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Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

1
Halal Research Center of IRI, FDA, Tehran, Iran
2
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3
Wihuri Research Institute, 00290 Helsinki, Finland
4
Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 9177948, Iran
5
Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland
6
Polish Mother’s Memorial Hospital Research Institute (PMMHRI), 93-338 Lodz, Poland
7
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
8
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
9
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948, Iran
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(12), 2047; https://doi.org/10.3390/jcm8122047
Received: 1 October 2019 / Revised: 9 November 2019 / Accepted: 11 November 2019 / Published: 21 November 2019
(This article belongs to the Section Vascular Medicine)
In atherosclerosis, macrophages in the arterial wall ingest plasma lipoprotein-derived lipids and become lipid-filled foam cells with a limited lifespan. Thus, efficient removal of apoptotic foam cells by efferocytic macrophages is vital to preventing the dying foam cells from forming a large necrotic lipid core, which, otherwise, would render the atherosclerotic plaque vulnerable to rupture and would cause clinical complications. Ca2+ plays a role in macrophage migration, survival, and foam cell generation. Importantly, in efferocytic macrophages, Ca2+ induces actin polymerization, thereby promoting the formation of a phagocytic cup necessary for efferocytosis. Moreover, in the efferocytic macrophages, Ca2+ enhances the secretion of anti-inflammatory cytokines. Various Ca2+ antagonists have been seminal for the demonstration of the role of Ca2+ in the multiple steps of efferocytosis by macrophages. Moreover, in vitro and in vivo experiments and clinical investigations have revealed the capability of Ca2+ antagonists in attenuating the development of atherosclerotic plaques by interfering with the deposition of lipids in macrophages and by reducing plaque calcification. However, the regulation of cellular Ca2+ fluxes in the processes of efferocytic clearance of apoptotic foam cells and in the extracellular calcification in atherosclerosis remains unknown. Here, we attempted to unravel the molecular links between Ca2+ and efferocytosis in atherosclerosis and to evaluate cellular Ca2+ fluxes as potential treatment targets in atherosclerotic cardiovascular diseases. View Full-Text
Keywords: atherosclerosis; Ca2+ homeostasis; calcification; calcium antagonists; cardiovascular diseases; efferocytosis; foam cells; macrophages; microRNA atherosclerosis; Ca2+ homeostasis; calcification; calcium antagonists; cardiovascular diseases; efferocytosis; foam cells; macrophages; microRNA
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MDPI and ACS Style

Tajbakhsh, A.; Kovanen, P.T.; Rezaee, M.; Banach, M.; Sahebkar, A. Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis. J. Clin. Med. 2019, 8, 2047. https://doi.org/10.3390/jcm8122047

AMA Style

Tajbakhsh A, Kovanen PT, Rezaee M, Banach M, Sahebkar A. Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis. Journal of Clinical Medicine. 2019; 8(12):2047. https://doi.org/10.3390/jcm8122047

Chicago/Turabian Style

Tajbakhsh, Amir; Kovanen, Petri T.; Rezaee, Mahdi; Banach, Maciej; Sahebkar, Amirhossein. 2019. "Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis" J. Clin. Med. 8, no. 12: 2047. https://doi.org/10.3390/jcm8122047

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