Cardiovascular disease is the leading cause of death in Canada. Atherosclerosis is a cardiovascular disease, in which the inside of blood vessels contain fatty growths known as plaques. Over time, these plaques become unstable and can break, resulting in blockage of blood vessels. This can lead to heart attacks, strokes and limb loss. Wendy Boivin’s research explores what makes a plaque develop, grow, and become less stable. She is focusing on a protein called Granzyme B, which is known to cause plaques. What is unknown is which of two possible approaches Granzyme B uses to induce plaque formation and atherosclerosis: either by entering blood vessel cells and killing them, or by breaking down structural proteins in the blood vessel. Wendy Boivin is studying the role of perforin, a protein that is required for Granzyme B to enter into blood vessel cells. By conducting a study that observes what happens when perforin is removed from blood vessels, she can pinpoint the pathway Granzyme B uses to cause atherosclerosis. Ultimately, this study may contribute to new therapeutic targets for combating this disease.
Research Location: St Paul's Hospital
The Role of Granzyme B in Aortic Aneurysms
An aneurysm is a permanent dilation, or ballooning, of a blood vessel or an artery to 1.5 times its normal diameter. It is usually a complication of atherosclerosis, a form of cardiovascular disease where the interior walls of blood vessels are blocked by a fatty substance called plaque. While most aneurysms are small, slow growing and rarely rupture, some are large, fast growing and at higher risk of rupturing. Aneurysm formation can result in hemorrhaging and death if not immediately repaired – the mortality rate after a rupture is 80-90 per cent. Aneurysms in the brain (cerebral aneurysms) can rupture and cause bleeding within the brain, resulting in a stroke. Ciara Chamberlain is studying a protease, Granzyme B, which is made and released by certain types of immune cells. Granzyme B may play a role in aortic aneurysms by breaking down structural proteins and causing thinning of the blood vessel wall. Building upon work in this area already conducted at the James Hogg iCAPTURE Centre, this research seeks to provide definitive evidence about the therapeutic potential for Granzyme B inhibition for the prevention of aneurysms in patients with mild or advanced atherosclerosis.
The Role of Ubiquitin/Proteasome System in Heart Failure
Heart failure is a disorder in which the heart loses its ability to pump blood efficiently. Despite recent advances in treatment, heart failure remains the leading cause of death in Canada. One in four Canadians suffers from heart disease, and more than 70,000 Canadians die from heart diseases each year. Treatment of heart failure is a major economic and social burden. The proteasome is a large multiprotein complex found in all cells, which breaks down unwanted or damaged proteins that have been “tagged” for elimination with a small protein called ubiquitin. The ubiquitin/proteasome system contributes to many cellular functions, including cell division, quality control of newly-produced proteins, and immune defense. Impairment of this system has been linked to several diseases, including cancer, Alzheimer’s and Parkinson’s diseases. It may also play a role in the development of heart failure. Tse Yuan Wong’s research is exploring the contribution of the ubiquitin/proteasome system to heart failure. This involves examining the functional changes of this system in heart failure and determining how it is regulated. He will also explore how disturbed proteasome function affects the progression of heart failure. This study will provide valuable insights into the mechanisms of heart failure, which could lead to novel therapeutic strategies that could have a huge impact on health care in Canada.
The heart as an immunologic organ: Cardiac myocytes in innate immunity
It’s well established that severe infection in critically ill patients can result in heart damage, but what causes this damage is unclear. One possibility is that heart muscle recognizes and responds to infectious pathogens and their products, triggering events within heart cells that ultimately lead to heart failure. Dr. John Boyd is researching the link between serious infection and cardiac dysfunction. The immune system uses Toll-like receptors to recognizes infectious products. Boyd aims to establish the role and function of Toll-like receptors in the heart, and what response occurs in heart muscle cells when incubated with infectious pathogens that are known to activate these receptors. Because Toll-like receptors also recognize and respond to tissue damage arising from ischemic heart disease (when there is a decrease in the blood supply to the heart caused by constriction or obstruction of the blood vessels) and heart transplant rejection, the research could have relevance beyond cardiac response to acute infection. Ultimately, Boyd aims to provide novel insights into the connection between the heart and immunity, which could lead to the development of new strategies to improve outcomes in diseases that involve inflammatory responses of the heart.
Estimating current and future direct medical costs associated with HIV/AIDS in British Columbia using an integrated model of clinical disease history and population transmission dynamics
HIV/AIDS continues to be a major health issue in Canada, twenty-five years after the first cases were reported. About 58,000 Canadians, including 13,000 BC residents, are infected with HIV (the human immunodeficiency virus that leads to AIDS), and the incidence appears to be rising. A rough estimate sets the medical costs of caring for people with HIV/AIDS at more than $800 million a year. But rapid treatment advances make medical costs a moving target. Karissa Johnston is using the computer simulation model she developed in her earlier MSFHR-funded research to more accurately estimate the annual and lifetime medical costs of treating people infected with HIV. Johnston has designed a series of modules to measure the amount of HIV virus in peoples’ bloodstream (called the viral load) over their lifetime, their initiation and adherence to antiretroviral medications, their use of health services, and their survival time with different treatment regimes. As new treatments or data become available, individual modules can be updated without affecting the others. This information can help health care providers assess the costs and effectiveness of different treatment options. For example, antiretroviral medications successfully suppress viral load, reducing the risk of passing the infection during a sexual encounter. Even though the medications are costly, this tool will show if they ultimately result in costs savings due to a reduction in new infections.
