Behaviours. Significantly, additionally they 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 IL-5 Proteins Gene ID macrophage marker CD68. These benefits directly demonstrate that SMCs may swiftly undergo phenotypic modulation and develop phagocytic capabilities. Resident SMCs could present a possible source of macrophages in vascular remodelling.(Resubmitted 28 April 2016; accepted immediately after revision 26 June 2016; initially published on the internet 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, bovine serum albumin; CA, carotid artery; CCh, carbachol; EC, endothelial cell; FBS, fetal bovine serum; InsP3 , inositol 1,4,5-trisphosphate; PDGF-BB, platelet-derived EGF Protein Formula growth 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 on the Physiological SocietyDOI: 10.1113/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, supplied the original operate is correctly cited.M. E. Sandison and othersJ Physiol 594.Introduction Atherosclerosis requires the focal build-up of smooth muscle cells (SMCs) and macrophages below the endothelium in arteries (Ross, 1999). Macrophages may well accumulate inside the vascular wall simply because circulating monocytes adhere towards the endothelium, migrate to the subendothelial space and differentiate into macrophages. These macrophage express scavenger receptors that facilitate the uptake of modified lipoproteins major to cholesterol accumulation plus the appearance of `foam cells’. Macrophage-derived foam cells make up the fatty streak lesions that precede a lot more sophisticated atherosclerotic plaques. However, in plaques, cells classified as macrophage (e.g. from CD68 expression) may perhaps also express proteins more typically related with SMCs (Mietus-Snyder et al. 2000; Allahverdian et al. 2014), e.g. SM -actin (SMA) and SM22. In human coronary arteries, one example is, 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). As a result, macrophage cells co-expressing smooth muscle (SM) markers may possibly 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 to the proposal that SM might acquire a macrophage phenotype (Gomez et al. 2013; Allahverdian et al. 2014; Feil et al. 2014). The capacity 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. Having said that, the extent as well as the existence of phenotypic modulation has lately been questioned (Holifield et al. 1996; Tang et al. 2012, 2013; Nguyen et al. 201.