Distinguishing the Role of the c-myb Proto-Oncogene in Mouse Models of Cardiovascular Disease

Despite considerable advances in our understanding of disease processes, cardiovascular diseases remain the top cause of mortality and morbidity in society today. Investigating the molecular and cellular mechanisms involved in the pathogenesis of these diseases to discover new therapeutic targets is of utmost importance. While much is known about the specific roles of transcription factor c-myb in leukocytes, comparatively little is known about c-myb in the context of cardiovascular disease. c-myb regulates vascular smooth muscle cell (VSMC) differentiation from embryonic stem cells, as well as the proliferation of mature VSMCs. The literature points toward several areas of opportunity to examine the role of c-myb in cardiovascular biology: first, to examine the role of c-myb in the regulation of adult vessel-resident VSMC progenitor cell proliferation and differentiation in response to vessel injury and the molecular mechanisms involved in c-myb-mediated VSMC differentiation. Second, while transgenic models manipulating c-myb have yielded significant insight in regards to homeostasis of the immune system, little is known about a role for c-myb in the regulation of baseline function of the cardiovascular system. While c-myb regulates VSMC differentiation and pathological VSMC proliferation, it is not known if it regulates VSMC contractile function and vascular contractility, and more generally, blood pressure homeostasis. Lastly, this dissertation examines the involvement of c-myb in experimental atherosclerosis, a disease model involving both leukocytes and vessel-resident cells such as VSMCs. Therefore, work of this dissertation aims to elucidate the role of c-myb in these areas and thus further the collective understanding of the mechanisms involved in cardiovascular pathophysiology.

Department dc:contributor.department

Laboratory Medicine and Pathobiology

Year dc:date.issued

2016

Author dc:creator

• Shikatani, Eric Akihiko

Advisor dc:contributor.advisor

• Husain, Mansoor

• atherosclerosis
• blood pressure
• c-myb
• differentiation
• progenitor cells
• restenosis

Handle dc:identifier.uri

http://hdl.handle.net/1807/76834

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/76834