Pulmonary arterial hypertension (PAH) is a devastating disorder with a poor prognosis and no cure. Recent research has produced a number of useful therapies, however, and rapid progress in basic research is pointing to promising therapeutic strategies.
PAH occurs when small arteries in the lung narrow, leading to elevated blood pressure in the pulmonary artery. Such pressure overloads the right ventricle of the heart, weakening the chamber. Eventually, such patients develop right heart failure.
Diagnosis of PAH is often delayed. "Idiopathic pulmonary arterial hypertension usually occurs in younger individuals who present with nonspecific symptoms, such as shortness of breath with exertion," says Teresa De Marco, M.D., professor of medicine and director of the Heart Failure and Pulmonary Hypertension Program at UCSF. "These symptoms are often ascribed to asthma, deconditioning, anxiety or other ailments."
An echocardiogram is the best screening tool available for diagnosing PAH, but the electrocardiogram or chest radiograph can lead a physician with a high index of suspicion down the right path. "It is imperative that we raise awareness of PAH in order to promote early diagnosis, referral and treatment," De Marco says.
The UCSF Pulmonary Hypertension Program has been designated a center of excellence for the evaluation and treatment of the disorder. "At UCSF, we are proud that our PH program involves a well-rounded team of physicians, nurses, social workers and researchers, allowing us to deliver state-of-the-art care to our patients," says Dana McGlothlin, M.D., assistant clinical professor of medicine and associate medical director of the Pulmonary Hypertension Program.
UCSF has participated in many of the pivotal trials for new therapies. "We can offer the full range of care, including conventional and experimental therapies, as well as lung transplantation," De Marco says.
Although current therapies have come a long way since the 1980s, they have significant limitations and are costly. "Hope for new and better therapies is coming from basic research elucidating the pathogenesis and pathobiology of the disease," De Marco says.
An understanding of the vascular derangements that occur in PAH will result in the development of newer drugs that promote dilation of the pulmonary arterial tree. Furthermore, a new understanding of the growth factors that encourage cell replication in the walls of vascular tissue may lead to drugs that block that cell growth and thereby slow the narrowing of the arteries.
De Marco says that, in collaboration with John Kane, M.D., Ph.D, professor of medicine and an investigator in the UCSF Cardiovascular Research Institute, "we are creating a DNA databank of patients with pulmonary hypertension, which is linked to a clinical database. This will allow us to identify candidate genes that may predispose individuals to the development of PAH," De Marco says.
Other research at UCSF includes efforts to elucidate the effect of overactivity of the enzyme arginase in PAH, and to understand the activity of stem cells in the progression of the disease. Researchers collaborating with Yerem Yeghiazarians, M.D., director of UCSF's Cardiac Stem Cell Translational Development Program, are investigating the possibility of transfecting stem cells (endothelial progenitor cells) with genes that are important in vasodilation or inhibition of cell growth.
"Our new understanding of the pathobiology of vascular remodeling is leading to ideas for novel therapeutic strategies," De Marco says.
To contact Dr. Teresa De Marco, call (415) 476-3117.
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