title: Cellular subtype expression and activation of CaMKII regulate the fate of atherosclerotic plaque.
abstract: Atherosclerosis is a degenerative process of the arterial wall implicating activation of macrophages and proliferation of vascular smooth muscle cells. Calcium-calmodulin dependent kinase type II (CaMKII) in vascular smooth muscle cells (VSMCs) regulates proliferation, while in macrophages, this kinase governs diapedesis, infiltration and release of extracellular matrix enzymes. We aimed at understanding the possible role of CaMKII in atherosclerosis plaques to regulate plaque evolution towards stability or instability.
  
  
  
  Clinically defined stable and unstable plaques obtained from patients undergoing carotid end arteriectomy were processed for evaluation of CaMKs protein expression, activity and localization.
  
  
  
  The larger content of CaMKII was found in CD14+myeloid cells that were more abundant in unstable rather than stable plaques. To test the biological effect of activated CD14+myeloid cells, VSMCs were exposed to the conditioned medium (CM) of macrophages extracted from carotid plaques. CM induced attenuation of CaMKs expression and activity in VSMCs, leading to the reduction of VSMCs proliferation. This appears to be due to the CaMKII dependent release of cytokines.
  
  
  
  These results indicate a pivotal role of CaMKs in atherosclerosis by regulating activated myeloid cells on VSMCs activity. CaMKII could represent a possible target for therapeutic strategies based on macrophages specific inhibition for the stabilization of arteriosclerotic lesions.
authors.affiliation: Department of Translational Medical Science, Federico II University, Naples, Italy.
authors.forename: Angela Serena
authors.initials: AS
authors.lastname: Maione
authors.affiliation: Department of Medicine, Surgery Odontoiatrics-Scuola Medica Salernitana, University of Salerno, Salerno, Italy.
authors.forename: Ersilia
authors.initials: E
authors.lastname: Cipolletta
authors.affiliation: Department of Advanced Biomedical Science, Federico II University, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sorriento
authors.affiliation: Department of Translational Medical Science, Federico II University, Naples, Italy; Center for Basic and Clinical Immunology Research (CISI), Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Borriello
authors.affiliation: Department of Translational Medical Science, Federico II University, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Soprano
authors.affiliation: Department of Translational Medical Science, Federico II University, Naples, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Rusciano
authors.affiliation: Department of Translational Medical Science, Federico II University, Naples, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: D'Esposito
authors.affiliation: Department of Gastroenterology, Endocrinology and Surgery, Federico II University, Naples, Italy.
authors.forename: Abdul Karim
authors.initials: AK
authors.lastname: Markabaoui
authors.affiliation: Department of Gastroenterology, Endocrinology and Surgery, Federico II University, Naples, Italy.
authors.forename: Giovanni Domenico
authors.initials: GD
authors.lastname: De Palma
authors.affiliation: Department of Gastroenterology, Endocrinology and Surgery, Federico II University, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martino
authors.affiliation: AziendadeiColli Hospital, Department of Vascular Surgery, Naples, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Maresca
authors.affiliation: AziendadeiColli Hospital, Department of Vascular Surgery, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nobile
authors.affiliation: Department of Pharmacy, University of Salerno, Salerno, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.affiliation: Department of Translational Medical Science, Federico II University, Naples, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Formisano
authors.affiliation: Department of Medicine, Surgery Odontoiatrics-Scuola Medica Salernitana, University of Salerno, Salerno, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Ciccarelli
authors.affiliation: Department of Translational Medical Science, Federico II University, Naples, Italy; Center for Basic and Clinical Immunology Research (CISI), Italy; CNR Institute of Experimental Endocrinology and Oncology "G. Salvatore", Naples, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Marone
authors.affiliation: Department of Advanced Biomedical Science, Federico II University, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.affiliation: Department of Medicine, Surgery Odontoiatrics-Scuola Medica Salernitana, University of Salerno, Salerno, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Iaccarino
authors.affiliation: Department of Translational Medical Science, Federico II University, Naples, Italy; Federico II University and Hospital, Naples, Italy. Electronic address: illario@unina.it.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Illario
mesh_terms: D000368:Aged; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002339:Carotid Arteries / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016894:Endarterectomy, Carotid; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000473:pathology; D058226:Plaque, Atherosclerotic; D012422:Rupture, Spontaneous; D013997:Time Factors
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Atherosclerosis; CaMKII; Macrophages; Stable plaques; Unstable plaques; VSMCs