The Increase of pFAK and THBS1 Protein and Gene Expression Levels in Vascular Smooth Muscle Cells by Histamine-treated M1 Macrophages
-
Mohsen Khosravi
,
Mohammad Najafi
,
Abdollah Amirfarhangi
,
Mahdi Karimi
,
Fahimeh Fattahi
,
Mohammad Shabani
Abstract
Atherosclerosis is developed due to the formation of atheroma plaques in the coronary arteries. In this process, M1 macrophages and vascular smooth muscle cells (VSMCs) are the main functional cells. Inflammatory mediators such as histamine may inflame M1 macrophages. The aim of this study was to determine the effect of M1 macrophage secretion contents on the gene and protein expression levels of focal adhesion kinase (FAK), vasodilator-stimulated phosphoprotein (VASP), and thrombospondin1 (THBS1). Whole blood samples from the six healthy subjects (stenosis<5%), and six patients (stenosis>70%) were prepared and peripheral blood mononuclear cells (PBMCs) were isolated. Then monocytes were differentiated into M1 macrophages using 100 ng/mL granulocyte-macrophage colony stimulating factor (GM-CSF). The differentiated M1 macrophages were treated with histamine (10-6 M), and their secretion contents were harvested and added to the culture medium of VSMCs. The FAK, VASP, and THBS1 gene expression and protein levels were measured using RT-qPCR and western blot techniques in VSMCs, respectively. The FAK and THBS1 gene expression levels significantly increased in VSMCs after adding secretion contents obtained from histamine-treated M1 macrophages (p=0.023 and 0.05, respectively), while significant results were not observed for VASP gene (p=0.45). In converse with the phosphorylated VASP (pVASP) (p<0.34), the phosphorylated FAK (pFAK) and THBS1 protein levels increased in VSMCs (p<0.001). We concluded that in inflammatory conditions, the immune events could affect the macrophages by histamine. The activated macrophages could locally activate signaling pathways via FAK and THBS1 genes that are effective in the proliferation and migration of VSMCs.
References:
(1) Fleming, R. Angina and coronary ischemia are the result of coronary regional blood flow differences. J Amer Coll Angiol 2003, 1, 127-142.
(2) Hansson, G. K.; Hermansson, A. The immune system in atherosclerosis. Nature immunology 2011, 12, 204.
(3) Li, X.; Fang, P.; Li, Y.; Kuo, Y.-M.; Andrews, A. J.; Nanayakkara, G.; Johnson, C.; Fu, H.; Shan, H.; Du, F. Mitochondrial reactive oxygen species mediate lysophosphatidylcholine-induced endothelial cell activation. Arteriosclerosis, thrombosis, and vascular biology 2016, ATVBAHA. 115.306964.
(4) Miller, J. D. Cardiovascular calcification: orbicular origins. Nature materials 2013, 12, 476.
(5) Schwartz, C. J.; Valente, A. J.; Sprague, E. A. Potential targets for stabilization and regression. Circulation 1997, 86, 117-123.
(6) Kimura, S.; Wang, K. Y.; Tanimoto, A.; Murata, Y.; Nakashima, Y.; Sasaguri, Y. Acute inflammatory reactions caused by histamine via monocytes/macrophages chronically participate in the initiation and progression of atherosclerosis. Pathology international 2004, 54, 465-474.
(7) Takagishi, T.; Sasaguri, Y.; Nakano, R.; Arima, N.; Tanimoto, A.; Fukui, H.; Morimatsu, M. Expression of the histamine H1 receptor gene in relation to atherosclerosis. The American journal of pathology 1995, 146, 981.
(8) Akdis, C. A.; Blaser, K. Histamine in the immune regulation of allergic inflammation. Journal of allergy and clinical immunology 2003, 112, 15-22.
(9) Ando, J.; Kamiya, A. Blood flow and vascular endothelial cell function. Frontiers of medical and biological engineering: the international journal of the Japan Society of Medical Electronics and Biological Engineering 1993, 5, 245-264.
