Protection where it matters most for PAH patients

A group of unrecognizable scientists joining hands in solidarity in a laboratory.

Researchers from UCLA Health have discovered asporin (ASPN), a protein coding gene, to have an unexpected protective impact in pulmonary arterial hypertension (PAH). 

“We were surprised to find that asporin, which previously had not been linked to PAH, gets upregulated to increased levels as a response to counteract this disease process,” said corresponding author Jason Hong, MD, PhD, a pulmonary and critical care physician at UCLA Health. “This novel finding opens up new avenues for understanding PAH pathobiology and developing potential therapies.”

Jason Hong, MD, PhDJason Hong, MD, PhDUCLA HealthFor the study, which was published in Circulation, a journal of the American Heart Association, Dr. Hong collaborated with colleagues at UCLA’s Eghbali Laboratory, namely co-first author Lejla Medzikovic, PhD, and senior author Mansoureh Eghbali, PhD. 

Currently, PAH is incurable, but certain medications and lifestyle modifications can help manage symptoms, slow disease progression and prolong life. Dr. Hong and team were motivated by the urgent need for new PAH therapies and the exciting potential of multiomics — an integrated methodology that combines multiple levels (omes) of biology to drive discovery.

The researchers created a novel computational approach, using deep phenotyping and transcriptomic profiling, that was applied to the lung samples of 96 patients with PAH and 52 healthy control subjects. The data, which came from the largest multicenter PAH lung biobank, was then integrated with clinical information, multiomics analysis, graphic models of probabilities and genome-wide association studies. 

“Our detailed analysis found higher levels of asporin in the lungs of plasma and PAH patients, which were linked to less severe disease,” Dr. Hong said in a UCLA Health news release. 

In additional cell and living organism experiments, the researchers found that asporin hinders smooth muscle cell proliferation in the pulmonary artery as well as a key signaling pathway indicative of PAH.

“We also demonstrated that recombinant asporin treatment reduced PAH severity in preclinical models,” Dr. Medzikovic said.

According to the team, further research is required to examine the shielding effects of asporin in PAH and translate these findings into clinical trials, with the goal to identify new therapeutic applications. 

“Asporin represents a promising new target for therapeutic intervention in pulmonary arterial hypertension,” said Dr. Hong. “Enhancing asporin levels in PAH patients could potentially lead to improved clinical outcomes and reduced disease progression.”  

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