Translational Medical Research Commons^™

Ticagrelor Reduces Thromboinflammatory Markers In Patients With Pneumonia, Travis R. Sexton, Guoying Zhang, Tracy E. Macaulay, Leigh Ann Callahan, Richard Charnigo, Olga A. Vsevolozhskaya, Zhenyu Li, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y₁₂ receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches …

Acute Pressor Response To Psychosocial Stress Is Dependent On Endothelium‐Derived Endothelin‐1, Brandon M. Fox, Bryan K. Becker, Analia S. Loria, Kelly A. Hyndman, Chunhua Jin, Hannah Clark, Robin Johns, Masashi Yanagisawa, David M. Pollock, Jennifer S. Pollock

Pharmacology and Nutritional Sciences Faculty Publications

Background

Acute psychosocial stress provokes increases in circulating endothelin‐1 (ET‐1) levels in humans and animal models. However, key questions about the physiological function and cellular source of stress‐induced ET‐1 remain unanswered. We hypothesized that endothelium‐derived ET‐1 contributes to the acute pressor response to stress via activation of the endothelin A receptor.

Methods and Results

Adult male vascular endothelium‐specific ET‐1 knockout mice and control mice that were homozygous for the floxed allele were exposed to acute psychosocial stress in the form of cage switch stress (CSS), with blood pressure measured by telemetry. An acute pressor response was elicited by CSS in …

Rad Gtpase Deletion Atenuates Post-Ischemic Cardiac Dysfunction And Remodeling, Janet R. Manning, Lakshman Chelvarajan, Bryana R. Levitan, Catherine Nicole Kaminski Withers, Prabhakara R. Nagareddy, Christopher M. Haggerty, Brandon K. Fornwalt, Erhe Gao, Himi Tripathi, Ahmed Abdel-Latif, Douglas A. Andres, Jonathan Satin

Physiology Faculty Publications

The protein Rad interacts with the L-type calcium channel complex to modulate trigger Ca²⁺ and hence to govern contractility. Reducing Rad levels increases cardiac output. Ablation of Rad also attenuated the inflammatory response following acute myocardial infarction. Future studies to target deletion of Rad in the heart could be conducted to establish a novel treatment paradigm whereby pathologically stressed hearts would be given safe, stable positive inotropic support without arrhythmias and without pathological structural remodeling. Future investigations will also focus on establishing inhibitors of Rad and testing the efficacy of Rad deletion in cardioprotection relative to the time of …