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Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population.
NPJ Syst Biol Appl
January 2025
United Therapeutics Corporation, Silver Spring, MD, USA.
Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute walk distance in the context of oral treprostinil clinical studies. We generated a virtual population that spanned the range of clinical observations and then calibrated virtual patient-specific weights to match clinical trials.
View Article and Find Full Text PDFOff-pump Laks-type central shunt for tricuspid atresia with small branch pulmonary arteries.
Multimed Man Cardiothorac Surg
January 2025
• Department of Cardiac Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia • King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia • College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia.
Prostaglandin E1 is a potent vasodilator that prevents the ductus arteriosus from closing. Its use in neonates with cyanotic heart defects has revolutionized the management of children with cyanotic heart defects. Although the use of prostaglandin E1 is a temporary solution, the establishment of dependable pulmonary blood flow is of paramount importance.
View Article and Find Full Text PDFAnandamide Inhibits Vascular Smooth Muscle Migration, Endothelial Adhesion Protein Expression and Monocyte Adhesion of Human Coronary Artery Cells.
Cells
December 2024
Institute of Pharmacology and Toxicology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany.
Endocannabinoids have been shown to play a complex role in the pathophysiology of a number of cardiovascular disorders. In the present study, the effects of the two major endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were investigated in human coronary artery smooth muscle cells (HCASMC) and human coronary artery endothelial cells (HCAEC) with regard to potential atheroprotective and anti-inflammatory effects. In HCASMC, AEA showed an inhibitory effect on platelet-derived growth factor-induced migration, but not proliferation, independent of major cannabinoid-activatable receptors (CB, CB, TRPV1), while 2-AG left both responses unaffected.
View Article and Find Full Text PDFEndothelial cell-selective adhesion molecule deficiency exhibits increased pulmonary vascular resistance due to impaired endothelial nitric oxide signaling.
Am J Physiol Heart Circ Physiol
February 2025
Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, United States.
Endothelial cell-selective adhesion molecule (ESAM) is a member of tight junction molecules, highly abundant in the heart and the lung, and plays a role in regulating endothelial cell permeability. We previously reported that mice with genetic ESAM deficiency () exhibit coronary microvascular dysfunction leading to the development of left ventricular diastolic dysfunction. Here, we hypothesize that mice display impairments in the pulmonary vasculature, affecting the overall pulmonary vascular resistance (PVR).
View Article and Find Full Text PDFTransient receptor potential vanilloid 4 gene-deficiency attenuates the inhibitory effect of 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid on vascular permeability in mice.
J Pharmacol Sci
January 2025
Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan; Department of Veterinary Pharmacology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan; Food and Animal Systemics, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. Electronic address:
We investigated whether an anti-inflammatory lipid metabolite named 5,6-DiHETE reduces vascular permeability by inhibiting TRPV4 channels in vivo. In wild-type (WT) mice, histamine-induced dye extravasation was reduced by pre-administration of 5,6-DiHETE. In TRPV4-deficient mice, extravasation and histamine-induced edema were already reduced, and 5,6-DiHETE had no additional effect.
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