Predictor value of the inflammation biomarkers regarding the post-infarction remodeling of myocardium

Aim. To study the trait of the changes of circulating level of pro- and antiinflammatory biomarkers as well as metalloproteinase 8 (MMP-8) in the first 7 days after revascularization in patients with acute myocardial infarction with ST segment elevation (STEMI) for assessment of their prognostic value regarding post-infarction remodeling pattern.

Material and methods. In 113 patients with STEMI which developed in 5 months after angioplasty adaptive myocardium remodeling (AMR) (n=56) or pathological myocardium remodeling (PMR) (n=57), determined by enzyme-linked immunosorbent assay (ELISA) method daily serum concentration of pro-inflammatory ((high sensitive C reactive protein, interleukins (IL) 1, 6, tumor necrosis factor alpha and monocyte chemoattractant protein 1)), anti-inflammatory biomarkers (IL-4, IL-10, IL-33, IL-1 receptor antagonist and heregulin-1beta) аs well as ММР-8 in the first 7 days after myocardium revascularization. According to clinic-demographic indices both groups were comparable. Obtained data have been compared with results of 20 healthy persons (control group).

Results. The dynamics of pro-inflammatory biomarkers did not differ in patients with AMR and PMR after revascularization. It was characterized by a significant biomarker increase at 3-rd day followed by a decline toward 7-th day up to initial level. Among anti-inflammatory biomarkers IL-4 and IL-10 have manifested by a distinct dynamic in concern to myocardial remodeling pattern. In both groups these interleukins decreased after angioplasty, reaching a minimal level at 3-rd day. However, in patients with AMR since 4-th day has been established an increase of serum content of IL-4 and IL-10, their increment being at 7-th day in a range of 52-55% (p<0,05). In patients with PMR the interleukins rise was negligible: 5,7-5,8%. MMP-8 dynamics also has been different in groups and was correlated with dynamics of IL-4 and IL-10. Thus, in patients with AMR its level has fallen since 4-th day up to 7-th day by 46,6%, while in group with PMR metalloproteinase level in this period practically did not change, remaining significantly higher than control by 45-53%.

Conclusion. In our study the serum content of main pro-inflammatory biomarkers (hsCRP, IL-1, IL-6, TNF-ɑ) didn’t differ in the first 7 days after revascularization in patients with adaptive and pathological postinfarction remodeling of myocardium, and thus don’t have predictive value concerning the remodeling pattern. Among anti-inflammatory cytokines dynamics of IL-4 and IL-10 differed in dependence on remodeling pattern. Their significant elevation by 52-55% from 4th up to 7th day after angioplasty was established in patients with adaptive myocardium remodeling, while in PMR their level didn’t change during this period that can emphasize their prognostic value. The character of MMP-8 change is pathogenetically correlated with dynamics of IL-4 and IL-10.

1. Galli A, Lombardi F. Postinfarct left ventricular remodeling: a prevailing cause of heart failure. Cardiology Research and Practice 2016; 2016: Article ID 2579832, 12 pages, doi:10.1155/2016/2579832.

2. French BA, Kramer CM. Mechanisms of post-infarct ventricular remodeling. Drug Discov today Dis Mech. 2007;4(3):185-96. doi: 10.1016/j.ddmec.2007.12.006.

3. Borekci A, Gur M, Turkoglu C, et al. Neutrophil to lymphocyte ration predicts left ventricular remodeling in patients with ST elevation myocardial infarction aafter primary percutaneous coronary intervention. Korean Circ J. 2016;46( 1): 15-22. doi:10.4070/kcj.2016.46.1.15.

4. Pokorney SD, Rodriguez JF, Ortiz JT, et al. Infarct healing is a dynamic process following acute myocardial infarction. J of Cardiovasc Magnetic Resonance. 2012;14:62-72. doi:10.1186/1532-429X-14-62.

5. Westman PC, Lipinski MJ, Luger D, et al. Inflammation as a driver of adverse left ventricular remodeling after acute myocardial infarction. JACC. 2016;67(17):2050-60.

6. Seropian IM, Toldo S, Van Tassell BW, et al. Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. JACC. 2014;63(16):1593-603. doi:10.1016/j.jacc.2014.01.014.

7. Bally M, Dendukuri N, Rich B, et al. Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ. 2017;357:j1909, doi:10.1136/bmj.j190IL-10 cytokine family. Mediators of Inflammation. 2015; http://dx.org/10.1155/2015/764641.

8. Mulvagh S, Quinones M, Kleiman NS, et al. Estimation of Left Ventricular End-Diastolic Pressure From Doppler Transmitral Flow Velocity in Cardiac Patients Independent of Systolic Performance. JAAC. 1992;20(1):112-9.

9. Frangogiannis NG. The inflammatory response in myocardial injury, repair, and remodeling. Nat Rev Cardiol. 2014;11:255-65. doi:101038/nrcardio.2014.28.

10. Ong SB, Hernandez-Resendiz S, Crespo-Alvilan GE, et al. Inflammation following acute myocardial infarction: multiple players, dynamic roles and novel therapeutic opportunities. Pharamacol Therapeut. 2018;186:73-87. doi: 10.1016/j.pharmthera.2018.01.001.

11. Anzai T. Post-infarction inflammation and left ventricular remodeling: a double-edged sword. Circ J. 2013;77:580-7. doi:10.1253/circj.CJ-13-0013.

12. Lacraz S, Nicod LP, Chicheportiche R, et al. IL-10 inhibits metalloproteinase and stimulates TIMP-1 production in human mononuclear phagocytes. J Clin Invest. 1995;96(5):2304-10. doi:10.1172/JCI118286.

13. Ridker PM, Thuren T, Zalewski A, Libbi P. Interleukin-13 inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162(4):597-605. doi:10.1016/j.ahj.2011.06.012.