Obesity-related pulmonary arterial hypertension in rats correlates with increased circulating inflammatory cytokines and lipids and with oxidant damage in the arterial wall but not with hypoxia

Pulmonary Circulation

Volumn 4, Issue 4, 2014, Pages 638-653

  Irwin, David C ^a   Garat, Chrystelle V ^a,b   Crossno, Joseph T ^a,b   Maclean, Paul S ^a,b   Sullivan, Timothy M ^a   Erickson, Paul F ^a   Jackman, Matthew R ^b   Harral, Julie W ^a   Reusch, Jane E B ^a,b   Klemm, Dwight J ^a,b  

^a UNIVERSITY OF COLORADO   (United States)

^b UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

Hyperlipidemia; Hypoxia; Inflammation; Insulin resistance; Obesity; Oxidant damage; Pulmonary hypertension

Indexed keywords

EID: 85026337212     PISSN: 20458932     EISSN: 20458940     Source Type: Journal    
DOI: 10.1086/678510     Document Type: Article

References (67)

1. Centers for Disease Control and Prevention. Overweight and obesity. 2010. http://www.cdc.gov/nccdphp/dnpa/obesity/index.htm.
2. National Institute ofDiabetes and Digestive and Kidney Diseases, Weight-Control Information Network. Overweight and obesity statistics. http://www.win.niddk.nih.gov/statistics/index.htm.
3. Bays H, Ballantyne C. Adiposopathy: why do adiposity and obesity cause metabolic disease? Future Lipidol 2006;1(4): 389-420.
4. Brown WV, Fujioka K, Wilson PW, Woodworth KA. Obesity: why be concerned? Am J Med 2009;122(4 suppl.):S4-S11.
5. Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health 2009;9:88.
6. Murugan AT, Sharma G. Obesity and respiratory diseases. Chronic Respir Dis 2008;5(4):233-242.
7. Dela Cruz CS, Matthay RA. Role of obesity in cardiomyopathy and pulmonary hypertension. Clin Chest Med 2009;30(3): 509-523.
8. Friedman SE, Andrus BW. Obesity and pulmonary hypertension: a review of pathophysiological mechanisms. J Obes 2012:505274. doi:10.1155/2012/505274.
9. Taraseviciute A, Voelkel NF. Severe pulmonary hypertension in postmenopausal obese women. Eur J Med Res 2006;11(5): 198-202.
10. Blankfield RP, Hudgel DW, Tapolyai AA, Zyzanski SJ. Bilateral leg edema, obesity, pulmonary hypertension, and obstructive sleep apnea. Arch Intern Med 2000;160(15):2357-2362.
11. Haque AK, Gadre S, Taylor J, Haque SA, Freeman D, Duarte A. Pulmonary and cardiovascular complications of obesity: an autopsy study of 76 obese subjects. Arch Pathol Lab Med 2008;132(9):1397-1404.
12. Mokhlesi B, Tulaimat A. Recent advances in obesity hypo-ventilation syndrome. Chest 2007;132(4):1322-1336.
13. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med 2005;118(9):948-956.
14. Voelkel NF, Mizuno S, Bogaard HJ. The role of hypoxia in pulmonary vascular diseases: a perspective. Am J Physiol Lung Cell Mol Physiol 2013;304(7):L457-L465.
15. Soumaya K. Molecular mechanisms of insulin resistance in diabetes. In: Ahman SI, ed. Diabetes: an old disease, a new insight. Advances in experimental medicine and biology, vol. 771. New York: Landes Bioscience and Springer, 2012:240-251.
16. Engfeldt P, Arner P. Lipolysis in human adipocytes: effects ofcell size, age and regional differences. In: Pfeiffer EF, ed. Proinsulin. Hormone and metabolic research supplement series, vol. 19. Stuttgart: Thieme, 1988:26-29.
17. Klop B, Elte JW, Cabezas MC. Dyslipidemia in obesity: mechanisms and potential targets. Nutrients 2013;5(4):1218-1240.
18. Majka SM, Barak Y, Klemm DJ. Adipocyte origins: weighing the possibilities. Stem Cells 2011;29(7):1034-1040.
19. Singer GM, Setaro JF. Secondary hypertension: obesity and the metabolic syndrome. J Clin Hypertens 2008;10(7):567-574.
20. Zamanian RT, Hansmann G, Snook S, Lilienfeld D, Rap-paport KM, Reaven GM, Rabinovitch M, Doyle RL. Insulin resistance in pulmonary arterial hypertension. Eur Respir J 2009;33(2):318-324.
21. Fouty B. Diabetes and the pulmonary circulation. Am J Physiol Lung Cell Mol Physiol 2008;295(5):L725-L726.
22. Levin BE, Dunn-Meynell AA, Balkan B, Keesey RE. Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol 1997; 273(2):R725-R730.
23. Zucker LM, Zucker TF. Fatty, a new mutation in the rat. J Hered 1961;52(6):275-278.
