Role of cigarette smoke and hypoxia in the development of pulmonary hypertension
What is pulmonary hypertension?
Pulmonary hypertension is raised blood pressure within the pulmonary arteries, which are the blood vessels that supply the lungs. In a healthy person, blood travels through the pulmonary arteries from the right-hand side of the heart, picking up oxygen when it reaches the lungs.
The oxygen-rich blood then returns to the left-hand side of the heart and is pumped around the body to supply oxygen. However, if you have pulmonary hypertension, the walls of your pulmonary arteries are thick and stiff, making it difficult for them to expand to allow more blood through.
The reduced blood flow makes it difficult for the right-hand side of your heart to pump blood through the arteries, which means this part of the heart has to work harder. If the right-hand side of your heart has to continually work harder, it may gradually become weaker. This makes it less efficient at pumping blood and can lead to heart failure. Therefore pulmonary hypertension is a serious medical condition.
Cigarette smoke, hypoxia and pulmonary hypertension
There can be many different causes for the changes to your arteries. Chronic Obstructive Pulmonary Disease (COPD)–a term that describes a number of lung diseases that affect breathing, is a common condition and the second most frequent cause of pulmonary hypertension, with up to 50% patients with advanced COPD affected. Pulmonary hypertension in COPD contributes prominently to increased mortality, morbidity and use of health-care resources. However, the development of pulmonary hypertension in COPD is not fully understood. Cigarette smoke is the most common cause of COPD and patients with COPD develop hypoxia (lack of oxygen) frequently.
New evidence suggests that cigarette smoke can directly cause pulmonary artery wall thick and stiff, which can then be further enhanced by hypoxia, but the reasons are unclear.
Treatment for pulmonary hypertension in COPD
Although there are drugs that are commonly used for treatment of pulmonary hypertension caused by other conditions, these drugs are not recommended for pulmonary hypertension in COPD, because so far there is no proven benefit. So there is a need for new therapies.
Our research plan
The increase in numbers (proliferation) of a particular cell type, pulmonary artery smooth muscle cells, contributes most to pulmonary artery wall thickness and stiffness.
In this project, we plan to recreate pulmonary artery wall thickness and stiffness by studying the effect of cigarette smoke and hypoxia, individually and in combination, on the increase in the numbers of these cells.
With our pilot data, we anticipate that cigarette smoke and hypoxia both may cause an increase of chemicals that promote muscle cell proliferation and a decrease of chemicals that inhibit the proliferation, and this imbalance then leads to a net increase of muscle cell number, contributing to pulmonary artery wall thickness and stiffness. The effect is further enhanced when smoke and hypoxia are combined.
This imbalance may be due to cigarette smoke-caused dysfunction of genes that control the production of these chemicals. We will test the effect of drugs that can maintain the normal functions of genes to of these genes to assess if they can restore the balance and prevent cigarette smoke-caused muscle cell proliferation.
In addition to the cell study, we will also compare human lung tissue samples from people with or without COPD and people who are smokers and non-smokers, to find out if cigarette smoke causes dysfunction of these genes in human lungs.
We hope the outcome of the project will help us to understand the role of cigarette smoke and hypoxia in the development of pulmonary hypertension in COPD and to identify new therapeutic targets for the development of new drugs to benefit patients in the near future.
Researcher Professor Linhua Pang