pulmonary hypertension Archives - Amazing Health Advances

UCLA-Led Study Unveils New Insights and Potential Treatments for Pulmonary Hypertension

The AHA! Team — Mon, 21 Oct 2024 17:48:21 +0000

University of California, Los Angeles (UCLA), Health Sciences via Newswise – A new study from researchers with UCLA Health and collaborating organizations has found that asporin, a protein encoded by the ASPN gene, plays a protective role in pulmonary arterial hypertension (PAH). Their findings, which were published on August 21 in the peer-reviewed journal Circulation, offer new insights into this incurable, often-fatal disease and suggest potential new ways to treat it. “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 Dr. Jason Hong, a pulmonary and critical care physician at UCLA Health and the study’s corresponding author. “This novel finding opens up new avenues for understanding PAH pathobiology and developing potential therapies.” Pulmonary hypertension is a serious medical condition characterized by high blood pressure in the arteries that supply the lungs. It causes these arteries to narrow or become blocked, which, in turn, slows blood flow to the heart, requiring it to work harder to pump blood through the lungs. Eventually, the heart muscle becomes weak and begins to fail. Need for New Therapies According to recent estimates, PAH affects about 1% of the global population, but that number climbs to 10% in people who are 65 or older. There’s no cure for the disease, but medications and lifestyle changes can help slow progression, manage symptoms and prolong life. The urgent need for new therapies, combined with the potential of multiomics – an integrated approach to drive discovery across multiple levels of biology – inspired Hong and research colleagues, including co-first author Lejla Medzikovic and senior author Mansoureh Eghbali to take a deep dive into the disease. Both work at UCLA’s Eghbali Laboratory. Methodology For the study, the researchers applied novel computational methods, including transcriptomic profiling and deep phenotyping, to lung samples of 96 PAH patients and 52 control subjects without the condition from the largest multicenter PAH lung biobank available to-date. They integrated this data with clinical information, genome-wide association studies, graphic models of probabilities and multiomics analysis. “”Our detailed analysis found higher levels of asporin in the lungs and plasma of PAH patients, which were linked to less severe disease,” Hong said. Additionally, Medzikovic noted that their cell and living-organism experiments found that asporin inhibited pulmonary artery smooth muscle cell proliferation and a key signaling pathway that occurs with PAH. “We also demonstrated that recombinant asporin treatment reduced PAH severity in preclinical models,” said Medzikovic. Next Steps Hong and colleagues plan to further investigate the mechanisms by which asporin exerts its protective effects in PAH and explore potential therapeutic applications, focusing on how to translate their findings into clinical trials. “Asporin represents a promising new target for therapeutic intervention in pulmonary arterial hypertension,” he explained. “Enhancing asporin levels in PAH patients could potentially lead to improved clinical outcomes and reduced 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†. Legend: *Joint first authors; ‡ Joint second authors; †Joint last authors Funding: This work was supported by American Heart Association grant 23POST1022457 (L.M.), American Thoracic Society Early Career Investigator Award in Pulmonary Vascular Disease (J.H.), and U.S. NIH grants K08HL169982 (J.H.), R01HL147586 (M.E.), R01HL162124 (M.E.), R01HL159865 (M.E.), R01HL147883 (X.Y.), R24HL105333 (W.N. and M.P.), R01HL160941 (W.N., A.D., and M.P.), British Heart Foundation Senior Basic Science Fellowship FS/SBSRF/21/31025 (C.R.), and funding for the PHBI is provided by NHLBI R24HL123767 and by the Cardiovascular Medical Research and Education Fund (MAA). Disclosures: Drs. Medzikovic, Hong, and Eghbali are coinventors of US provisional patent application No. 63/544,027, “Asporin in Pulmonary Hypertension.” To read the original article click here.

The post UCLA-Led Study Unveils New Insights and Potential Treatments for Pulmonary Hypertension appeared first on Amazing Health Advances.