Interdisciplinary Team Generating Research on Complex Patients to Develop Innovative Solutions
This award funds the creation of a transdisciplinary team studying health issues of complex patient groups with multiple illnesses, and varied ethnicities and socio-economic backgrounds. The goal is to examine the health status and trajectory of these patients by integrating research about the social determinants that affect their health, such as education, housing status, and income level.
An Internet-based self monitoring intervention for patients with chronic heart failure
In 1997, congestive or chronic heart failure (CHF) was the primary cause of death in British Columbia and in 2000, it was the most common cause of hospitalization for Canadians over the age of 65. Multidisciplinary interventions, including education, follow up and self-management strategies have been shown to improve quality of life and decrease subsequent hospital admissions among people with CHF. However, up to 50 per cent of hospital readmissions for CHF occur because patients have not learned to manage and monitor their condition effectively. Biljana Maric’s research is investigating the feasibility of Internet-based self-monitoring for CHF patients. Participants will log on to the study website each morning, enter their current body weight and answer five questions about their health status and any symptoms they are experiencing. A nurse will log on to a secure database to monitor responses and follow up with participants when responses trigger an alert. Biljana’s study will examine patient and staff uptake, and assess the impact of the program on patient quality of life and self care. If adopted, Internet monitoring of heart patients could decrease the health care costs associated with heart failure readmissions, alleviating some of the financial burden on the health care system while improving patient health outcomes.
An Empirical Test of Rational Polydrug Addiction
The economic model of rational addiction was a breakthrough in the economic theory of consumption of addictive substances. This model’s aim is to reliably estimate an addict’s change in consumption of an addictive substance due to a change in the drug’s price or the price of another drug to which the individual is addicted. Polydrug abuse within populations of heroin addicts has been observed within health services research literature for some time. Suggestions have been made to target treatment interventions and outcome assessment to multiple drugs, rather than a single drug in clinical trials involving substance abusers. Despite this, relatively little epidemiological research has been carried out to evaluate the effectiveness of different modes of treatment for drug abuse in polydrug addicts. Bohdan Nosyk is researching whether individuals addicted to more than one substance (e.g. heroin and cocaine) display some association in their consumption patterns of these substances. If there is a significant association in consumption, focusing treatment on one addiction may be ineffective given the increase in consumption within the other (untreated) drug addiction. This study will survey individuals addicted to multiple drugs residing in Vancouver’s Downtown Eastside to determine the relationship between illicit drug prices and consumption. Research into the addicted illicit drug consumer’s behaviour – in particular, how the consumer substitutes between substances and which drugs tend to complement one another – will provide policy-makers with evidence on which to base future directions in the treatment for addictive substance abuse.
British Columbia Transient Ischemic Attack Project
A transient ischemic attack (TIA) occurs when there is a temporary disruption of blood supply to the brain. Damage from a TIA is temporary and reversible, but the experience is an important warning symptom for stroke, which is a major cause of death and long-term disability. Patients have a five to ten per cent risk of having a stroke within a week of a transient ischemic attack. Patients with TIA symptoms often go to the emergency department for evaluation, but there is no universally accepted strategy for managing TIA in B.C. Emergency Departments (EDs). A major challenge has been the lack of a system for determining which patients are at high risk for having a stroke and warrant urgent investigation and treatment. Dr. Devin Harris is evaluating the effectiveness of a clinical guideline for standardizing TIA care in EDs. This evidence-based guideline is being implemented as a pilot project in six B.C. emergency departments and will then be expanded to all 92 EDs in the province. Devin is examining physician adherence to the guideline and the impact on patient outcomes. This information will be used to develop a model for predicting which patients are at high risk of stroke after TIA, leading to better preventive and treatment options.
Why are women at increased risk of chronic obstructive pulmonary disease and lung cancer? Is inflammation the missing link?
Chronic obstructive pulmonary disease (COPD) is a term for a group of respiratory diseases—such as chronic bronchitis or emphysema—in which there is chronic obstruction of airflow through the airways and lung damage. In Canada, despite the fact that more men smoke than women, the rates of chronic COPD and lung cancer in women are expected to exceed those in men within the next five years. Dr. Donald Sin is investigating why women seem more susceptible than men to COPD and lung cancer. His research proposes that women mount a more vigorous inflammatory reaction to cigarette smoke and environmental irritants than men, resulting in chronic lung and systemic inflammation that can lead to COPD and in some cases, lung cancer. Dr. Sin is comparing sex-related differences in the relationship between lung and systemic inflammation and the development of lung cancer. His research will not only shed light on why women are more susceptible to COPD and lung cancer compared to men, but may also be an important foundation for developing medications to reduce the risk.