A laboratory at the University of Kansas Medical Center is working to understand the mechanisms of pulmonary arterial hypertension (PAH) in HIV patients. This fundamental research uncovered several clues that could help identify future therapies for PAH.
About 1 in 200 AIDS patients will develop HIV-related pulmonary arterial hypertension (HIV-PAH), and most will die very quickly from it. That occurrence is nearly 1,000 times greater than that of the general population. The majority of HIV-PAH occurs in those with a history of intravenous drug use.
Multiple investigators have established the role of HIV in the pathogenesis of PAH and a relationship between PAH and exposure to drugs of abuse. We also know that patients who use drugs such as cocaine, opioids and methamphetamines are at increased risk for HIV infection. Our laboratory has considered these independent risk factors and extensively investigated the potential link between HIV-associated PAH and intravenous drug use. Our research is aimed at understanding mechanistically how HIV-1 and drugs of abuse contribute alone and in concert with the vascular dysfunction associated with PAH.
The salient finding in our reports is the synergistic or additive increase in the damage seen in pulmonary vascular cell types: smooth muscle and endothelial cells on simultaneous exposure to HIV-1 and illicit drugs. Current research is focused on:
- Elucidating the role of nocoding RNAs in the regulation of proliferative and antiproliferative cascades in the pulmonary smooth muscle cells
- Defining the role of autophagy/mitophagy in the shift of early cell-death phase of pulmonary endothelium to the later proliferative/survival phase associated with angio-obliteration
- Investigating the role of extracellular vesicles derived from HIV-infected inflammatory cells in pulmonary vascular damage
Finding a cure for PAH is a major challenge. One thing we can do now is work to identify it earlier in the disease process. Symptomatic patients may present with dyspnea upon minimal exertion and edema of the lower extremities. Other symptoms include syncope, chest pain and nonproductive cough. Depending on the severity, however, patients may be asymptomatic. HIV patients with these symptoms – especially if they have a history of drug abuse – should be investigated thoroughly with transthoracic echocardiogram or the gold standard, right-heart catheterization.
The survival of patients with HIV-PAH is significantly low with available PAH therapies. Our hope is that understanding more about its pathogenesis will influence the development of novel therapies and biomarkers that will assist clinicians in treating these patients much more effectively in the future.
To consult with a physician or refer a patient, call 913-588-5862 or 877-588-5862.