title: Effect of depletion of monocytes/macrophages on early aortic valve lesion in experimental hyperlipidemia.
abstract: Monocytes/macrophages are key players throughout atheroma development. The aim of this study was to determine the role of macrophages in lesion formation in heart valves in hyperlipidemia. We examined whether systemic depletion of monocytes/macrophages had a beneficial or adverse effect on the development of lesions in hyperlipemic hamsters injected twice weekly (for 2 months) with clodronate-encapsulated liposomes (H+Lclod), a treatment that selectively induces significant monocyte apoptosis. Hyperlipemic hamsters were employed as controls, as were hyperlipemic hamsters treated with plain liposomes. We assayed serum cholesterol (CH) and triglycerides (TG), the lipid and collagen contents and the size of the valve lesions, the matrix metalloproteinases (MMPs) in the serum and vessel wall, apolipoprotein E (ApoE), interleukin-1beta (IL-1beta), and superoxide anion production. In comparison with controls, H+Lclod hamsters exhibited: (1) increased lipid and collagen accumulation within the lesions, (2) decreased activity of MMP-9 and MMP-2 in sera and aortic homogenates, (3) decreased serum CH and TG and decreased expression of ApoE in sera and liver, (4) reduced expression of IL-1beta in aorta and liver homogenates, and (5) no change in the level of superoxide anion in the aorta. Thus, initially, the presence of the macrophages is beneficial in valvular lesion formation. Depletion of monocytes/macrophages is a two-edged sword having a beneficial effect by decreasing the expression of IL-1beta and MMP activities but an adverse effect by inducing a significant increase in the lipid and collagen content and expansion of valvular lesions.
authors.affiliation: Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania. manuela.calin@icbp.ro
authors.forename: Manuela Voinea
authors.initials: MV
authors.lastname: Calin
authors.forename: Ileana
authors.initials: I
authors.lastname: Manduteanu
authors.forename: Elena
authors.initials: E
authors.lastname: Dragomir
authors.forename: Emanuel
authors.initials: E
authors.lastname: Dragan
authors.forename: Manuela
authors.initials: M
authors.lastname: Nicolae
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Gan
authors.forename: Maya
authors.initials: M
authors.lastname: Simionescu
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D001057:Apolipoproteins E / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000473:pathology; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000187:drug effects; D006351:Heart Valves / Q000187:drug effects / Q000473:pathology*; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D047589:Leukocyte Reduction Procedures; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014020:Tissue Extracts
chemical_list: D001057:Apolipoproteins E; D053583:Interleukin-1beta; D008055:Lipids; D012333:RNA, Messenger; D014020:Tissue Extracts; D004002:Clodronic Acid; D013481:Superoxides; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9