Project 170939
Understanding the activation and the roles of the IKK complex-NF-kappaB signaling cascade in the inflammatory and hypertrophic actions of Angiotensin II in vitro and in vivo
Understanding the activation and the roles of the IKK complex-NF-kappaB signaling cascade in the inflammatory and hypertrophic actions of Angiotensin II in vitro and in vivo
Project Information
| Study Type: | Other Mechanistic_Study |
| Therapeutic Area: | Oncology |
| Research Theme: | Biomedical |
| Disease Area: | cancer |
| Data Type: | Canadian |
Institution & Funding
| Principal Investigator(s): | Servant, Marc |
| Institution: | Université de Montréal |
| CIHR Institute: | Circulatory and Respiratory Health |
| Program: | |
| Peer Review Committee: | Cardiovascular System - C: Vascular System |
| Competition Year: | 2008 |
| Term: | 5 yrs 0 mth |
Abstract Summary
Cardiovascular disease (CVD), including heart disease, stroke and peripheral vascular disease, is the leading cause of death in Canada and in Western society. When death is not the end point, CVD jeopardized the quality of life. CVD is also the leading cause of hospital admissions and despite progress in its prevention, detection, and treatment, which exact an enormous toll in Canada (billions of dollar each year), it will still kill thousand of Canadian this year. Several risk factors for coronary artery disease (CAD) have been well documented including gender, age, hyperlipidemia, hypertension, smoking, diabetes, family history, physical inactivity, overweight and excessive alcohol. However these factors explain only part of attributable CVD, and other factors must be involved. Indeed, a growing body of evidence supports the concept that local and systemic chronic inflammation may play a role in the initiation and progression of atherosclerosis and its complication (angina crisis, stroke and sudden death). In the arteries, atherosclerosis is characterized by a recruitment of cells of the immune system into the vessel wall, an accumulation of circulating cholesterol followed by an increase in the number of vascular muscle cells, the major component of the vascular system. These processes lead ultimately to plaque formation, which diminish blood flow and ultimately leads to myocardial infarction or stroke. The underlying cause of this chronic inflammation and how its specifically relates to CAD is at the moment unknown. Evidence suggests however that a hormone, angiotensin II (Ang II) known to increase the blood pressure, might be an important contributor to this chronic inflammation of the vessel wall leading to atherosclerosis. Thus, the principal objective of my research proposal is to characterize which molecular signals are induced by Ang II and important for its inflammatory effect. Results generated by this project will help to discover new therapeutic target
Research Characteristics
This project includes the following research characteristics:
Study Justification
"Our research program is focused on identifying genes that are critical for the survival of cancer cells but dispensable for normal cells."
Novelty Statement
"The ultimate goal of this research is to contribute to a better understanding of how the loss of tissue architecture contributes to cancer, and to identify new avenues for therapeutic intervention."
Methodology Innovation
using genetic screens to identify novel therapeutic targets in cancer cells