(10) Chistiakov, D. A.; Orekhov, A. N.; Bobryshev, Y. V. Vascular smooth muscle cell in atherosclerosis. Acta physiologica 2015, 214, 33-50.
(11) Resovi, A.; Pinessi, D.; Chiorino, G.; Taraboletti, G. Current understanding of the thrombospondin-1 interactome. Matrix Biology 2014, 37, 83-91.
(12) Lawler, J. The functions of thrombospondin-1 and-2. Current opinion in cell biology 2000, 12, 634-640.
(13) Tulis, D. A. Novel protein kinase targets in vascular smooth muscle therapeutics. Current opinion in pharmacology 2017, 33, 12-16.
(14) He, M.; Gong, Y.; Shi, J.; Pan, Z.; Zou, H.; Sun, D.; Tu, X.; Tan, X.; Li, J.; Li, W. Plasma microRNAs as potential noninvasive biomarkers for in-stent restenosis. PloS one 2014, 9, e112043.
(15) Mills, C. M1 and M2 macrophages: oracles of health and disease. Critical Reviews™ in Immunology 2012, 32.
(16) Wang, K.-Y.; Arima, N.; Higuchi, S.; Shimajiri, S.; Tanimoto, A.; Murata, Y.; Hamada, T.; Sasaguri, Y. Switch of histamine receptor expression from H2 to H1 during differentiation of monocytes into macrophages. FEBS letters 2000, 473, 345-348.
(17) Sirois, J.; Ménard, G.; Moses, A. S.; Bissonnette, E. Y. Importance of histamine in the cytokine network in the lung through H2 and H3 receptors: stimulation of IL-10 production. The Journal of Immunology 2000, 164, 2964-2970.
(18) Triggiani, M.; Gentile, M.; Secondo, A.; Granata, F.; Taglialatela, M.; Annunziato, L.; Marone, G. Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H1 receptors. The Journal of Immunology 2001, 166, 4083-4091.
(19) Triggiani, M.; Petraroli, A.; Loffredo, S.; Frattini, A.; Granata, F.; Morabito, P.; Staiano, R. I.; Secondo, A.; Annunziato, L.; Marone, G. Differentiation of monocytes into macrophages induces the upregulation of histamine H1 receptor. Journal of Allergy and Clinical Immunology 2007, 119, 472-481.
(20) Higuchi, S.; Tanimoto, A.; Arima, N.; Xu, H.; Murata, Y.; Hamada, T.; Makishima, K.; Sasaguri, Y. Effects of histamine and interleukin‐4 synthesized in arterial intima on phagocytosis by monocytes/macrophages in relation to atherosclerosis. FEBS letters 2001, 505, 217-222.
(21) Yu, S.-H.; Huang, C.-Y.; Lee, S.-D.; Hsu, M.-F.; Wang, R.-Y.; Kao, C.-L.; Kuo, C.-H. Decreased eccentric exercise-induced macrophage infiltration in skeletal muscle after supplementation with a class of ginseng-derived steroids. PloS one 2014, 9, e114649.
(22) Seelamneni, H. Macrophage Polarization (M1/M2) and its Role in Wnt5a Secretion/Expression in Atherosclerosis. Ohio University, 2013.
(23) Bayer, C.; Varani, S.; Wang, L.; Walther, P.; Zhou, S.; Straschewski, S.; Bachem, M.; Söderberg-Naucler, C.; Mertens, T.; Frascaroli, G. Human cytomegalovirus infection of M1 and M2 macrophages triggers inflammation and autologous T-cell proliferation. Journal of virology 2013, 87, 67-79.
(24) Lopes, R. L.; Borges, T. J.; Araújo, J. F.; Pinho, N. G.; Bergamin, L. S.; Battastini, A. M. O.; Muraro, S. P.; Souza, A. P. D.; Zanin, R. F.; Bonorino, C. Extracellular mycobacterial DnaK polarizes macrophages to the M2-like phenotype. PLoS One 2014, 9, e113441.
