**6. Smooth muscle cell phagocytosis**

Smooth muscle is found in multiple organ systems and can provide a variety of roles, often important for the physical functions of the organ or tissue in which they reside. Unlike skeletal muscle, smooth muscle involuntarily can maintain its tone over extended periods of time [158]. The functional cellular units of smooth muscle are described as nonstriated, in that they lack the sarcomeres that their skeletal striated counterparts possess. Smooth muscle cells are rich in actin and myosin which allows for efficient contraction [159]. It would be easy to describe smooth muscle cells (SMCs) as monofunctional and homogenous; however, it would appear that they have stromal-like properties and are capable of further differentiation into multiple "macrophage-like" phenotypes capable of phagocytosis [160]. The concept of phagocytosis by SMCs was first suggested observed in 1971 by Campbell and colleagues [161], and later confirmed by Garfield *et. al* in 1975, who demonstrated uptake of yeast and latex beads by guinea pig smooth muscle [14]. Like other nonprofessional phagocytes, SMCs express the phosphatidylserine receptor and functionally recognize phosphatidylserine-rich apoptotic bodies, resulting in efferocytosis [13, 16]. Like the other nonprofessional phagocytes discussed in this chapter, SMC phagocytosis has been studied and implicated in diseases, where pathological phagocytosis is considered to play a major role, such as atherosclerosis [162, 163]. In fact, SMC phagocytosis has been a focus of investigation in atherosclerosis.

#### *Non-Myeloid Cell Phagocytosis DOI: http://dx.doi.org/10.5772/intechopen.110583*

Atherosclerosis is the buildup of plaques in the subendothelial tissues of arterial macrovascular walls [164]. These plaques can obstruct blood flow through the arterial lumen, which can result in a series of vascular-related diseases. Atherosclerotic plaques comprise of "foam cells," which have phagocytosed low-density lipoproteins, which they are seemingly unable to efficiently process and resolve. Foam cells as active phagocytes are myeloid in origin, more specifically they are macrophages derived from monocytes [165] recruited into the subendothelial tissues as a result of vascular damage. However, foam cells of atherosclerotic plaques can also be derived from SMCs [49, 166], with some reports even suggesting the majority of foam cells in atherosclerotic legions to be of SMC origin [167]. Such SMCs resemble an undifferentiated precursor capable of a phenotypic switch under varying conditions [168]. The specific conditions that trigger SMCs to switch to a macrophage-like foam cell are not well known, although it appears to be KLF-4 dependent [169]. SMCs have a high abundance of LRP1, a key scavenger receptor for lipoproteins [170]. LRP1 activation will result in an influx of lipoproteins into the cell, generating a "foam cell" phenotype [171]. It is the inefficiency of SMC-derived foam cells as phagocytes that appears to be a significant factor in atherosclerosis. Despite the recognition that phagocytosis, or lack thereof, by SMCs is clearly playing a significant role in the pathophysiology of atherosclerosis, little is known about the internalization mechanism compared to the process of autophagy [172]. Studies to date have mainly focused their efforts to recreate SMC-derived foam cells and compare them to foam cells of macrophage origin in attempts to highlight key differences, instead of addressing the specific mechanisms relating to phagocytosis in SMC-derived foam cells.
