title: Calorie Restriction Attenuates Monocrotaline-induced Pulmonary Arterial Hypertension in Rats.
abstract: Calorie restriction (CR) is one of the most effective nonpharmacological interventions protecting against cardiovascular disease, such as hypertension in the systemic circulation. However, whether CR could attenuate pulmonary arterial hypertension (PAH) is largely unknown. The PAH model was developed by subjecting the rats to a single subcutaneous injection of monocrotaline. CR lowered mean pulmonary arterial pressure (mPAP) and reduced vascular remodeling and right ventricular hypertrophy in PAH rats. Meanwhile, CR attenuated endothelial dysfunction as evidenced by increased relaxation in response to acetylcholine. The beneficial effects of CR were associated with restored sirtuin-1 (SIRT1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation and reduced eNOS acetylation in pulmonary arteries of PAH rats. To further clarify the role of SIRT1 in the protective effects of CR, adenoviral vectors for overexpression of SIRT1 were administered intratracheally at 1 day before monocrotaline injection. Overexpression of SIRT1 exhibited similar beneficial effects on mPAP and endothelial function, and increased eNOS phosphorylation and reduced eNOS acetylation in the absence of CR. Moreover, SIRT1 overexpression attenuated the increase in mPAP in hypoxia-induced PAH animals. Overall, the present data demonstrate that CR may serve as an effective treatment of PAH, and targeting the SIRT1/eNOS pathway may improve treatment of PAH.
authors: Department of Geriatrics, Xi'an Central Hospital; Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
authors: Mingge
authors: M
authors: Ding
authors: Jingyi
authors: J
authors: Lei
authors: Yinxian
authors: Y
authors: Qu
authors: Huan
authors: H
authors: Zhang
authors: Weichuan
authors: W
authors: Xin
authors: Feng
authors: F
authors: Ma
authors: Shuwen
authors: S
authors: Liu
authors: Zhichao
authors: Z
authors: Li
authors: Faguang
authors: F
authors: Jin
authors: Enqing
authors: E
authors: Fu
mesh_terms: D000107:Acetylation; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D031204:Caloric Restriction; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology; D005822:Genetic Vectors; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D016686:Monocrotaline; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D066253:Vascular Remodeling; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; D016686:Monocrotaline; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
references: J Biol Chem. 2009 Jan 16;284(3):1718-24
references: 18990685
references: Nutrition. 1989 May-Jun;5(3):155-71; discussion 172
references: 2520283
references: J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S20-31
references: 19555855
references: Hypertension. 2009 Sep;54(3):668-75
references: 19597040
references: J Pharmacol Exp Ther. 2010 Feb;332(2):455-62
references: 19915069
references: Am J Physiol Endocrinol Metab. 2010 Jun;298(6):E1131-9
references: 20215577
references: Aging Cell. 2010 Jun;9(3):304-12
references: 20121721
references: Am J Respir Crit Care Med. 2010 Jul 15;182(2):261-8
references: 20339146
references: Hypertension. 2010 Sep;56(3):412-21
references: 20696994
references: Am J Respir Crit Care Med. 2010 Sep 1;182(5):652-60
references: 20508210
references: Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2205-11
references: 20705918
references: Antioxid Redox Signal. 2011 Jan 15;14(2):275-87
references: 20518700
references: Mayo Clin Proc. 2011 Feb;86(2):105-12
references: 21282484
references: Expert Rev Respir Med. 2011 Apr;5(2):163-71
references: 21510727
references: Circ Res. 2011 Sep 2;109(6):639-48
references: 21778425
references: Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1205-19
references: 21841020
references: Eur Respir Rev. 2012 Dec 1;21(126):267-70
references: 23204116
references: Respir Med. 2013 Jan;107(1):139-46
references: 23199841
references: Diabetes Care. 2013 Mar;36(3):e32-3
references: 23431096
references: Annu Rev Med. 1997;48:489-509
references: 9046979
references: J Nutr. 1997 Apr;127(4):655-60
references: 9109619
references: J Am Coll Cardiol. 2006 Jan 17;47(2):398-402
references: 16412867
references: J Cardiovasc Pharmacol. 2013 Jun;61(6):513-9
references: 23429595
references: Biochim Biophys Acta. 2013 Oct;1830(10):4820-7
references: 23800577
references: Am J Respir Crit Care Med. 2013 Sep 15;188(6):639-46
references: 23822809
references: Free Radic Biol Med. 2014 Apr;69:198-207
references: 24440469
references: Pulm Pharmacol Ther. 2014 Jun;28(1):17-24
references: 24269521
references: Br J Pharmacol. 2014 Jun;171(12):2964-92
references: 24611611
references: Am J Physiol Lung Cell Mol Physiol. 2014 Jun 1;306(11):L996-L1005
references: 24705719
references: Exp Gerontol. 2007 Aug;42(8):709-12
references: 17482403
references: Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H1120-8
references: 16980338
references: J Cardiovasc Pharmacol. 2015 Jan;65(1):22-7
references: 25162436
references: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14855-60
references: 17785417
references: Circulation. 2007 Dec 11;116(24):2809-17
references: 18040027
references: Chest. 2008 Mar;133(3):789-92
references: 18321907
references: Chest. 2008 Sep;134(3):670; author reply 670-1
references: 18779208
references: Arch Pathol Lab Med. 2008 Sep;132(9):1397-404
references: 18788850
references: Am J Cardiol. 2013 Apr 16;111(8 Suppl):10C-5C
references: 23558024
references: Int J Med Sci. 2013;10(6):771-81
references: 23630443
references: PLoS One. 2013;8(5):e60850
references: 23667430
references: Diabetes. 2009 Feb;58(2):344-51
references: 19008341
references: Metabolism. 1978 Dec;27(12):1711-4
references: 723627
references: Am J Physiol Heart Circ Physiol. 2000 Oct;279(4):H1786-95
references: 11009465
references: Am J Respir Cell Mol Biol. 2000 Dec;23(6):762-71
references: 11104729
references: Circulation. 2001 Aug 21;104(8):945-50
references: 11514384
references: Am J Respir Cell Mol Biol. 2003 Oct;29(4):449-57
references: 12714372