Research

PULMONARY ARTERIAL HYPERTENSION

Pulmonary arterial hypertension (PAH) is high blood pressure (hypertension) within the lung (pulmonary) arterial circulation.  It is a disease that results in narrowing and blockage of the very smallest arteries (blood vessels) throughout the lungs. The blood vessels that are affected are about the size of a human hair. While small there are an enormous number of these vessels that in total manage nearly all of the blood that travels through the lungs.  These small vessels are thus very important because nearly all of the blood in the circulation must pass through them. As these blood vessels become blocked, the pressure in the pulmonary arterial circulation increases which puts a strain on the right side of the heart.  Ultimately, the pressure may increase to a point that blood cannot flow normally through the lungs. When this happens, in addition to putting a strain on the right side of the heart, blood flow to the rest of the body is inadequate. 

Normal:     PAH:      

PAH can occur in association with several other diseases such as autoimmune diseases, but often no cause is found. If PAH patients have a family history of PAH or have a mutation detected in a gene known to cause PAH, they may have heritable PAH (HPAH). If there are no other causes and no known family history, PAH is called idiopathic (IPAH). The incidence of IPAH in the general population is about 1-2 per million. The incidence of HPAH appears to be much lower. 

IPAH and HPAH look virtually identical to one another in all respects.  Symptoms, clinical course, and response to therapy are equal, except that HPAH may be diagnosed about 10 years earlier than IPAH.  HPAH can be inherited from a male or female parent. The incidence is 2.4:1 females to males, similar to the general IPAH population. HPAH is inherited as a dominant trait, although, many persons who carry the gene do not get the disease. A gene that causes HPAH, bone morphogenetic protein receptor 2 (BMPR2) was discovered and described in 2000 by Vanderbilt University and Columbia University researchers, independently. This gene is associated with cell growth and development, as well as other cellular processes. Rare variations in the composition of this gene (also known as mutations) may lead to the formation of abnormal pulmonary arteries seen in this disease, although the precise mechanisms remain unclear. The familial form of this disease has long been an interest of the Vanderbilt group, although we do study many forms of the disease in depth including IPAH.  Occasionally, patients with IPAH are found to have mutations in this gene as well, and we thus know that those patients have heritable disease that can be passed to their children (HPAH) despite no known family history of PAH.

Common symptoms of the pulmonary hypertension and reduced blood flow are passing out, shortness of breath with exercise, blue lips and fingers, and swelling of the ankles and legs. PAH can develop in men or women at any age, but is more common in women. The age of diagnosis does vary according to type.  For those with HPAH and IPAH, diagnosis is most common between the ages of 20 and 40 years, although for those with many other types of PAH associated with other diseases such as autoimmune disease the age at diagnosis is 10-15 years older.  PAH may progress silently for many years, and thus often takes a long time before diagnosis is made. Many patients in the early stages of PAH have mild symptoms, and believe they are just overweight, growing older, or out of shape. Even when a patient has significant symptoms, he or she may see a doctor several times before the doctor thinks about PAH, because it is an uncommon disease and many doctors will not have seen a patient who has PAH.

Exciting research in this disease at our Center has been advanced through several funding grants from the National Institutes of Health (NIH) and other funding agencies.  In particular, we have a NIH grant titled “Hormonal, Metabolic, and Signaling Interaction in PAH” which began September, 2012 and will continue until July, 2017.  This large program grant supports a number of human, animal model, and cell-based studies which we hope will translate into novel information and therapeutics for PAH. 

HISTORY AND CURRENT STUDIES:

Our genetic studies for HPAH have been supported for the majority of the past 20 years by the National Institutes of Health. Our Vanderbilt Family Registry was initiated in 1994. The purpose of the registry is to find and enroll as many families with HPAH as possible. The more families that are enrolled the more information will become available concerning the disease. Any personal or medical data submitted is kept strictly confidential.

Our current studies: Click some of the links below to see what research we are conducting and how you might can contribute!

Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension

Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension

MobileHealth Intervention in PH 

Clinical and Mechanistic Understanding of Right Ventricular Steatosis in Pulmonary Arterial Hypertension

Risk and Resilience in Pulmonary Arterial Hypertension and Genetically Susceptible Individuals

Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension (T3PAH)

Research participants are protected by a Certificate of Confidentiality from the Department of Health and Human Services. The Certificate prevents researchers from being forced to expose any information concerning subjects in their study. The major goals of the study are to understand the processes that cause the disease, attempt to develop new treatments, and provide information to patients and physicians.

For more information contact:

PULMONARY ARTERIAL HYPERTENSION STUDY

Anna Hemnes, MD Co-Director and Evan Brittain, MD Co-Director

Thomas Strayer, PhD Program Manager

P: 1-615-936-0156 FAX 1-615-322-1372

Thomas.e.strayer@vumc.org

GENETIC TESTING:

How can I get genetic testing for IPAH/HPAH?