Abstract
Background
Numerous evidence has suggested that either hypertension or atrial fibrillation (AF) is associated with systemic inflammation. Peroxisome proliferator‐activated receptor‐γ (PPARγ) has been proved to have anti‐inflammatory effects and is implicated as a molecular pathway involved in many cardiovascular diseases, such as hypertension. The correlation between PPARγ inflammation and AF is still unknown.
Methods
Using a case‐control study design, 57 patients with hypertensive AF (persistent AF: 32, paroxysmal AF: 25) were included into the study groups. A total of 32 age‐matched patients with hypertension, but without AF were selected as the control group. The expressions of PPARγ, interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) mRNA in monocytes were detected by using a reverse transcription‐polymerase chain reaction (RT‐PCR). Interleukin‐1 (IL‐1) was measured by immunoenzymetric methods.
Results
The PPARγ mRNA was markedly decreased in the hypertensive AF group as compared with the hypertensive non‐AF group, and it was significantly lower in persistent AF than paroxysmal AF (0.222 ± 0.0702 vs 0.564 ± 0.0436, P<0.01). TNF‐α mRNA, IL‐6 mRNA, and IL‐1 were increased in patients with hypertensive AF compared to the non‐AF group and it was even higher in persistent AF than in paroxysmal AF (0.721 ± 0.0541 vs 0.530 ± 0.0496, 0.567 ± 0.044 vs 0.457 ± 0.0505, 325.61 ± 88.10 vs 190.65 ± 59.38, respectively, P<0.01). TNF‐α, IL‐6, and IL‐1 were in negative correlation with PPARγ, the correlation coefficient was − 0.854, − 0.769, and − 0.702, respectively (P<0.01).
Conclusions
In hypertensive patients, increased inflammatory cytokines were associated with increased incidence of AF and atrial remodeling; PPARγ may be involved in the pathogenesis of AF by regulation of inflammation. Copyright © 2009 Wiley Periodicals, Inc.
Full Text
The Full Text of this article is available as a PDF (253.8 KB).
References
- 1. Karthikeyan VJ, Lip GY. White blood cell count and hypertension. J Hum Hypertens 2006; 20: 310–312. [DOI] [PubMed] [Google Scholar]
- 2. Bautista LE, Vera LM, Arenas IA, et al. Independent association between inflammatory markers (C‐reactive protein, interleukin‐6, and TNF‐α) and essential hypertension. J Hum Hypertens 2005; 19: 149–154. [DOI] [PubMed] [Google Scholar]
- 3. Psychari SN, Apostolou TS, Sinos L, et al. Relation of elevated C‐reactive protein and interleukin‐6 levels to left atrial size and duration of episodes in patients with atrial fibrillation. Am J Cardiol 2005; 95: 764–767. [DOI] [PubMed] [Google Scholar]
- 4. Sata N, Hamada N, Horinouchi T, et al. C‐reactive protein and atrial fibrillation: is inflammation a consequence or a cause of atrial fibrillation? Jpn Heart J 2004; 45: 441–445. [DOI] [PubMed] [Google Scholar]
- 5. Bruins P, te Velthuis H, Yazdanbakhsh AP, et al. Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C‐reactive protein and is associated with postoperative arrhythmia. Circulation 1997; 96: 3542–3548. [DOI] [PubMed] [Google Scholar]
- 6. Gedikli O, Dogan A, Altuntas I, et al. Inflammatory markers according to types of atrial fibrillation. Int J Cardiol 2007; 120: 193–197. [DOI] [PubMed] [Google Scholar]
- 7. Chung MK, Martin DO, Sprecher D, et al. C‐reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001; 104: 2886–2891. [DOI] [PubMed] [Google Scholar]
- 8. Frustaci A, Chimenti C, Bellocci F, et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 1997; 96: 1180–1184. [DOI] [PubMed] [Google Scholar]
