Next Article in Journal
Hospital Malnutrition, a Call for Political Action: A Public Health and NutritionDay Perspective
Previous Article in Journal
Interferons (IFN-A/-B/-G) Genetic Variants in Patients with Mixed Connective Tissue Disease (MCTD)
Open AccessReview

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), Lodz 93-338, 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.
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
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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop