Behaviours. Significantly, they also displayed clear proof of phagocytic activity. This macrophage-like behaviour was confirmed by their internalisation of 1 m fluorescent latex beads. Even so, migratory SMCs did not uptake acetylated low-density lipoprotein or express the classic macrophage marker CD68. These results directly demonstrate that SMCs may well rapidly undergo phenotypic modulation and create phagocytic capabilities. Resident SMCs might present a prospective source of macrophages in vascular remodelling.(Resubmitted 28 April 2016; accepted right after revision 26 June 2016; initial published on line 9 July 2016) Corresponding author J. G. McCarron: Strathclyde Institute of Pharmacy and Biomedical Sciences, 161 Cathedral St, Glasgow G4 0RE, UK. E mail: [email protected] Abbreviations AcLDL, acetylated low-density lipoprotein; BSA, CXCR3 site bovine serum albumin; CA, ALDH1 medchemexpress carotid artery; CCh, carbachol; EC, endothelial cell; FBS, fetal bovine serum; InsP3 , inositol 1,four,5-trisphosphate; PDGF-BB, platelet-derived development factor-BB; PE, phenylephrine; PV, portal vein; SM, smooth muscle; SMA, smooth muscle -actin; SMC, smooth muscle cell; SM-MHC, smooth muscle myosin heavy chain; TMRE, tetramethylrhodamine.C2016 The Authors. The Journal of Physiology published by John Wiley Sons Ltd on behalf of your Physiological SocietyDOI: ten.1113/JPThis is an open access write-up under the terms on the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, offered the original operate is adequately cited.M. E. Sandison and othersJ Physiol 594.Introduction Atherosclerosis requires the focal build-up of smooth muscle cells (SMCs) and macrophages under the endothelium in arteries (Ross, 1999). Macrophages may well accumulate in the vascular wall for the reason that circulating monocytes adhere for the endothelium, migrate for the subendothelial space and differentiate into macrophages. These macrophage express scavenger receptors that facilitate the uptake of modified lipoproteins leading to cholesterol accumulation plus the look of `foam cells’. Macrophage-derived foam cells make up the fatty streak lesions that precede extra advanced atherosclerotic plaques. Having said that, in plaques, cells classified as macrophage (e.g. from CD68 expression) may perhaps also express proteins far more generally linked with SMCs (Mietus-Snyder et al. 2000; Allahverdian et al. 2014), e.g. SM -actin (SMA) and SM22. In human coronary arteries, for instance, 50 of foam cell-rich lesions had co-localisation of foam cell markers and SMA (Allahverdian et al. 2014). It has also been reported that human monocytes can undergo a transition to a SMA-expressing myofibroblast-like phenotype (Stewart et al. 2009). Hence, macrophage cells co-expressing smooth muscle (SM) markers may well be macrophage cells with SM markers or SM-like cells with macrophage markers (Stewart et al. 2009; Ludin et al. 2012; Shen et al. 2012; Andreeva et al. 1997). Recent experimental observations have led for the proposal that SM may possibly obtain a macrophage phenotype (Gomez et al. 2013; Allahverdian et al. 2014; Feil et al. 2014). The ability of contractile SMCs to dedifferentiate into a synthetic, migratory phenotype (generally known as phenotypic modulation) is uncommon amongst differentiated cells and is believed to underlie vascular remodelling in atherosclerosis. However, the extent and in some cases the existence of phenotypic modulation has lately been questioned (Holifield et al. 1996; Tang et al. 2012, 2013; Nguyen et al. 201.