A recent investigation conducted by researchers at UCLA Health and their partners has revealed that asporin, a protein linked to the ASPN gene, serves a protective function in pulmonary arterial hypertension (PAH).
The study, which was published on August 21 in the peer-reviewed journal Circulation, provides new perspectives on this serious and often fatal illness, hinting at possible innovative treatment methods.
“We were surprised to discover that asporin, which had not been associated with PAH before, is increased in response to help mitigate this disease,” remarked Dr. Jason Hong, a pulmonary and critical care physician at UCLA Health and the study’s lead author. “This groundbreaking discovery paves the way for better understanding of the disease mechanisms behind PAH and for the development of new treatments.”
Pulmonary hypertension is a critical health issue defined by elevated blood pressure in the arteries that lead to the lungs. This condition results in the narrowing or blockage of these arteries, impeding blood flow to the heart, forcing it to exert more effort to circulate blood through the lungs. Over time, this strain can weaken the heart muscle eventually resulting in heart failure.
Importance of New Treatments
Current estimates suggest that approximately 1% of the global population suffers from PAH, a statistic that rises to 10% among individuals aged 65 and older.
While no cure exists for this condition, some medications and lifestyle adjustments may help slow down its progression, alleviate symptoms, and extend life expectancy.
The pressing demand for new treatment methods, coupled with the possibilities offered by multiomics—a comprehensive approach to explore numerous biological levels—motivated Hong and his team of researchers, including co-first author Lejla Medzikovic and senior author Mansoureh Eghbali, to extensively investigate the disease. Both are associated with UCLA’s Eghbali Laboratory.
Research Methodology
In their research, scientists utilized innovative computational techniques, including transcriptomic profiling and deep phenotyping, to analyze lung samples from 96 PAH patients and 52 control subjects without the disease, sourced from the largest multicenter PAH lung biobank to date. This data was combined with clinical information, genome-wide association studies, probability models, and multiomics analysis.
“Our in-depth analysis showed elevated levels of asporin in the lungs and plasma of PAH patients, which were associated with milder disease symptoms,” stated Hong.
Furthermore, Medzikovic highlighted that experiments with cells and living organisms demonstrated that asporin curbs the proliferation of smooth muscle cells in the pulmonary artery and a critical signaling pathway influenced by PAH.
“We also showed that treating with recombinant asporin mitigated PAH severity in preclinical models,” added Medzikovic.
Future Directions
Hong and his team intend to further explore how asporin exerts its protective properties in PAH and look into its potential therapeutic uses, aiming to translate their discoveries into clinical trials.
“Asporin is emerging as a promising target for treatment strategies in pulmonary arterial hypertension,” he elaborated. “Raising asporin levels in PAH patients could lead to better health outcomes and a slowdown in disease progression.”
Authors: Jason Hong, MD, PhD,* Lejla Medzikovic, PhD*, Wasila Sun, BS‡, Brenda Wong, BA‡, Gregoire Ruffenach, PhD, Christopher J. Rhodes, PhD, Adam Brownstein, MD, Lloyd L. Liang, MS, Laila Aryan, PhD, Min Li, PhD, Arjun Vadgama, Zeyneb Kurt, PhD, Tae-Hwi Schwantes-An, PhD, Elizabeth A. Mickler, MS, Stefan Graf, PhD, Melanie Eyries, PhD, Katie A. Lutz, BS, Michael W. Pauciulo, MBA, Richard C. Trembath, MD, Frederic Perros, PhD, David Montani, MD, PhD, Nicholas W. Morrell, MD, Florent Soubrier, MD, PhD, Martin R. Wilkins, MD, William C. Nichols, PhD, Micheala A. Aldred, PhD, Ankit A. Desai, MD, David-Alexandre Tregouet, PhD, Soban Umar, MD, PhD, Rajan Saggar, MD, Richard Channick, MD, Rubin M. Tuder, MD, Mark W. Geraci, MD, Robert S. Stearman, PhD†, Xia Yang, PhD†, and senior author, Mansoureh Eghbali, PhD†. Note: *Joint first authors; ‡ Joint second authors; †Joint last authors
Funding: This research was supported by American Heart Association grant 23POST1022457 (L.M.), American Thoracic Society Early Career Investigator Award in Pulmonary Vascular Disease (J.H.), and multiple U.S. NIH grants, among others.
