**7. Cellular network in the intima**

the proportion of inflammatory cells increases, but these cells do not become predominating. Besides the smooth muscle cell antigen, resident intimal cells express pericyte antigens as well

What are the specific features of resident intimal cells? Morphological heterogeneity of intimal population consisting of processed cells of various shapes was described by Langhans [27], Schonfelder [62], Schlekunov [30, 63], Khavkin [64], Geer and Haust [19], and others. Elongated bipolar cells typical of the media predominate in the population of the muscular-elastic layer. At the same time, the cells of proteoglycan layer markedly vary in shape: they are elongated and stellate, with a variety of intermediate shapes. The presence of processed star-like cells [27]

The morphological forms of resident subendothelial cells (elongated and stellate) have been described in primary cultures of enzyme-isolated cells from normal and atherosclerotic human aorta [65]. Elongated cells have a long body without processes or with small side processes. They are packed in compact cell layers, express α-actin, and have a well-developed contractile apparatus [65]. Stellate (pericyte-like) cells have a round body with three or more processes. They are unevenly distributed in the loose connective-tissue matrix of the intima. In addition to α-actin, some juxtaluminally located cells express 3G5 and 2A7 pericytic antigens and CD68 macrophage-associated antigen [13], a scavenger receptor [39]. ln atherosclerotic lesions, the cytoplasm of these cells is filled with lipids (foam cells) [66]. Electron microscopic studies revealed considerable numbers of synthetic organelles in these cells [14]. In the atherosclerotic lesions, the number of stellate cells increases sixfold while the total number or cells and the number of elongated cells increase only twofold. Thus, both quantitative and qualitative changes occur in cellular composition of the intima underlying atherosclerotic lesions.

Is there any relationship between changes in cellular composition and the well-known manifestations of atherosclerosis such as intimal thickening and accumulation of lipids and collagen? The strongest correlation was established between the number of stellate cells, on the one hand, and the content of cholesteryl esters and total lipids, on the other [14]. The correlation coefficients between the number of stellate cells and collagen content and intimal thickness were somewhat lower; nevertheless, they remained greater than the correlation

Stellate cells are located in the close proximity to endothelial lining; they are the first barrier for the compounds entering the vascular wall from the blood. This may account for the great extent of the involvement of the stellate cells in atherosclerotic manifestations in the vascular

The direct correlation between the number of stellate cells and atherosclerotic manifestations raised a number of questions. Why do cells become stellate? Are stellate cells specific to cell type or does this shape reflect the functional state of a cell? In the human body, there are other

as the macrophage-associated antigen CD68.

212 Muscle Cell and Tissue

is the major characteristic of the proteoglycan-rich layer.

**6. Stellate cells and atherosclerosis-related manifestations**

coefficients for elongated cells and the total cell content [14].

wall [1, 14].

Based on the observations of *en face* preparations of the intima, Schonfelder [62] has suggested that stellate intimal cells are joined into a common network. He supposed that empty spaces between the interlaced cellular processes are the channels reaching deep into the intima.

The concept of a common cellular network in the intima of the human aorta was confirmed later [67]. Using scanning electron microscopy, it was shown that all cells in the proteoglycanrich layer of uninvolved intima are interconnected in the horizontal plane and form a common network [67]. The cells are also joined to each other in the vertical plane. Thus, a threedimensional cellular network is formed. All cell processes contact with the processes or bodies of other cells. Consequently, the proteoglycan-rich layer cannot be regarded as a sum of separated cells but as a unified cellular system. Empty spaces between the processes filled with the connective tissue matrix were also observed [67], as described by Schonfelder [62].

Cells of the muscular-elastic layer do not form a network characteristic of stellate cells in the proteoglycan-rich layer. Scanning electron microscopy showed that most of the cells have a bipolar elongated shape characteristic of medial smooth muscle cells. In the muscular-elastic layer, densely packed cells form strata oriented at a small angle to each other [67].

A continuous vertical gradient in the ratio between the number of stellate subendothelial cells and typical elongated smooth muscle cells has been discovered [67]. The number of elongated cells decreases from the muscular-elastic layer to the endothelium, while the number of network-forming stellate cells increases.

In atherosclerotic lesions, the cellular system of the intima undergoes considerable changes. In fatty streaks, many stellate cells are generally laden with lipids [14, 25, 66]. This may account for an increase in their dimensions and formation of surface bleb-like protrusions by lipid droplets and vesicles. Vesicles in the extracellular space were also found; this suggests that these vesicles are propagated by gemmation (budding) from the surface of the cells and cell processes. Vesicle gemmation from the ends of the cell processes can obviously lead to the degradation of intercellular contacts and dissociation of the common network. In atheroscler‐ otic plaques, changes in the cell system are more pronounced. In the superficial layers of the connective tissue cap, stellate cells are always settled as separate cells or small groups. Sometimes, these cells contain lipid inclusions. In deep layers of the intima, the number of processed cells increases, but they do not form a network. Interestingly, a three-dimensional cellular network typical of uninvolved intima was found in the intima next to the plaque shoulders displaying no visible atherosclerosis-related changes.
