Effect of Intensive Atorvastatin Therapy on Periprocedural PTEN Expression in CD4+T Lymphocytes of Patients with Unstable Angina Undergoing Percutaneous Coronary Intervention

Jiangyou Wang, Han Chen, Dan Song, Jian Peng, Xi Su

Abstract


Objectives: To investigate the effects of intensive atorvastatin therapy on PTEN expression by CD4+ T lymphocytes in patients with unstable angina (UA) that received PCI. Methods: All patients with UA were randomly divided into the pretreatment with an intensive atorvastatin (ATV) group (80mg 12h before PCI, with a further 20mg every day after PCI, n = 56) or a conventional (control) group (only 20 mg/day, n = 56). Circulating CD4+ T cells were subsequently obtained prior to PCI and 18–24 h after successful PCI, using a magnetic cell sorting system. Plasma cTnI, CK-MB, hsCRP, IL-10 and TNF-a levels were measured just prior to the PCI and 18–24 h after PCI. PTEN mRNA and protein were determined by Real-time PCR and western blots, respectively. Results: PTEN mRNA and protein were dramatically decreased in ATV group (p < 0.05). In contrast, TNF-α and hsCRP significantly increased following PCI in two groups, with the ATV group being higher than control group (p < 0.05). IL-10 also markedly increased following PCI for the two groups. However, higher values were associated with the ATV group (p < 0.05). Compared to the control group, the incidence of elevated cTnI levels post-PCI was lower in the ATV group( p < 0.05); however, no difference could be found between the two groups regarding the incidence of elevated CK-MB post-PCI (p >0.05). Conclusion: Intensive atorvastatin treatment reduced the post-PCI myocardial inflammatory response in patients with UA, possibly by enhancing PTEN expression in CD4+ T lymphocytes.


Keywords


Unstable angina, Atorvastatin, CD4+ T lymphocytes, PTEN, TNF-, IL-10

Full Text:

Wang 246 pp85-90

References


Nusca A, Melfi R, Patti G, et al. Statin loading before percutaneous coronary intervention: proposed mechanisms and applications. Future Cardiol 2010;6:579-89. DOI:10.2217/fca.10.77.

Patti G, Pasceri V, Colonna G, et al. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol 2007;49:1272-8. DOI:10.1016/j.jacc.2007.02.025.

Di Sciascio G, Patti G, Pasceri V, et al. Efficacy of atorvastatin reload in patients on chronic statin therapy undergoing percutaneous coronary intervention: results of the ARMYDA-RECAPTURE (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) Randomized Trial. J Am Coll Cardiol 2009;54:558-65. DOI:10.1016/j.jacc.2009.05.028

Patti G, Chello M, Pasceri V, et al. Protection from procedural myocardial injury by atorvastatin is associated with lower levels of adhesion molecules after percutaneous coronary intervention: results from the ARMYDA-CAMs (Atorvastatin for Reduction of Myocardial Damage during Angioplasty-Cell Adhesion Molecules) substudy. J Am Coll Cardiol 2006;48:1560-6.

Tanaka T, Soejima H, Hirai N, et al. Comparison of frequency of interferon-gamma-positive CD4+ T cells before and after percutaneous coronary intervention and the effect of statin therapy in patients with stable angina pectoris. Am J Cardiol 2004;93:1547-9. DOI:10.1016/j.jacc.2006.06.061

George J, Shmuel SB, Roth A, et al. L-arginine attenuates lymphocyte activation and anti-oxidized LDL antibody levels in patients undergoing angioplasty. Atherosclerosis 2004;174:323-7.DOI: http://dx.doi.org/10.1016/j.atherosclerosis.2004.01.025

Dumitriu IE, Baruah P, Finlayson CJ, et al. High levels of costimulatory receptors OX40 and 4-1BB characterize CD4+CD28null T cells in patients with acute coronary syndrome. Circ Res 2012;110:857-69. DOI: 10.1161/CIRCRESAHA.111.261933

Gunzl P, Bauer K, Hainzl E, et al. Anti-inflammatory properties of the PI3K pathway are mediated by IL-10/DUSP regulation. J Leukoc Biol 2010;88:1259-1269. DOI:10.1189/jlb.0110001

[Guideline for diagnosis and treatment of patients with unstable angina and non-ST-segment elevation myocardial infarction]. Zhonghua Xin Xue Guan Bing Za Zhi 2007;35:295-304.

Smith SC, Jr., Dove JT, Jacobs AK, et al. ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines)-executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty) endorsed by the Society for Cardiac Angiography and Interventions. Circulation 2001;103:3019-3041.

Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia. Circulation 1994;89: 1545-1556.

Arroyo-Villa I, Bautista-Caro MB, Balsa A, et al. Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity. PLoS One 2012;7:e42189. DOI: 10.1371/journal.pone.0042189

Methe H, Brunner S, Wiegand D, et al. Enhanced T-helper-1 lymphocyte activation patterns in acute coronary syndromes. J Am Coll Cardiol 2005;45:1939-45. DOI:10.1016/j.jacc.2005.03.040

Ke B, Shen XD, Ji H, et al. HO-1-STAT3 axis in mouse liver ischemia/reperfusion injury: regulation of TLR4 innate responses through PI3K/PTEN signaling. J Hepatol 2012;56:359-366. DOI: http://dx.doi.org/10.1016/j.jhep.2011.05.023

Kamo N, Ke B, Busuttil RW, et al. PTEN-mediated Akt/beta-catenin/Foxo1 signaling regulates innate immune responses in mouse liver ischemia/reperfusion injury. Hepatology 2013;57:289-298.

Bu DX, Griffin G, Lichtman AH. Mechanisms for the anti-inflammatory effects of statins. Curr Opin Lipidol 2011;22:165-70.

Weitz-Schmidt G, Welzenbach K, Brinkmann V, et al. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 2001;7:687-92.

Cheng X, Ding Y, Xia C, et al. Atorvastatin modulates Th1/Th2 response in patients with chronic heart failure. J Card Fail 2009;15:158-62. DOI: http://dx.doi.org/10.1016/j.cardfail.2008.10.001

Tawfik MK, Ghattas MH, Abo-Elmatty DM, Abdel-Aziz NA. Atorvastatin restores the balance between pro-inflammatory and anti-inflammatory mediators in rats with acute myocardial infarction. Eur Rev Med Pharmacol Sci 2010;14:499-506.

Kim SA, Choi HC. Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells. Biochem Biophys Res Commun 2012;425:866-72. DOI:10.1016/j.bbrc.2012.07.165

Bluml S, Friedrich M, Lohmeyer T, et al. Loss of phosphatase and tensin homolog (PTEN) in myeloid cells controls inflammatory bone destruction by regulating the osteoclastogenic potential of myeloid cells. Ann Rheum Dis 2013. DOI:10.1136/annrheumdis-2013-203486

Lin CF, Young KC, Bai CH, et al. Blockade of reactive oxygen species and Akt activation is critical for anti-inflammation and growth inhibition of metformin in phosphatase and tensin homolog-deficient RAW264.7 cells. Immunopharmacol Immunotoxicol 2013. DOI:10.3109/08923973.2013.837059

Shewan LG, Coats AJS, Henein M. Requirements for ethical publishing in biomedical journals. International Cardiovascular Forum Journal 2015;2(2). DOI: 10.17987/icfj.v2i1.4




DOI: https://doi.org/10.17987/icfj.v8i0.246

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