24. Brennan LA, Steinhorn RH, Wedgewood S, Mata-Greenwood E, Roark EA, Russell JA, Black SM. Increased superoxide generation is associated with pulmonary hypertension in fetal lambs: a role for NADPH oxidase. Circ Res 2003;92(6):683-691.
25. Hoshikawa Y, Ono S, Suzuki S, Tanita T, Chida M, Song C, Noda M, Tabata T, Voelkel NF, Fujimura S. Generation of oxidative stress contributes to the development of pulmonary hypertension by hypoxia. J Appl Physiol 2001;90(4):1299-1306.
26. Elmedal B, de Dam MY, Mulvany MJ, Simonsen U. The superoxide dismutase mimetic, Tempol, blunts right ventricular hypertrophy in chronic hypoxic rats. Br J Pharmacol 2004;141(1):105-113.
27. Klemm DJ, Majka SM, Crossno JT Jr., Psilas JC, Reusch JEB, Garat CV. Reduction of reactive oxygen species prevents hypoxia-induced CREB depletion in pulmonary artery smooth muscle cells. J Cardiovasc Pharmacol 2011;58(2): 181-191.
28. Lachmanova V, Hniličkova O, Povysilova V, Hampl V, Herget J. N-acetylcysteine inhibits hypoxic pulmonary hypertension most effectively in the initial phase ofchronic hypoxia. Life Sci 2005;77(2):175-182.
29. Gutierrez J, Ballinger SW, Darley-Usmar VM, Landar A. Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ Res 2006;99(9):924-932.
30. Shen GX. Oxidative stress and diabetic cardiovascular disorders: roles of mitochondria and NADPH oxidase. Can J Physiol Pharmacol 2010;88(3):241-248.
31. Meyrick BO, Perkett EA. The sequence of cellular and he-modynamic changes of chronic pulmonary hypertension induced by hypoxia and other stimuli. Am Rev Respir Dis 1989;140(5):1486-1489.
32. Abe K, Toba M, Alzoubi A, Ito M, Fagan KA, Cool CD, Voelkel NF, McMurtry IF Oka M. Formation of plexiform lesions in experimental severe pulmonary arterial hypertension. Circulation 2010;121(25):2747-2754.
33. Gomez-Arroyo JG, Farkas L, Alhussaini AA, Farkas D, Kraskauskas D, Voelkel NF, Bogaard HJ. The monocrotaline model of pulmonary hypertension in perspective. Am J Physiol Lung Cell Mol Physiol 2012;302(4):L363-L369.
34. Rondelet B, Dewachter C, Kerbaul F, Kang X, Fesler P, Bri-mioulle S, Naeije R, Dewachter L. Prolonged overcirculation-induced pulmonary arterial hypertension as a cause of right ventricular failure. Eur Heart J 2012;33(8):1017-1026.
35. Huisamen B, Dietrich D, Bezuidenhout N, Lopes J, Flepisis B, Blackhurst D, Lochner A. Early cardiovascular changes occurring in diet-induced, obese insulin-resistant rats. Mol Cell Biochem 2012;368(1):37-45.
36. Maarman G, Marais E, Lochner A, du Toit EF. Effect of chronic CPT-1 inhibition on myocardial ischemia-reperfusion injury (I/R) in a model of diet-induced obesity. Cardiovasc Drugs Ther 2012;26(3):205-216.
37. Smith PM, Ferguson AV. Cardiovascular actions of leptin in the subfornical organ are abolished by diet-induced obesity. J Neuroendocrinol 2012;24(3):504-510.
38. Johnson PR, Stern JS, Horwitz BA, Harris RE Jr., Greene SF. Longevity in obese and lean male and female rats of the Zucker strain: prevention of hyperphagia. Am J Clin Nutr 1997;66(4):890-903.
39. Lam CS, Borlaug BA, Kane GC, Enders FT, Rodeheffer RJ, Redfield MM. Age-associated increases in pulmonary artery systolic pressure in the general population. Circulation 2009;119(20):2663-2670.
40. Bachschmid MM, Schildknecht S, Matsui R, Zee R, Haeussler H, Cohen RA, Pimental D, van der Loo B. Vascular aging: chronic oxidative stress and impairment of re-dox signaling—consequences for vascular homeostasis. Ann Med 2013;45(1):17-36.
41. Christon R, Drouin O, Marette A. Redox modulation ofinsu-lin signaling and endothelial function. Antioxid Redox Signal 2005;7(78):1062-1070.
42. Hennig B, Toborek M, McClain CJ. High-energy diets, fatty acids and endothelial function: implications for atherosclerosis. J Am Coll Nutr 2001;20(2):97-105.
43. Bell JA, Reed MA, Consitt LA, Martin OJ, Haynie KR, Hulver MW, Muoio DM, Dohm GL. Lipid partitioning, incomplete fatty acid oxidation, and insulin signal transduc-tion in primary human muscle cells: effects of severe obesity, fatty acid incubation, and fatty acid translocase/CD36 overexpression. J Clin Endocrinol Metab 2010;95(7):3400-3410.
44. Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, Ilkayeva O, Bain J, et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 2008;7(1):45-56.
