Leptin deficiency recapitulates the histological features of pulmonary arterial hypertension in mice

International Journal of Clinical and Experimental Pathology

Volumn 7, Issue 5, 2014, Pages 1935-1946

  Aytekin, Metin ^a,b   Tonelli, Adriano R ^b   Farver, Carol F ^b   Feldstein, Ariel E ^c   Dweik, Raed A ^b  

^a ERCIYES UNIVERSITY   (Turkey)

^b LERNER RESEARCH INSTITUTE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Leptin; Obesity; Pulmonary hypertension; Vasculature

Indexed keywords

ACTA2 PROTEIN, MOUSE; ACTIN; HYALURONIC ACID; LEPTIN;

ANIMAL; C57BL MOUSE; CELL PROLIFERATION; DEFICIENCY; DISEASE MODEL; GENETICS; HEART RIGHT VENTRICLE HYPERTROPHY; KNOCKOUT MOUSE; MACROPHAGE; MALE; METABOLISM; MYOFIBROBLAST; PATHOLOGY; PULMONARY ARTERY; PULMONARY HYPERTENSION; VASCULAR REMODELING;

ACTINS; ANIMALS; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; HYALURONIC ACID; HYPERTENSION, PULMONARY; HYPERTROPHY, RIGHT VENTRICULAR; LEPTIN; MACROPHAGES; MALE; MICE, INBRED C57BL; MICE, KNOCKOUT; MYOFIBROBLASTS; PULMONARY ARTERY; VASCULAR REMODELING;

EID: 84902505482     PISSN: None     EISSN: 19362625     Source Type: Journal    
DOI: None     Document Type: Article

References (57)

