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Research findings

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Research findings

  1. 1. Research Findings Dr. PM PiattiDr. PM Piatti Scientific InstituteScientific Institute San RaffaeleSan Raffaele MilanoMilano
  2. 2. PIATTI PM, MONTI LD, CONTI M, BARUFFALDI L, GALLI L, PHAN VC, GUAZZINI B, PONTIROLI AE, POZZA G Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in man. Diabetes, 45:316-321, 1996.
  3. 3. The purpose of the study was to evaluate fasting endothelin-1 levels in subjects with syndrome X, in subjects with insulinoma, and in normal subjects. The single and synergistic contributions of insulin and triglyceride levels to endothelin-1 release were studied in normal subjects. Piatti et al Diabetes 1996; 45: 316-321
  4. 4. Subjects with metabolic syndrome X showed higher endothelin-1 levels than normal subjects and subjects with insulinoma. These levels were reproduced in normal subjects by a simultaneous increase in insulin and triglyceride levels. Piatti et al Diabetes 1996; 45: 316-321
  5. 5. PIATTI PM, MONTI LD, VALSECCHI G, CONTI M, NASSER R, GUAZZINI B, FOCHESATO E, PHAN VC, PONTIROLI AE, POZZA G Effects of low dose heparin infusion on arterial endothelin-1 release in man. Circulation, 94:2703-2707, 1996.
  6. 6. The aim of this study was to evaluate the effect of low-dose heparin infusion on arterialized endothelin-1 (ET-1) release in the presence of fasting or high insulin levels in healthy humans. Piatti et al Circulation 1996; 94:2703-07
  7. 7. Piatti et al Circulation 1996; 94:2703-07 The present study showed that it is possible to decrease ET-1 levels by use of low-dose heparin infusion in humans. This effect seems mediated by a simultaneous increase in nitric oxide levels and is completely reversed by a mild increase in insulin concentrations.
  8. 8. PIATTI PM, MONTI LD, GALLI L, FRAGASSO G, VALSECCHI G, PONTIROLI AE Relationship between endothelin-1 concentrations and the metabolic alterations typical of the Insulin Resistance Syndrome. Metabolism 49:748-752, 2000
  9. 9. The purpose of the study was to examine the relationship between the endothelin-1 (ET-1) concentration and the metabolic variables characteristic of the insulin resistance syndrome ([IRS] hyperinsulinemia, insulin resistance, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, visceral obesity, and glycemic abnormalities). The measurement of circulating ET-1 is a well-recognized marker of endothelial atherosclerotic and cardiovascular disease. Piatti et al. Metabolism 2000, 49:748-52
  10. 10. Piatti et al. Metabolism 2000, 49:748-52 At simple regression analysis, ET-1 levels significantly correlated with insulin, glycosylated hemoglobin, body weight, waist to hip ratio, and triglyceride values. At multiple regression analysis, only triglycerides (p<0.009) and glycosylated hemoglobin (p<0.001) remained independently correlated with ET-1. This cross-sectional study indicates that glycosylated hemoglobin and triglycerides are independently correlated with ET-1 levels in patients with IRS.
  11. 11. PIATTI PM, MONTI LD, ZAVARONI I, VALSECCHI G, SOLERTE SB, POZZA G, PONTIROLI AE, REAVEN G Alterations in Nitric Oxide/Cyclic-GMP Pathway in Non Diabetic Siblings of Patients with type 2 Diabetes J Clin Endocrinol Metab 85:2416-2420, 2000
  12. 12. In this study, we have compared resistance to insulin-mediated glucose disposal and plasma concentrations of nitric oxide (NO) and cyclic-GMP in healthy volunteers with or without at least one sibling and one parent with type 2 diabetes. Piatti et al. JCEM 2000, 85:2416-2420
  13. 13. Piatti et al. JCEM 2000, 85:2416-2420 We demonstrated that alterations of the NO/cyclic-GMP pathway seem to be an early event in nondiabetic individuals with a family history of type 2 diabetes and these changes are correlated with the degree of insulin resistance.
  14. 14. PIATTI PM, MONTI LD, VALSECCHI G, MAGNI F, SETOLA E, MARCHESI F, GALLI-KIENLE M, POZZA G, ALBERTI KGMM Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients. Diabetes Care 24: 875-880, 2001
  15. 15. Piatti et al. Diabetes Care 2001, 24:875-880 The aim of this study was to evaluate whether long-term administration of arginine acting through a normalization of NO/cyclic-guanosine-3' 5'-cyclic monophosphate (cGMP) pathway was able to ameliorate peripheral and hepatic insulin sensitivity in 12 lean type 2 diabetic patients.
