Translational Science Oral Session I: Pulmonary, Critical Care, Cardiology, and Renal

Tuesday, April 15, 2025
3:30 pm - 4:45 pm

ADDITION OF PATHOLOGIC FLOW TO HEMIN-TREATED PULMONARY ARTERY ENDOTHELIAL CELLS IMPLICATES DISTINCT TRANSCRIPTOMIC PATTERNS IN SICKLE CELL DISEASE ASSOCIATED PULMONARY HYPERTENSION (Pulmonary / Critical Care)
Kelsey Holbert, MD, University of Illinois Chicago
Although the pulmonary vasculature is exposed to constant flow, most in-vitro work studying the mechanisms of pulmonary hypertension (PH) is performed under static conditions. The effects of pathologic flow have been studied in other vascular conditions such as systemic hypertension and atherosclerosis, but less so in diseases that affect the pulmonary vasculature. Flow may be particularly important in mechanisms of sickle cell disease (SCD) associated PH, where anemia and other physiologic stressors cause high cardiac output exposing the pulmonary vasculature to pathologic flow. Our previous work has implicated intravascular hemolysis and hemin release in the development of SCD-PH through pulmonary artery endothelial cell (PAEC) phenotypic transition and dysfunction. We hypothesize that PAEC exposed to flow, in addition to hemin, will demonstrate novel transcriptomic patterns that identify unique, clinically relevant processes related to the development of SCD-PH.

MITOCHONDRIAL METABOLIC REGULATOR PYRUVATE DEHYDROGENASE KINASE 4 (PDK4) MEDIATES SEX-SPECIFIC CARDIAC RESPONSE TO ENDOTOXEMIA (Cardiology / Cardiovascular Disease)
John Q. Yap, PhD, Loyola University Chicago
Sepsis is a life-threatening condition that occurs when the immune system is unable to properly respond to infection. Patients with sepsis often experience cardiomyopathy, which is characterized by cardiac inflammation, ventricle dilation and decreased cardiac function. Interestingly, females tend to have better cardiac outcomes during sepsis compared to males. In this study, we show that differential cardiac expression of pyruvate dehydrogenase kinase 4 (PDK4) in males and females contributes to sex-specific cardiac outcomes during sepsis. PDK4 is a mitochondrial protein that decreases glucose metabolism by inhibiting pyruvate dehydrogenase (PDH) and plays a critical role in energy production and substrate utilization in the heart.

SPATIAL TRANSCRIPTOMICS INSIGHTS ACROSS A SPECTRUM OF AIRWAY DISEASES (Pulmonary / Critical Care)
Ghandi F. Hassan, MD, Washington University in St Louis
In recent years, advanced multi-omics techniques have been used to profile genetic, transcriptional, and proteomic features in pulmonary disease. However, the lack of spatial resolution has limited our ability to distinguish variations in the airway niche that may provide new insights into pathogenesis. Spatial transcriptomic analysis platforms are powerful tools to bridge this gap, enabling the mapping of gene expression and cellular interaction networks with high spatial fidelity. These approaches have yet to be employed in a cross-sectional analysis of human airway disease.

THE IMMUNE LANDSCAPE OF INTRATHORACIC LYMPH NODES IS ASSOCIATED WITH THE LYMPHOPENIC IMMUNOTYPE IN SARCOIDOSIS (Pulmonary / Critical Care)
Christian Ascoli, MD, Department of Medicine; Division of Pulmonary, Critical Care, Sleep, and Allergy at the University of Illinois at Chicago

 

The presence of paradoxical peripheral lymphopenia defines a unique but poorly understood sarcoidosis immunotype associated with greater inflammatory activity and more severe organ involvement. Conventionally, lymphopenia is thought to result from increased numbers and heightened antiproliferative effects of CD4+ T regulatory cells on effector T-cells. However, it is recognized that the differentiation of naïve T-cells into different effector T-cell subsets depends on interactions with professional antigen-presenting cells (namely dendritic cells [DCs]) within the lymph nodes (LNs). Moreover, we and others have previously implicated aberrant innate-adaptive immune cell crosstalk as a determinant of lymphopenia in sarcoidosis, and recently, HLA-DRB1 alleles have been associated with lymphopenia. Thus, we hypothesize that interactions between DCs and lymphocytes within intrathoracic LNs determine distinct transcriptional programming that governs lymphocyte function and fate in sarcoidosis.

 

  THE EFFECT OF NICOTINE DELIVERY SYSTEM ON EXTRACELLULAR MATRIX BLOOD PROTEASE LEVELS: A RANDOMIZED CROSSOVER DESIGN (Pulmonary / Critical Care)

Ava Wilson, PhD, MSPH, Kansas University Medical Center

 

Recently, E-cigarettes and heated tobacco products (HTPs) have been marketed as combustible cigarette alternatives due to their perceived potential for reduced tobacco-related toxicant exposure and negative health effects.  However, little is known about the long-term comparative effects of e-cigarettes and HTPs versus traditional cigarettes on aberrant extracellular matrix (ECM) protein degradation.  In the lung, changes in proteolysis can alter inflammation, cell signaling, and mucus clearance, among other processes, as part of normal lung homeostasis.  Combustible cigarette use is associated with prolonged increases in protease levels linked to increased disease pathogenesis and degradation of the lung’s connective tissue, leading to emphysema.  Although there is an established association between combustible cigarette use and abnormal protease production, gaps remain in our knowledge of how alternative product use affects protease production.

 

                DISPARITIES IN TIMING AND DEMOGRAPHICS OF WITHDRAWAL OF LIFE-SUSTAINING THERAPY FOLLOWING IN-HOSPITAL AND OUT-OF-HOSPITAL CARDIAC ARRESTS (Pulmonary / Critical Care)

Shelbi Erp, MD, University of Illinois Chicago

 

Post-cardiac arrest patients often undergo withdrawal of life-sustaining therapy (WLST) due to poor perceived neurologic prognosis. Despite guidelines recommending neuroprognostication and WLST decisions at least 72 hours post-arrest, early WLST remains common, potentially leading to excessive deaths. Disparities in WLST rates and timing across demographic groups may contribute to inequities in post-cardiac arrest outcomes. These disparities and their driving factors are poorly understood, particularly between in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) populations.