Previous studies, based on hypoxiainduced PH in a relatively earlier/or developing stage of PH animal model describes that the upregulation of hypoxia-induced factor, in combination with HIF-1b, activates over 100 genes involved in metabolism. In particular, there is increased glucose uptake via GLUT1 and GLUT3 as well as inhibition of the pyruvate dehydrogenase complex by pyruvate dehydrogenase kinase that normally oxidizes pyruvate to acetyl-CoA for the Krebs cycle. Other studies have shown that resemble characteristics of growing tumor cells in cancer. These cells are characterized by the “Warburg effect”, as hyperproliferative tumor cells under hypoxic conditions use aerobic glycolysis with resultant changes in its mitochondrial redox state to escape apoptosis in the developing stage of the PH. Results from previous studies that suggest for increased glycolysis had worked with experimental models of PH at the relatively early stage, such as in vitro studies using smooth muscle cells from animals exposed to 2–3 weeks of hypoxia or in vitro human pulmonary microvascular endothelial cells s transfected with a BMPRII mutation. In several of these studies, PH was induced by experimental measures and studies ICI 182780 focused solely on one cell type, which would ignore possible cellcell interactions that occur in the vascular remodeling process. In contrast to previous studies, our results were obtained from the severe human PAH lung rather than from animal models, which may be the underlying reason for the observation of reduced glycolysis. It remains elusive whether changes in metabolic pathways, for example, the rate of glycolysis, can reflect different stages in the progression of human pulmonary arterial hypertension. If so, such changes in glycolytic intermediates could serve as potential biomarkers for the diagnosis and prognosis of the disease. Nitrogen-rich enzymes and nitrogencontaining precursors are involved in the production of what are termed C-based defenses, however, so this classification of defenses as C- or N-based may be an oversimplification and confound interpretation of responses to resources in the framework of the CNBH or GDBH. There has, in fact, been much debate as to the utility of the CNBH, and it has also been erroneously applied. Nonetheless, the empirical support for this hypothesis shows predicted patterns of phenotypic changes in defenses for temperate woody, herbaceous, and tropical species. The GDBH is more detailed than the CNBH and predicts a negative correlation between growth and defense under conditions of moderate to high resource availability. The GDBH is difficult to test because: 1) a broad range of resource availability must be included in studies, 2) most variables assessed are merely correlates of the plastic physiological processes that are part of the hypothesis, and 3) it is difficult to XL880 ensure the maintenance of experimental resource conditions throughout a plant’s growth. Despite these challenges, valuable insights on trade-offs and priorities in plant resource allocation can be gained from studies addressing aspects of the GDBH.