Calmodulin expression distinguishes the smooth muscle cell population of human carotid plaque

Autor: Marie-Luce Bochaton-Piallat, Teresa Gagliano, Francesco Mascoli, Patricia M. Palagi, Carlotta Zerbinati, Giovanna Marchetti, Matteo Coen, Giuseppe Guastella, Francesco Bernardi
Rok vydání: 2012
Předmět:
Proteomics
Pathology
carotid plaque
Cell
Becaplermin
Gene Expression Regulation/drug effects
Cell Separation
ddc:616.07
030204 cardiovascular system & hematology
Cell Proliferation/drug effects
Pathogenesis
0302 clinical medicine
Restenosis
0303 health sciences
education.field_of_study
Endarterectomy
Carotid
Sulfonamides
Proto-Oncogene Proteins c-sis
musculoskeletal system
Phenotype
Immunohistochemistry
Plaque
Atherosclerotic
medicine.anatomical_structure
Carotid Arteries
cardiovascular system
VSMC
calmodulin
tissues
medicine.medical_specialty
Calmodulin
RNA
Messenger/genetics/metabolism
Sulfonamides/pharmacology
Population
Myocytes
Smooth Muscle
Biology
Culture Media
Conditioned/pharmacology
Pathology and Forensic Medicine
03 medical and health sciences
Calmodulin/antagonists & inhibitors/genetics/metabolism
medicine
Humans
RNA
Messenger
education
030304 developmental biology
Cell Proliferation
Cell Size
Proto-Oncogene Proteins c-sis/pharmacology
Cell growth
Macrophages/drug effects/metabolism/pathology
Macrophages
Carotid Arteries/drug effects/metabolism/pathology
Myocytes
Smooth Muscle/drug effects/metabolism/pathology
Plaque
Atherosclerotic/genetics/pathology
medicine.disease
Gene Expression Regulation
Culture Media
Conditioned
biology.protein
Zdroj: American Journal of Pathology, Vol. 183, No 3 (2013) pp. 996-1009
The American journal of pathology
ISSN: 1525-2191
0002-9440
Popis: Several observations suggest the expansion of a distinct medial smooth muscle cell (SMC) subset in atherosclerosis and restenosis. We characterized the phenotypic features of SMC subsets in cultures derived from human carotid endarterectomy specimens. Specimens comprised an undiseased portion (thin intimal thickening with the underlying media) and a diseased portion (atherosclerotic plaque with the underlying media). From plaque tissues of the diseased portion, only macrophage-derived foam cells were retrieved. From medial tissues, two SMC phenotypes were isolated: large SMCs (flat with a monolayered growth pattern, from the undiseased portion) and small SMCs (fusiform and growing in multilayers, from the undiseased and diseased portions after co-culture with macrophage-derived foam cells). Small SMCs displayed higher proliferative and migratory activities and were less differentiated than large SMCs. Proteomic analysis showed that calmodulin was predominant in small SMCs. Co-culture of large SMCs with macrophage-derived foam cells induced a transition to the small phenotype with increased calmodulin expression. The calmodulin inhibitor W-7 decreased the proliferation of small SMCs and prevented the large to small phenotypic transition. In vivo, calmodulin was markedly expressed in SMCs of atherosclerotic plaques and was barely detectable in the media. Macrophage-derived foam cells promote selective migration from the media of atheroma-prone SMCs characterized by calmodulin overexpression. Further studies of small SMCs could be instrumental in understanding atherosclerosis pathogenesis and in planning therapeutic strategies.
Databáze: OpenAIRE
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