Abstract
Myocardial infarctions and cerebrovascular accidents are the most common causes of death in the United States. These health conditions are caused by vascular injuries, which initiate the inflammatory response and have the capability to develop into plaque. This process of plaque accumulation is termed atherosclerosis and is characterized as fatty, cartilaginous, bony tissue, which create plaque lesions in blood vessels/arteries. Previous research provides a dedifferentiation hypothesis that discusses the modulation of smooth muscle cells (SMCs) from mature contractile cells to synthetic, secretory cells. According to this theory, once contractile SMCs are modulated, synthetic SMCs are thought to secrete collagen and may contribute to atherosclerosis. This hypothesis was accepted until a novel study published evidence for the existence of multipotent vascular stem cells (MVSCs). MVSCs were isolated from the tunica media of rat, transgenic mice with minimal investigation into human vascular tissue. Tang et al characterized MVSCs as having multipotent differentiation capability for neurons, Schwann cells, SMCs, osteoblasts, chondrocytes, and adipocytes. In the present study, human MVSC characterization was performed to validate their existence in human tissue. Seven MVSC samples from aortic arteries of aging persons and different stages of plaque progression from femoral arteries were characterized to create an expression profile and determine any differences in expression and differentiation capability. The results demonstrated all of the analyzed MVSCs express rodent associated transcription factors Soxl 0, Soxl 7 and intermediate filament proteins S 100~, neural filament polypeptide medium (NFM). Human MVSCs also uniformly expressed uninvestigated rodent markers: Slug, Desmin, Nestin and smooth muscle actin (SMA). Differentiation assays demonstrated all analyzed MVSCs have differentiation capability for mesodermal and ectodermal lineages. Representative samples from normal and plaque MVSCs were further characterized with flow cytometry and angiogenesis cytokine array analyses to provide supporting evidence for two mechanisms implicated in plaque progression, inflammation and angiogenesis. One normal MVSC sample and two different MVSC plaque samples expressed typical MSC surface markers: CD29, CD44, CD73, CD90 and CD105. One of the plaque samples contained a subpopulation of cells that expressed vascular cell adhesion molecule-I (VCAM-1) CD106 and chemokine receptor CD188, suggesting a role in inflammation. Data from an angiogenesis cytokine array demonstrated bone-like plaque MVSCs had higher levels of a plaque implicated cytokine, urokinase plasminogen activator (uPA) as compared to two normal MVSC samples. This supports the hypothesis that angiogenesis contributes to plaque progression. In conclusion this research demonstrated an expression profile of MVSCs by showing expression profiles and differentiation capability that was consistent among the seven analyzed MVSC samples.