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Angiogenesis is an energy-demanding process; however, the role of cellular energy pathways and their regulation by extracellular stimuli, especially extracellular nucleotides, remain largely unexplored. Using metabolic inhibitors of glycolysis (2-deoxyglucose) and oxidative phosphorylation (OXPHOS) (oligomycin, rotenone, and FCCP), we demonstrate that glycolysis and OXPHOS are both essential for angiogenic responses of vasa vasorum endothelial cell (VVEC). Treatment with P2R agonists, ATP, and 2-methylthioadenosine diphosphate trisodium salt (MeSADP), but not P1 receptor agonist, adenosine, increased glycolytic activity in VVEC (measured by extracellular acidification rate and lactate production). Stimulation of glycolysis was accompanied by increased levels of phospho-phosphofructokinase B3, hexokinase (HK), and GLUT-1, but not lactate dehydrogenase. Moreover, extracellular ATP and MeSADP, and to a lesser extent adenosine, increased basal and maximal oxygen consumption rates in VVEC. These effects were potentiated when the cells were cultured in 20 mM galactose and 5 mM glucose compared with 25 mM glucose. Treatment with P2R agonists decreased phosphorylation of pyruvate dehydrogenase (PDH)-E1α and increased succinate dehydrogenase (SDH), cytochrome oxidase IV, and β-subunit of F1F0 ATP synthase expression. In addition, P2R stimulation transiently elevated mitochondrial Ca2+ concentration, implying involvement of mitochondria in VVEC angiogenic activation. We also demonstrated a critical role of phosphatidylinositol 3-kinase and Akt pathways in lactate production, PDH-E1α phosphorylation, and the expression of HK, SDH, and GLUT-1 in ATP-stimulated VVEC. Together, our findings suggest that purinergic and metabolic regulation of VVEC energy pathways is essential for VV angiogenesis and may contribute to pathologic vascular remodeling in pulmonary hypertension.

Objective To determine the acceptability by patients of corporal plication for Peyronie's disease. Patients and methods A postal questionnaire was sent to 69 patients who had undergone corporal plication for Peyronie's disease between 1992 and 1999, to ascertain the subjective outcome and acceptance by the patients and their sexual partners of the results of the procedure. Of the 65 patients who were still alive, 44 (68%) returned the questionnaire. Results The mean (range) follow-up was 4.1 (0.5±7.25) years and the mean age of the patients 54.6 (32±80) years. Of the 44 patients responding, 24 (55%) were sexually active; after surgery, 16 (36%) had signi®cant impairment of erections, seven (16%) continued to have signi®cant penile discomfort and 15 (34%) could feel nodules at the suture site. Twenty®ve (57%) patients reported a mild and six (14%) a severe persistent penile deformity; 40 (90%) reported having a shorter penis, of whom 22 (55%) thought it signi®cant. Overall, 14 (32%) reported`numbness' of the glans penis. Only 23 (52%) of the patients would recommend the surgery, with 25 (57%) reporting a deterioration in their overall quality of life. Of the partners of the evaluable patients, 38 (86%) responded, and a signi®cant deterioration in sexual performance was reported by 19 (35%). Conclusions Overall, the long-term results of corporal plication appear to be disappointing. These poor results could be related to a current lack of understanding of the natural history and progression of the disease, to case selection, or to the surgery. We intend to use these results to counsel our patients before such surgery and inform them of the possible outcome in the long term.