- 9. Fajas L, Auboeuf D, Raspe E, et al. The organization, promoter analysis, and expression of the human PPARγ gene. J Biol Chem 1997; 272: 18779–18789. [DOI] [PubMed] [Google Scholar]
- 10. Ricote M, Huang J, Fajas L, et al. Expression of the peroxisome proliferator‐activated receptor‐γ (PPARγ ) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci USA 1998; 95: 7614–7619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Benson S, Wu J, Padmanabhan S, et al. Peroxisome proliferator‐activated receptor (PPAR)‐γ expression in human vascular smooth muscle cells: inhibition of growth, migration, and c‐fos expression by the peroxisome proliferator‐activated receptor (PPAR)‐γ activator troglitazone. Am J Hypertens 2000; 13: 74–82. [DOI] [PubMed] [Google Scholar]
- 12. Mehrabi MR, Thalhammer T, Haslmayer P, et al. The peroxisome proliferator‐activated receptor gamma (PPARγ ) is highly expressed in human heart ventricles. Biomed Pharmacother 2002; 56: 407–410. [DOI] [PubMed] [Google Scholar]
- 13. Babaev VR, Yancey PG, Ryzhov SV, et al. Conditional knockout of macrophage PPAR[γ] increases atherosclerosis in C57BL/6 and low‐density lipoprotein receptor‐deficient mice. Arterioscler Thromb Vasc Biol 2005; 25: 1647–1653. [DOI] [PubMed] [Google Scholar]
- 14. Midaoui A, Wu LY, Wang R, et al. Modulation of cardiac and aortic peroxisome proliferator‐activated receptor‐γ expression by oxidative stress in chronically glucose‐fed rats. Am J Hypertens 2006; 19: 407–412. [DOI] [PubMed] [Google Scholar]
- 15. Vamecq J, Latruffe N. Medical significance of peroxisome proliferator‐ activated receptors. Lancet 1999; 354: 141–148. [DOI] [PubMed] [Google Scholar]
- 16. Tao L, Liu HR, Gao E, et al. Antioxidative, antinitrative, and vasculoprotective effects of aperoxisome proliferator‐activated receptor agonist in hypercholesterolemia. Circulation 2003; 108: 2805–2811. [DOI] [PubMed] [Google Scholar]
- 17. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines: developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114: 257–354. [DOI] [PubMed] [Google Scholar]
- 18. Jiang C, Ting AT, Seed B. PPAR‐γ agonists inhibit production of monocyte inflammatory cytokines. Nature 1998; 391: 82–86. [DOI] [PubMed] [Google Scholar]
- 19. Kostin S, Klein G, Szalay Z, et al. Structural correlate of atrial fibrillation in human patients. Cardiovasc Res 2002; 54: 361–379. [DOI] [PubMed] [Google Scholar]
- 20. Schotten U, Ausma J, Stellbrink C, et al. Cellular mechanisms of depressed atrial contractility in patients with chronic atrial fibrillation. Circulation 2001; 103: 691–698. [DOI] [PubMed] [Google Scholar]
- 21. Healey JS, Baranchuk A, Crystal E, et al. Prevention of atrial fibrillation with angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers: a meta‐analysis. J Am Coll Cardiol 2005; 45: 1832–1839. [DOI] [PubMed] [Google Scholar]
- 22. Murray KT, Rottman JN, Arbogast PG, et al. the AFFIRM Investigators. Inhibition of angiotensin II signaling and recurrence of atrial fibrillation in AFFIRM. Heart Rhythm 2004; 1(6): 669–675. [DOI] [PubMed] [Google Scholar]
- 23. Ducharme A, Swedberg K, Pfeffer MA, et al. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. Am Heart J 2006; 152: 86–92. [PubMed] [Google Scholar]
- 24. Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long‐lasting persistent atrial fibrillation: a prospective and randomized study. Circulation 2002; 106: 331–336. [DOI] [PubMed] [Google Scholar]