Role of ron receptor tyrosine kinase in atherosclerotic plaque composition

Open Access
Henry, Staci Lynn
Area of Honors:
Bachelor of Science
Document Type:
Thesis Supervisors:
  • Pamela Hankey, Thesis Supervisor
  • Bernhard Luscher, Honors Advisor
  • atherosclerosis
  • inflammation
  • macrophage
  • Ron
  • apoptosis
  • collagen
  • necrosis
Atherosclerosis is a chronic inflammatory disease the progression of which is mediated, in large part, by the balance of macrophages within the lesions. The progression of atherosclerosis is associated with an increase in infiltrating inflammatory macrophages (also called M1 macrophages) and a decrease in tissue-resident macrophages linked to healing and cell clearance (also called M2 macrophages). Ron is a receptor tyrosine kinase expressed on tissue-resident macrophages. In vitro and in vivo, Ron promotes the development of macrophages linked to wound repair and apoptotic cell clearance and inhibits the activation of inflammatory macrophages. Therefore, we hypothesized that Ron would play a protective role in the progression of atherosclerosis. In order to test this hypothesis, we examined the composition of atherosclerotic plaques formed in the aortic roots of eighteen-week-old mice in the presence and absence of Ron. We examined the deposition of collagen, the percentage of apoptotic cells, and the extent of necrosis using trichrome collagen staining and TUNEL assay. The results showed a significantly greater percentage of apoptotic cells present in plaques of mice in the presence of Ron, associated with a trend towards decreased necrosis in these plaques. However, we did not observe a significant difference in the amount of collagen deposition in the plaques from wild-type and Ron knockout animals. These data suggest that Ron may play a protective role in the progression of lesion formation, but may not protect against lesion rupture caused by decreased collagen in the fibrous cap.