(25) Tarique, A. A.; Logan, J.; Thomas, E.; Holt, P. G.; Sly, P. D.; Fantino, E. Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages. American journal of respiratory cell and molecular biology 2015, 53, 676-688.
(26) Iqbal, S.; Kumar, A. Characterization of in vitro generated human polarized macrophages. J Clin Cell Immunol 2015, 6, 4172.
(27) Li, G.; Jin, R.; Norris, R. A.; Zhang, L.; Yu, S.; Wu, F.; Markwald, R. R.; Nanda, A.; Conway, S. J.; Smyth, S. S. Periostin mediates vascular smooth muscle cell migration through the integrins ανβ3 and ανβ5 and focal adhesion kinase (FAK) pathway. Atherosclerosis 2010, 208, 358-365.
(28) Gambillara, V.; Thacher, T.; Silacci, P.; Stergiopulos, N. Effects of reduced cyclic stretch on vascular smooth muscle cell function of pig carotids perfused ex vivo. American journal of hypertension 2008, 21, 425-431.
(29) Park, H. S.; Quan, K. T.; Han, J. H.; Jung, S. H.; Lee, D. H.; Jo, E.; Lim, T. W.; Heo, K. S.; Na, M.; Myung, C. S. Rubiarbonone C inhibits platelet‐derived growth factor‐induced proliferation and migration of vascular smooth muscle cells through the focal adhesion kinase, MAPK and STAT3 Tyr705 signalling pathways. British journal of pharmacology 2017, 174, 4140-4154.
(30) Murphy-Ullrich, J. E.; Suto, M. J. Thrombospondin-1 regulation of latent TGF-β activation: A therapeutic target for fibrotic disease. Matrix Biology 2017.
(31) Moura, R.; Tjwa, M.; Vandervoort, P.; Holvoet, P.; Hoylaerts, M. F. Thrombospondin-1 deficiency accelerates atherosclerotic plaque maturation in ApoE−/− mice. Circulation research 2008, 103, 1181-1189.
(32) Moura, R.; Tjwa, M.; Vandervoort, P.; Cludts, K.; Hoylaerts, M. F. Thrombospondin-1 activates medial smooth muscle cells and triggers neointima formation upon mouse carotid artery ligation. Arteriosclerosis, thrombosis, and vascular biology 2007, 27, 2163-2169.
(33) Raman, P.; Krukovets, I.; Marinic, T. E.; Bornstein, P.; Stenina, O. I. Glycosylation mediates up-regulation of a potent antiangiogenic and proatherogenic protein, thrombospondin-1, by glucose in vascular smooth muscle cells. Journal of Biological Chemistry 2007, 282, 5704-5714.
(34) Lymn, J. S.; Rao, S. J.; Clunn, G. F.; Gallagher, K. L.; O’Neil, C.; Thompson, N. T.; Hughes, A. D. Phosphatidylinositol 3-kinase and focal adhesion kinase are early signals in the growth factor–like responses to thrombospondin-1 seen in human vascular smooth muscle. Arteriosclerosis, thrombosis, and vascular biology 1999, 19, 2133-2140.
(35) Gahtan, V.; Wang, X.-J.; Willis, A. I.; Tuszynski, G. P.; Sumpio, B. E. Thrombospondin-1 regulation of smooth muscle cell chemotaxis is extracellular signal-regulated protein kinases 1/2 dependent. Surgery 1999, 126, 203-207.
(36) Chen, X. J.; Squarr, A. J.; Stephan, R.; Chen, B.; Higgins, T. E.; Barry, D. J.; Martin, M. C.; Rosen, M. K.; Bogdan, S.; Way, M. Ena/VASP proteins cooperate with the WAVE complex to regulate the actin cytoskeleton. Developmental cell 2014, 30, 569-584.
| Files | ||
| Issue | Vol 18, No 1 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v18i1.632 | |
| Keywords | ||
| Atherosclerosis Focal adhesion kinase Histamine Macrophages Thrombospondin 1 Vascular smooth muscle cells Vasodilator-stimulated phosphoprotein | ||
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