Elevated circulating level of P2X7 receptor is related to severity of coronary artery stenosis and prognosis of acute myocardial infarction
Abstract
Background: Acute myocardial infarction (AMI) is a severely life-threatening cardiovascular disease. Previous research has identified an association between the P2X7 receptor (P2X7R) and the development of atherosclerosis. However, the correlation of its expression with the clinical prognosis of patients with AMI remains unclear. The present study aimed to investigate the potential role of P2X7R in Chinese patients with AMI.
Methods: Seventy-nine patients with AMI and 48 controls were consecutively enrolled in this prospective observational study. Circulating P2X7R mRNA expression levels and other clinical variables were determined upon admission to the hospital. Patients were followed up for 360 days, and the end-point was considered as the occurrence of major adverse cardiovascular events (MACE).
Results: Circulating P2X7R mRNA expression level in peripheral blood mononuclear cells of patients with AMI were significantly higher than those in controls and had promising diagnostic ability of AMI with an area under the curve of 0.928. Furthermore, P2X7R was demonstrated to be correlated positively with the severity of coronary artery stenosis. Additionally, this is the first study to indicate that higher P2X7R mRNA expression is associated with a higher rate of MACE within 360 days after AMI.
Conclusions: The present study showed that the circulating level of P2X7R was elevated in AMI patients and was closely associated with the severity of coronary artery stenosis and prognosis of AMI.
Keywords: P2X7Racute myocardial infarctioncoronary artery stenosisprognosis
References
- Packard R, Lichtman A, Libby P. Innate and adaptive immunity in atherosclerosis. Sem Immunopathol. 2009; 31(1): 5–22.
- Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005; 352(16): 1685–1695.
- Newby AC, George SJ, Ismail Y, et al. Vulnerable atherosclerotic plaque metalloproteinases and foam cell phenotypes. Thromb Haemost. 2009; 101(6): 1006–1011.
- Baroja-Mazo A, Pelegrín P. Modulating P2X7 receptor signaling during rheumatoid arthritis: new therapeutic approaches for bisphosphonates. J Osteoporos. 2012; 2012: 408242.
- Piscopiello M, Sessa M, Anzalone N, et al. P2X7 receptor is expressed in human vessels and might play a role in atherosclerosis. Int J Cardiol. 2013; 168(3): 2863–2866.
- Peng K, Liu L, Wei D, et al. P2X7R is involved in the progression of atherosclerosis by promoting NLRP3 inflammasome activation. Int J Mol Med. 2015; 35(5): 1179–1188.
- Labasi JM, Petrushova N, Donovan C, et al. Absence of the P2X7 receptor alters leukocyte function and attenuates an inflammatory response. J Immunol. 2002; 168(12): 6436–6445.
- Savio L, Mello Pd, Silva Cda, et al. The P2X7 receptor in inflammatory diseases: angel or demon? Front Pharmacol. 2018; 9.
- Burnstock G. Purinergic signaling in the cardiovascular system. Circulation Research. 2017; 120(1): 207–228.
- Mariathasan S, Weiss DS, Newton K, et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 2006; 440(7081): 228–232.
- Lin Lu, Huang S, Zhu Z, et al. P2X7 receptor regulates EMMPRIN and MMP‑9 expression through AMPK/MAPK signaling in PMA‑induced macrophages. Mol Med Rep. 2018; 18(3): 3027–3033.
- Stachon P, Heidenreich A, Merz J, et al. P2X deficiency blocks lesional inflammasome activity and ameliorates atherosclerosis in mice. Circulation. 2017; 135(25): 2524–2533.
- Yin J, Wang Yu, Hu H, et al. P2X receptor inhibition attenuated sympathetic nerve sprouting after myocardial infarction via the NLRP3/IL-1β pathway. J Cell Mol Med. 2017; 21(11): 2695–2710.
- Du D, Jiang M, Liu M, et al. Microglial P2X₇ receptor in the hypothalamic paraventricular nuclei contributes to sympathoexcitatory responses in acute myocardial infarction rat. Neurosci Lett. 2015; 587: 22–28.
- Tu G, Zou L, Liu S, et al. Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia. Purinergic Signal. 2016; 12(3): 521–535.
- Kaptoge S, Di Angelantonio E, Lowe G, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010; 375(9709): 132–140.
- Pokharel Y, Sharma PP, Qintar M, et al. High-sensitivity C-reactive protein levels and health status outcomes after myocardial infarction. Atherosclerosis. 2017; 266: 16–23.
- Giuliani AL, Berchan M, Sanz JM, et al. The P2X7 receptor is shed into circulation: correlation with c-reactive protein levels. Front Immunol. 2019; 10: 793.
