectin (FN) is one of the earliest ECM proteins deposited at atherosclerosis-prone sites and was suggested to promote atherosclerotic lesion formation. Here, we report that atherosclerosis-prone apolipoprotein E-null mice lacking hepatocyte-derived plasma FN (pFN) fed with a pro-atherogenic diet display dramatically reduced FN depositions at atherosclerosis-prone areas, which results in significantly smaller and fewer atherosclerotic plaques. However, the atherosclerotic lesions from pFN-deficient mice lacked vascular smooth muscle cells and failed to develop a fibrous cap. Thus, our results demonstrate that while FN worsens the course of atherosclerosis by increasing the atherogenic plaque area, it promotes the formation of the protective fibrous cap, which in humans prevents plaques rupture and vascular occlusion.
authors.affiliation: Department for Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Rohwedder
authors.forename: Eloi
authors.initials: E
authors.lastname: Montanez
authors.forename: Karsten
authors.initials: K
authors.lastname: Beckmann
authors.forename: Eva
authors.initials: E
authors.lastname: Bengtsson
authors.forename: Pontus
authors.initials: P
authors.lastname: Dunér
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000097:blood*; D005355:Fibrosis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic
chemical_list: D001057:Apolipoproteins E; D005353:Fibronectins; D018836:Inflammation Mediators; C045073:Cre recombinase; D019426:Integrases