Champion, H. C., Champion, H. C., Vanderpool, R., Vanderpool, R., Garcia, J. G., Garcia, J. G., Yuan, J., Yuan, J., Abidov, A., Abidov, A., Desai, A., Desai, A., Knapp, S. M., Knapp, S. M., Knoper, S. R., Knoper, S. R., Hansen, L., Hansen, L., Simon, M., , Simon, M., et al. (2017). Treprostinil decreases right ventricular contractility but improves ejection fraction and exercise capacity in pulmonary arterial hypertension. European Respiratory J.
Singleton, P. A., Mambetsariev, N., Lennon, F. E., Mathew, B., Siegler, J. H., Moreno-Vinasco, L., Salgia, R., Moss, J., & Garcia, J. G. (2010). Methylnaltrexone potentiates the anti-angiogenic effects of mTOR inhibitors. Journal of angiogenesis research, 2(1), 5.
Recent cancer therapies include drugs that target both tumor growth and angiogenesis including mammalian target of rapamycin (mTOR) inhibitors. Since mTOR inhibitor therapy is associated with significant side effects, we examined potential agents that can reduce the therapeutic dose.
Sun, X., Mathew, B., Sammani, S., Jacobson, J. R., & Garcia, J. G. (2016). Simvastatin- Induced Sphingosine 1−Phosphate Receptor 1 Expression is KLF2-Dependent in Human Lung Endothelial Cells. Pulmonary Circulation.
Siegler, J. H., Siegler, J. H., Garcia, J. G., Garcia, J. G., Wang, T., Wang, T., Casanova, N., Casanova, N., Gonzalez-Garay, M. L., Gonzalez-Garay, M. L., Karnes, J. H., Karnes, J. H., Ayshiev, D., Ayshiev, D., Sun, X., Sun, X., Lynn, H. D., & Lynn, H. D. (2018). Single nucleotide polymorphisms (SNPs) in the MYLKP1 pseudogene are associated with increased colon cancer risk in African Americans. PLOS ONE.
Desai, A., Black, S., Wang, T., Garcia, J. G., Sun, X., Adyshev, D., Kelly, G. T., Camp, S. M., & Elangovan, V. R. (2016). Endotoxin- and mechanical stress-induced epigenetic changes in the regulation of the nicotinamide phosphoribosyltransferase promoter. Pulmonary circulation, 6(4), 539-544.
Mechanical ventilation, a lifesaving intervention for patients with acute respiratory distress syndrome (ARDS), also unfortunately contributes to excessive mechanical stress and impaired lung physiological and structural integrity. We have elsewhere established the pivotal role of increased nicotinamide phosphoribosyltransferase (NAMPT) transcription and secretion as well as its direct binding to the toll-like receptor 4 (TLR4) in the progression of this devastating syndrome; however, regulation of this critical gene in ventilator-induced lung injury (VILI) is not well characterized. On the basis of an emerging role for epigenetics in enrichment of VILI and CpG sites within the NAMPT promoter and 5'UTR, we hypothesized that NAMPT expression and downstream transcriptional events are influenced by epigenetic mechanisms. Concomitantly, excessive mechanical stress of human pulmonary artery endothelial cells or lipopolysaccharide (LPS) treatment led to both reduced DNA methylation levels in the NAMPT promoter and increased gene transcription. Histone deacetylase inhibition by trichostatin A or Sirt-1-silencing RNA attenuates LPS-induced NAMPT expression. Furthermore, recombinant NAMPT administration induced TLR4-dependent global H3K9 hypoacetylation. These studies suggest a complex epigenetic regulatory network of NAMPT in VILI and ARDS and open novel strategies for combating VILI and ARDS.