45. Moore KH, Radloff JF, Hull FE, Sweeley CC. Incomplete fatty acid oxidation by ischemic heart: /?-hydroxy fatty acid production. Am J Physiol Heart Circ Physiol 1980;239(2): H257-H265.
46. Davi G, Falco A, Patrono C. Lipid peroxidation in diabetes mellitus. Antioxid Redox Signal 2005;7(1-2):256-268.
47. Pratico D. Prostanoid and isoprostanoid pathways in athero-genesis. Atherosclerosis 2008;201(1):8-16.
48. Bockhkov VN, Oskolkova OV, Birukov KG, Levonen AL, Binder CJ, Stockl J. Generation and biological activities of oxidized phospholipids. Antioxid Redox Signal 2010;12(8): 1009-1059.
49. Steiner MK, Syrkina OL, Kolliputi N, Mark EJ, Hales CA, Waxman AB. Interleukin-6 overexpression induces pulmonary hypertension. Circ Res 2009;104(2):236-244.
50. Savale L, Tu L, Rideau D, Izziki M, Maitre B, Adnot S, Eddahibi S. Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice. Respir Res 2009;10:6.
51. Chaouat A, Savale L, Chouaid C, Tu L, Sztrymf B, Canuet M, Maitre B, et al. Role for interleukin-6 in COPD-related pulmonary hypertension. Chest 2009;136(3):678-687.
52. Ikeda Y, Yonemitsu Y, Kataoka C, Kitamoto S, Yamaoka T, Nishida KI, Takeshita A, Egashira K, Sueishi K. Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary hypertension in rats. Am J Physiol Heart Circ Physiol 2002;283 (5):H2021-H2028.
53. Li M, Riddle SR, Frid MG, El Kasmi KC, McKinsey TA, Sokol RJ, Strassheim D, et al. Emergence of fibroblasts with a proinflammatory epigenetically altered phenotype in severe pulmonary hypertension. J Immunol 2011;187(5):2711-2722.
54. Sanchez O, Marcos E, Perros F, Tu L, Humbert M, Dartevelle P, Simonneau G, Adnot S, Eddahibi S. Role of endothelium-derived CC chemokine ligand 2 in idiopathic pulmonary hypertension. Am J Respir Crit Care Med 2007; 176(10):1041-1047.
55. Cao H. Adipocytokines in obesity and metabolic disease. J Endocrinol 2014;220(2):T47-T59.
56. del Aguila LF, Claffey KP, Kirwan JP. TNF-a impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells. Am J Physiol Endocrinol Metab 1999; 276(5):E849-E855.
57. Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes 2002;51(12):3391-3399.
58. Summer R, Walsh K, Medoff BD. Obesity and pulmonary arterial hypertension: is adiponectin the molecular link between these condition? Pulm Circ 2011;1(4):440-447.
59. Hansmann G, Rabinovitch M. The protective role of adipo-nectin in pulmonary vascular disease. Am J Physiol Lung Cell Mol Physiol 2010;298(1):L1-L2.
60. Summer R, Fiack CA, Ikeda Y, Sato K, Dwyer D, Ouchi N, Fine A, Farber HW, Walsh K. Adiponectin deficiency: a model of pulmonary hypertension associated with pulmonary vascular disease. Am J Physiol Lung Cell Mol Physiol 2009;297(3):L432-L438.
61. Nakagawa Y, Kishida K, Kihara S, Funahashi T, Shimomura I. Adiponectin ameliorates hypoxia-induced pulmonary arterial remodeling. Biochem Biophys Res Commun 2009;382 (1):183-188.
62. Weng M, Raher MJ, Leyton P, Combs TP, Scherer PE, Bloch KD, Medoff BD. Adiponectin decreases pulmonary arterial remodeling in murine models of pulmonary hypertension. Am J Respir Cell Mol Biol 2011;45(2):340-347.
63. Sutherland LN, Capozzi LC, Turchinsky NJ, Bell RC, Wright DC. Time course of high-fat diet-induced reductions in adipose tissue mitochondrial proteins: potential mechanisms and the relationship to glucose intolerance. Am J Physiol Endocrinol Metab 2008;295(5):E1076-E1083.
64. Ribot J, Rodriguez AM, Rodriguez E, Palou A. Adiponectin and resistin response in the onset of obesity in male and female rats. Obesity 2008;16(4):723-730.
65. Kwon EY, Shin SK, Cho YY, Jun UJ, Kim E, Park T, Park JHY, et al. Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose tissue depots during diet-induced obesity. BMC Genomics 2012;13:450.
66. Duval C, Thissen U, Keshtkar S, Accart B, Stienstra R, Boekschoten MV, Roskams T, Kersten S, Muller M. Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57BL/6 mice. Diabetes 2010;59(12):3181-3191.
67. Moral-Sanz J, Menendez C, Moreno L, Moreno E, Cogolludo A, Perez-Vizcaino F. Pulmonary arterial dysfunction in insulin resistant obese Zucker rats. Respir Res 2011;12:51