Cellular subtype expression and activation of CaMKII regulate the fate of atherosclerotic plaque. (January 2017)

• Record Type: Journal Article
• Authors: Maione, Angela Serena; Cipolletta, Ersilia; Sorriento, Daniela; Borriello, Francesco; Soprano, Maria; Rusciano, Maria Rosaria; D'Esposito, Vittoria; Markabaoui, Abdul Karim; De Palma, Giovanni Domenico; Martino, Giovanni; Maresca, Lucio; Nobile, Giuseppe; Campiglia, Pietro; Formisano, Pietro; Ciccarelli, Michele; Marone, Gianni; Trimarco, Bruno; Iaccarino, Guido; Illario, Maddalena
• Is Part Of: Atherosclerosis. Volume 256(2017)
• Page Start: 53
• Page End: 61
• Publication Date: 2017-01
• Subjects: Atherosclerosis -- CaMKII -- VSMCs -- Macrophages -- Stable plaques -- Unstable plaques; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2016.11.006
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: 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. Methods: Clinically defined stable and unstable plaques obtained from patients undergoing carotid end arteriectomy were processed for evaluation of CaMKs protein expression, activity and localization. Results: 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. Conclusions: 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. Graphical abstract: Highlights: CaMKII plays a critical role in the molecular mechanism that regulate atherosclerotic plaque progression. The crosstalk between macrophages and VSMCs is regulated by CaMKII in atherosclerotic lesions. CaMKII levels are increased in stable plaque (SP), while unstable plaque (UnSP) have increased expression of CaMKIV. This study contributes to the understanding of the molecular mechanism underpinning atherosclerotic plaque progression.