1. Breslow MJ, Min-Lee K, Brown DR, Chacko VP, Palmer D and Berkowitz DE. Effect of leptin deficiency on metabolic rate in ob/ob mice. Am J Physiol 1999; 276: E443-449.
2. Campfield LA, Smith FJ and Burn P. The OB protein (leptin) pathway--a link between adipose tissue mass and central neural networks. Horm Metab Res 1996; 28: 619-632.
3. Mark AL, Correia M, Morgan DA, Shaffer RA and Haynes WG. State-of-the-art-lecture: Obesity- induced hypertension: new concepts from the emerging biology of obesity. Hypertension 1999; 33: 537-541.
4. Haynes WG, Sivitz WI, Morgan DA, Walsh SA and Mark AL. Sympathetic and cardiorenal actions of leptin. Hypertension 1997; 30: 619-623.
5. Morgan DA, Thedens DR, Weiss R and Rahmouni K. Mechanisms mediating renal sympathetic activation to leptin in obesity. Am J Physiol Regul Integr Comp Physiol 2008; 295: R1730-1736.
6. Yang R and Barouch LA. Leptin signaling and obesity: cardiovascular consequences. Circ Res 2007; 101: 545-559.
7. Anagnostoulis S, Karayiannakis AJ, Lambropoulou M, Efthimiadou A, Polychronidis A and Simopoulos C. Human leptin induces angiogenesis in vivo. Cytokine 2008; 42: 353-357.
8. Bouloumie A, Drexler HC, Lafontan M and Busse R. Leptin, the product of Ob gene, promotes angiogenesis. Circ Res 1998; 83: 1059-1066.
9. Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ and Flores-Riveros JR. Biological action of leptin as an angiogenic factor. Science 1998; 281: 1683-1686.
10. Winters B, Mo Z, Brooks-Asplund E, Kim S, Shoukas A, Li D, Nyhan D and Berkowitz DE. Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lep(ob)) mice. J Appl Physiol 2000; 89: 2382-2390.
11. Lembo G, Vecchione C, Fratta L, Marino G, Trimarco V, d'Amati G and Trimarco B. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 2000; 49: 293-297.
12. Naseem KM. The role of nitric oxide in cardiovascular diseases. Mol Aspects Med 2005; 26: 33-65.
13. Ku IA, Farzaneh-Far R, Vittinghoff E, Zhang MH, Na B and Whooley MA. Association of low leptin with cardiovascular events and mortality in patients with stable coronary artery disease: The Heart and Soul Study. Atherosclerosis 2011; 217: 503-8.
14. Piemonti L, Calori G, Mercalli A, Lattuada G, Monti P, Garancini MP, Costantino F, Ruotolo G, Luzi L and Perseghin G. Fasting plasma leptin, tumor necrosis factor-alpha receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women: impact on cardiovascular mortality. Diabetes Care 2003; 26: 2883-2889.
15. Scholze A, Rattensperger D, Zidek W and Tepel M. Low serum leptin predicts mortality in patients with chronic kidney disease stage 5. Obesity (Silver Spring) 2007; 15: 1617-1622.
16. Tonelli AR, Aytekin M, Feldstein AE and Dweik RA. Leptin levels predict survival in pulmonary arterial hypertension. Pulm Circ 2012; 2: 214-219.
17. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J, Harrington RA, Anderson JL, Bates ER, Bridges CR, Eisenberg MJ, Ferrari VA, Grines CL, Hlatky MA, Jacobs AK, Kaul S, Lichtenberg RC, Moliterno DJ, Mukherjee D, Pohost GM, Schofield RS, Shubrooks SJ, Stein JH, Tracy CM, Weitz HH and Wesley DJ. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation 2009; 119: 2250-2294.
18. Stacher E, Graham BB, Hunt JM, Gandjeva A, Groshong SD, McLaughlin VV, Jessup M, Grizzle WE, Aldred MA, Cool CD and Tuder RM. Modern age pathology of pulmonary arterial hypertension. Am J Respir Crit Care Med 2012; 186: 261-272.
19. Li L, Mamputu JC, Wiernsperger N and Renier G. Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: inhibitory effect of metformin. Diabetes 2005; 54: 2227-2234.
20. Quehenberger P, Exner M, Sunder-Plassmann R, Ruzicka K, Bieglmayer C, Endler G, Muellner C, Speiser W and Wagner O. Leptin induces endothelin-1 in endothelial cells in vitro. Circ Res 2002; 90: 711-718.
21. Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF and Rabinovitch M. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43: 13S-24S.
22. Giaid A, Yanagisawa M, Langleben D, Michel RP, Levy R, Shennib H, Kimura S, Masaki T, Duguid WP and Stewart DJ. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993; 328: 1732-1739.
23. Shao D, Park JE and Wort SJ. The role of endothelin-1 in the pathogenesis of pulmonary arterial hypertension. Pharmacol Res 2011; 63: 504-511.
24. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L and Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-432.
25. Ingalls AM, Dickie MM and Snell GD. Obese, a new mutation in the house mouse. J Hered 1950; 41: 317-318.
26. Hmisc: Harrell Miscellaneous, 2010. Available from: http://cran.r-project.org/web/packages/ Hmisc/index.html [Last accessed on 2011 Sep].
27. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, et al. Serum immunoreactive-leptin concentrations in normal- weight and obese humans. N Engl J Med 1996; 334: 292-295.
28. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995; 1: 1155-1161.
29. Ip MS, Lam KS, Ho C, Tsang KW and Lam W. Serum leptin and vascular risk factors in obstructive sleep apnea. Chest 2000; 118: 580-586.
