Minimally Invasive Endoarterial Biopsy Can Unlock Complex Molecular Mechanisms of PH Development

Alice Melão, MSc avatar

by Alice Melão, MSc |

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Collecting tissue samples from vessels damaged by pulmonary hypertension (PH) can help scientists learn about molecular mechanisms that cause the disease, as well as which may help in its treatment, according to a new study.

The study, “Assessment of microRNA and gene dysregulaton in pulmonary hypertension by endoarterial biopsy,” appeared in the journal Pulmonary Circulation It describes how a minimally invasive cardiovascular catheter to collect affected arterial tissue — an endoarterial biopsy — allowed researchers to identify several small RNA molecules (miRNAs) that control PH-associated genes, in a porcine model of PH.

Endoarterial biopsies offer a way for researchers to obtain vascular tissue samples safely. They provide enough biological material to perform studies that could offer more insights into disease development and progression, as well as stage-specific genetic and protein variations.

Scientists still don’t really understand the vascular remodeling process that takes place during PH development. They have identified some proteins and components, such as endothelin-1, nitric oxide and prostacyclin, that form part of the process, but do not know the full extent of their purpose and activity.

Taking advantage of endoarterial biopsies, researchers identified 73 deregulated miRNAs upon PH-induced vascular remodeling. These miRNAS were found to regulate from one to 113 PH-associated genes, suggesting that they control several molecular pathways and biological processes that are dysregulated in PH.

“Measuring miRNA (and other molecular) changes directly in individual patients at specific stages of their disease process offers great promise for advancing knowledge of the molecular mechanisms and designing specific personalized therapy,” Abraham Rothman, a University of Nevada professor of medicine and the study’s first author, said in a press release.

Because the porcine PH model may not completely represent what happens in humans, the miRNAs identified in the study may or may not have a direct relevance to human PH. Nevertheless, the findings support the hypothesis that miRNAs are crucial to the complex molecular mechanism involved in PH.

Although further studies are needed, miRNA mimetic or antagonist therapy may have potential application in human PH.

“Endoarterial biopsy provides an innovative method to assess miRNA, gene, and other molecular regulation in normal and hypertensive pulmonary arteries at specific stages of the disease and opens a new window for precision therapy” said David Mann, CEO of Vascular BioSciences and senior author of the study.