Browsing by Subject "pulmonary artery"

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    Sphingosine Kinase 1 Regulates the Pulmonary Vascular Immune Response
    (Springer, 2021-09) Bai, Yang; Lockett, Angelia D.; Gomes, Marta T.; Stearman, Robert S.; Machado, Roberto F.; Medicine, School of Medicine
    The aberrant proliferation of pulmonary artery smooth muscle (PASMCs) cells is a defining characteristic of pulmonary arterial hypertension (PAH) and leads to increased vascular resistance, elevated pulmonary pressure, and right heart failure. The sphingosine kinase 1 (SPHK1)/sphingosine-1 phosphate/sphingosine-1 phosphate receptor 2 pathway promotes vascular remodeling and induces PAH. The aim of this study was to identify genes and cellular processes that are modulated by over-expression of SPHK1 in human PASMCs (hPASMCs). RNA was purified and submitted for RNA sequencing to identify differentially expressed genes. Using a corrected p-value threshold of <0.05, there were 294 genes significantly up-regulated while 179 were significantly down-regulated. Predicted effects of these differentially expressed genes were evaluated using the freeware tool Enrichr to assess general gene set over-representation (enrichment) and ingenuity pathway analysis (IPA™) for upstream regulator predictions. We found a strong change in genes that regulated the cellular immune response. IL6, STAT1, and PARP9 were elevated in response to SPHK1 over-expression in hPASMCs. The gene set enrichment mapped to a few immune-modulatory signaling networks, including IFNG. Furthermore, PARP9 and STAT1 protein were elevated in primary hPASMCs isolated from PAH patients. In conclusion, these data suggest a role of Sphk1 regulates pulmonary vascular immune response in PAH.
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    Variation in Hospital-use and Outcomes Associated with Pulmonary Artery Catheterization in Heart Failure in the United States
    (American Heart Association, 2016-11) Khera, Rohan; Pandey, Ambarish; Kumar, Nilay; Singh, Rajeev; Bano, Shah; Golwala, Harsh; Kumbhani, Dharam J.; Girotra, Saket; Fonarow, Gregg C.; Medicine, School of Medicine
    Background There has been an increase in the use of pulmonary artery (PA) catheters in heart failure (HF) in the United States in recent years. However, patterns of hospital-use and trends in patient outcomes are not known. Methods and Results In the National Inpatient Sample 2001–2012, using ICD-9 codes we identified 11,888,525 adult (≥18 years) HF hospitalizations nationally, of which an estimated 75,209 (SE 0.6%) received a PA catheter. In 2001, the number of hospitals with ≥1 PA catheterization was 1753, decreasing to 1183 in 2011. The mean PA catheter use per hospital trended from 4.9/year in 2001 (limits 1–133) to 3.8/year in 2007 (limits 1–46), but increased to 5.5/year in 2011 (limits 1–70). During 2001–2006, PA catheterization declined across hospitals; however, in 2007–2012 there has been a disproportionate increase at hospitals with large bedsize, teaching programs, and advanced HF capabilities. The overall in-hospital mortality with PA catheter use was higher than without PA catheter use (13.1% vs. 3.4%, P<0.0001), however, in propensity-matched analysis, differences in mortality between these groups have attenuated over time – risk-adjusted odds ratio for mortality for PA-catheterization, 1.66 (95% CI 1.60–1.74) in 2001–2003 down to 1.04 (95% CI 0.97– 1.12) in 2010–2012. Conclusions There is substantial hospital-level variability in PA catheterization in HF along with increasing volume at fewer hospitals overrepresented by large, academic hospitals with advanced HF capabilities. This is accompanied by a decline in excess mortality associated with PA catheterization.