  16. 16. Piatti et al. Diabetes Care 2001, 24:875-880 We found that, in lean type 2 diabetic patients, treated with diet alone, L- Arginine treatment significantly improved peripheral and hepatic insulin sensitivity.
  17. 17. FRAGASSO G, PIATTI PM, MONTI LD, CHUNZENG L, VALSECCHI G, SETOLA E, PALLOSHI A, POZZA G, MARGONATO A, CHIERCHIA S Acute effects of heparin administration on the ischemic threshold of patients with coronary artery disease: Evaluation of the protective role of the metabolic modulator trimetazidine. J.Am.Coll.Cardiol. 39:413-419, 2002
  18. 18. Fragasso, Piatti et al. J Am Coll Cardiol 2002, 39:413-419 We sought to assess the effects of heparin and the potential protective effects of trimetazidine (TMZ) on exercise performance, plasma nitric oxide (NO), endothelin-1 (ET-1) and free fatty acid (FFA) release in patients with stable coronary artery disease (CAD).
  19. 19. Fragasso, Piatti et al. J Am Coll Cardiol 2002, 39:413-419 In patients with CAD, heparin reduces the ischemic threshold. Trimetazidine reduces the effects of heparin, probably by inhibiting FFA oxidation and enhancing glucose metabolism. The concomitant novel observation of reduced ET-1 release is likely to be also dependent on TMZ-induced improvement of endothelial metabolism or reduction of myocardial ischemia.
  20. 20. MONTI LD, ALLIBARDI S, PIATTI PM, VALSECCHI G, COSTA S, POZZA G, CHIERCHIA S, SAMAJA M Triglycerides impair post-ischemic recovery in isolated hearts: roles of endothelin-1 and trimetazidine. Am J Physiol Heart Circ Physiol 281:H1122- 30, 2001
  21. 21. Monti, Piatti et al. Am J Physiol Heart Circ Physiol 2001:281:H1122-30 There is growing evidence that hypertriglyceridemia exacerbates ischemic injury. We tested the hypothesis that triglycerides impair myocardial recovery from low-flow ischemia in an ex vivo model and that such an effect is related to endothelin-1.
  22. 22. Monti, Piatti et al. Am J Physiol Heart Circ Physiol 2001:281:H1122-30 We conclude that high triglyceride levels impair myocardial recovery after low-flow ischemia in association with endothelin-1 release. The endothelium-mediated effect of triglycerides on both contractile recovery and endothelin-1 release is prevented by 1 microM trimetazidine.
  23. 23. PIATTI PM, FRAGASSO G, MONTI LD, CAUMO A, PHAN CV, VALSECCHI G, COSTA S, FOCHESATO E, POZZA G, PONTIROLI AE, CHIERCHIA S Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries. Comparison with subjects with insulin resistance syndrome and normal controls. J.Am.Coll.Cardiol. 34:1452-1460, 1999
  24. 24. This study was performed to characterize the endothelial and metabolic alterations of patients with angina and angiographically normal coronary arteries ("cardiac" syndrome X [CSX]) compared with subjects with insulin resistance syndrome ("metabolic" syndrome X [MSX]) and normal controls. Piatti et al. J Am Coll Cardiol 1999, 34:1452-60
  25. 25. Piatti et al. J Am Coll Cardiol 1999, 34:1452-60 We observed that blunted nitric oxide and endothelin responsiveness to intravenously infused insulin is a typical feature of patients with angina pectoris and angiographically normal coronary arteries and may contribute to the microvascular dysfunction observed in these subjects.
  26. 26. PIATTI PM, FRAGASSO G, MONTI LD, SETOLA E, LUCOTTI P, FERMO I, PARONI R, GALLUCCIO E, POZZA G, CHIERCHIA S, MARGONATO A Acute Intravenous L-Arginine Infusion Decreases Endothelin-1 Levels and Improves Endothelial Function in Patients with Angina Pectoris and Normal Coronary Arteriograms: Correlation with ADMA Levels. Circulation 2003:107:429-36.
  27. 27. We tested the hypothesis that asymmetric dimethylarginine (ADMA) levels could be elevated and influence endothelin-1 and nitric oxide release and action in patients with cardiac syndrome X (CSX). In addition, we evaluated whether an intravenous infusion of L-arginine would improve endothelial function in these subjects. Piatti et al. Circulation 2003, 107:429-36
  28. 28. We demonstrated that ADMA levels are increased in patients with CSX and positively correlated with basal endothelin-1 levels and negatively with insulin-induced incremental levels of NOx. An increment in nitric oxide availability by an acute L-arginine infusion, decreases endothelin- 1 levels and therefore, improves endothelial function in patients with CSX. These data suggest that increased ADMA levels play a role in the abnormal vascular reactivity that is observed in patients with CSX.

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