New Measure of Heart Function Could Improve Survival for People with Heart Failure

AHA Publisher — Thu, 17 Jun 2021 07:00:35 +0000

University of Virginia Health System via News-Medical – A new physiological measurement of heart function developed at UVA Health could improve survival for people with heart failure by identifying high-risk patients who require tailored treatments, a new study suggests. The study is the first to show a survival benefit from wireless pressure monitoring sensors implanted in the pulmonary arteries. Pulmonary artery proportional pulse pressure, or PAPP, is a new measure of heart function, developed at UVA, that can identify patients at very high risk of hospitalization or death from systolic heart failure or pulmonary hypertension (high blood pressure in the heart and lungs). Previous research by the researchers showed that patients with low PAPPs were at far greater risk than those with higher PAPPs, so the UVA researchers tested whether these benefits were maintained in patients undergoing implantation of pressure sensors that continuously monitor pressure in the pulmonary artery. “We found that PAPP is a very good measure of how stiff or compliant the pulmonary arteries are. The stiffness of the pulmonary arteries determines how much resistance the right side of the heart has overcome to pump blood effectively to the lungs. The importance of this simple measure is that it can identify patients that are at greatest risk of dying or being hospitalized. This allows us to tailor more aggressive treatments.” Sula Mazimba, MD, MPH, Heart Failure Expert, UVA Health and the University of Virginia School of Medicine Treating Heart Failure Heart failure is a condition where the heart fails to pump blood adequately through the body. It affects more than 6.5 million Americans and more than 26 million people around the world. It causes more than 1 million hospital admissions each year, and approximately half of patients die within five years of diagnosis. UVA’s new study evaluated the benefits of PAPP monitoring in patients with systolic heart failure, in which the heart’s left ventricle is weak, as well as those with pulmonary hypertension – high blood pressure in the arteries in the lungs and right side of the heart. To test whether PAPP monitoring could predict outcomes in these patients, Mazimba and his colleagues reviewed data from 550 participants in the CHAMPION clinical trial. In the trial, participants were randomized to receive an implantable, wireless heart monitor called the CardioMEMS HF System. Mazimba and his collaborators found that participants with a below-average PAPP had a significantly higher risk of hospitalization or death than those with higher PAPPs. Further, the monitoring offered significant benefit to those with low PAPPs, reducing the risk of death by 46% annually during two to three years of follow-up. “The implications of this study are highly significant,” said Kenneth Bilchick, MD, MS, a cardiologist at UVA Health and co-investigator on the study. “We now have identified a specific group of patients who appear to have a marked improvement in survival with implantation of these pulmonary artery wireless monitors. As a result, the findings of the study could maximize the impact of this technology for a large number of potential candidate patients. This is an excellent example of how secondary analyses of clinical databases maintained by the National Institutes of Health can result in novel and personalized approaches to patient care.” The UVA researchers say more study is needed to determine the full potential of PAPP monitoring to improve care for patients with heart failure, but they were encouraged by the early results. “In the past, the function of the right chamber of the heart was often ignored and considered to be inconsequential to the overall performance of the heart, but we are now learning that this is not the case,” Mazimba said. “Having tools that signal when the right side of the heart is under strain may aid clinicians to adopt timely tailored treatments for heart-failure patients.” Findings Published The researchers have published their findings in the scientific journal Heart, Lung and Circulation. The research team consisted of Mazimba, Greg Ginn, Hunter Mwansa, Olusola Laja, Christiana Jeukeng, Comfort Elumogo, Brandy Patterson, Jamie L .W. Kennedy, Nishaki Mehta, John A. Hossack, Alex M. Parker, Andrew Mihalek, Jose Tallaj, Nishtha Sodhi, Younghoon Kwon, Salpy V. Pamboukian, Philip B. Adamson and Bilchick. The CHAMPION Trial was funded CardioMEMS Inc, subsequently acquired by St Jude Medical and then Abbott. To read the original article click here.

The post New Measure of Heart Function Could Improve Survival for People with Heart Failure appeared first on Amazing Health Advances.