30. Sikka G, Yang R, Reid S, Benjo A, Koitabashi N, Camara A, Baraban E, O'Donnell CP, Berkowitz DE and Barouch LA. Leptin is essential in maintaining normal vascular compliance independent of body weight. Int J Obes (Lond) 2010; 34: 203-206.
31. Singhal A, Farooqi IS, Cole TJ, O'Rahilly S, Fewtrell M, Kattenhorn M, Lucas A and Deanfield J. Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease? Circulation 2002; 106: 1919-1924.
32. Martin SS, Qasim A and Reilly MP. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol 2008; 52: 1201-1210.
33. Unger RH. Hyperleptinemia: protecting the heart from lipid overload. Hypertension 2005; 45: 1031-1034.
34. Vecchione C, Maffei A, Colella S, Aretini A, Poulet R, Frati G, Gentile MT, Fratta L, Trimarco V, Trimarco B and Lembo G. Leptin effect on endothelial nitric oxide is mediated through Akt-endothelial nitric oxide synthase phosphorylation pathway. Diabetes 2002; 51: 168-173.
35. Fruhbeck G. Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes 1999; 48: 903-908.
36. Aytekin M, Comhair SA, de la Motte C, Bandyopadhyay SK, Farver CF, Hascall VC, Erzurum SC and Dweik RA. High levels of hyaluronan in idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 2008; 295: L789-799.
37. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL and Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796-1808.
38. Voelkel NF and Tuder RM. Cellular and molecular mechanisms in the pathogenesis of severe pulmonary hypertension. Eur Respir J 1995; 8: 2129-2138.
39. Tuder RM, Groves B, Badesch DB and Voelkel NF. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 1994; 144: 275-285.
40. Gerasimovskaya E, Kratzer A, Sidiakova A, Salys J, Zamora M and Taraseviciene-Stewart L. Interplay of macrophages and T cells in the lung vasculature. American journal of physiology. Am J Physiol Lung Cell Mol Physiol 2012; 302: L1014-1022.
41. El Chami H and Hassoun PM. Immune and inflammatory mechanisms in pulmonary arterial hypertension. Prog Cardiovasc Dis 2012; 55: 218-228.
42. Kherbeck N, Tamby MC, Bussone G, Dib H, Perros F, Humbert M and Mouthon L. The role of inflammation and autoimmunity in the pathophysiology of pulmonary arterial hypertension. Clin Rev Allergy Immunol 2013; 44: 31-38.
43. Savai R, Pullamsetti SS, Kolbe J, Bieniek E, Voswinckel R, Fink L, Scheed A, Ritter C, Dahal BK, Vater A, Klussmann S, Ghofrani HA, Weissmann N, Klepetko W, Banat GA, Seeger W, Grimminger F and Schermuly RT. Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 2012; 186: 897-908.
44. Shao D, Park JE and Wort SJ. The role of endothelin-1 in the pathogenesis of pulmonary arterial hypertension. Pharmacol Res 2011; 63: 504-511.
45. Stewart DJ, Levy RD, Cernacek P and Langleben D. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Intern Med 1991; 114: 464-469.
46. Cacoub P, Dorent R, Nataf P and Carayon A. Endothelin-1 in pulmonary hypertension. N Engl J Med 1993; 329: 1967-1968.
47. Cacoub P, Dorent R, Nataf P, Carayon A, Riquet M, Noe E, Piette JC, Godeau P and Gandjbakhch I. Endothelin-1 in the lungs of patients with pulmonary hypertension. Cardiovasc Res 1997; 33: 196-200.
48. van Wolferen SA, Boonstra A, Marcus JT, Marques KM, Bronzwaer JG, Postmus PE and Vonk-Noordegraaf A. Right ventricular reverse remodelling after sildenafil in pulmonary arterial hypertension. Heart 2006; 92: 1860-1861.
49. Kawut SM, Horn EM, Berekashvili KK, Garofano RP, Goldsmith RL, Widlitz AC, Rosenzweig EB, Kerstein D and Barst RJ. New predictors of outcome in idiopathic pulmonary arterial hypertension. Am J Cardiol 2005; 95: 199-203.
50. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F, Dromer C, Pison C, Reynaud-Gaubert M, Haloun A, Laurent M, Hachulla E, Cottin V, Degano B, Jais X, Montani D, Souza R and Simonneau G. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122: 156-163.
51. Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, Lubina JA, Patane J, Self B, Hunt P and McCamish M. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999; 282: 1568-1575.
52. Martin SS, Qasim A and Reilly MP. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol 2008; 52: 1201-1210.
53. Sikka G, Yang R, Reid S, Benjo A, Koitabashi N, Camara A, Baraban E, O'Donnell CP, Berkowitz DE and Barouch LA. Leptin is essential in maintaining normal vascular compliance independent of body weight. Int J Obes (Lond) 2010; 34: 203-206.
54. Mantzoros CS, Liolios AD, Tritos NA, Kaklamani VG, Doulgerakis DE, Griveas I, Moses AC and Flier JS. Circulating insulin concentrations, smoking, and alcohol intake are important independent predictors of leptin in young healthy men. Obes Res 1998; 6: 179-186.
55. Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A and Sattar N. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation 2001; 104: 3052-3056.
56. Wolk R, Berger P, Lennon RJ, Brilakis ES, Johnson BD and Somers VK. Plasma leptin and prognosis in patients with established coronary atherosclerosis. J Am Coll Cardiol 2004; 44: 1819-1824.
57. Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB and Flier JS. Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med 1995; 1: 1311-1314.