Delayed Percutaneous Coronary Intervention Regulates MMP-9, NOX2, and TGF-β1 After ST-Segment Elevation Myocardial Infarction: A Quasi-Experimental Study
Abstract
Background: Primary percutaneous coronary intervention (PCI) remains the main treatment for patients with ST-segment elevation myocardial infarction (STEMI). Nonetheless, many patients still miss the primary PCI golden period or refuse it, especially in developing countries, such as Indonesia. This study compared the effects of delayed PCI (12–48 hours after STEMI onset) and optimal medical therapy (OMT) on cardiac remodeling biomarkers matrix metalloproteinase-9 (MMP-9), nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), and transforming growth factor-β1 (TGF-β1).
Methods: This quasi-experimental study enrolled 55 patients with STEMI. Initially, all participants were advised to undergo delayed PCI. Patients who agreed to receive delayed PCI plus OMT were included in group 1 (n=24), and those who refused delayed PCI were included in group 2 and received OMT only. Blood samples were drawn at 24 hours and on day 5 after the intervention. MMP-9, NOX2, and TGF-β1 levels were measured using enzyme-linked immunosorbent assay. Data were analyzed using Stata, version 17.
Results: Group 1 showed significant reductions at 24 hours and day 5 in MMP-9 (Cohen d: −0.97, P<0.01 and −0.91, P<0.01, respectively), TGF-β1 (Cohen d: −0.64, P=.01 and −0.73, P<0.01, respectively), and NOX2 (Cohen d: −0.68, P=0.04 and −0.37, P=0.04, respectively) compared with group 2. No significant difference was observed between 24 hours and day 5 within each intervention group.
Conclusion: Delayed PCI performed within 12–48 hours was associated with significantly lower circulating levels of MMP 9, NOX2, and TGF β1 at 24 hours and 5 days compared with OMT alone in STEMI patients with stable conditions.
2. Chinese Society of Cardiology of Chinese Medical Association, Editorial Board of Chinese Journal of Cardiology. [2019 Chinese Society of Cardiology (CSC) guidelines for the diagnosis and management of patients with ST-segment elevation myocardial infarction]. Zhonghua Xin Xue Guan Bing Za Zhi. 2019 Oct 24;47(10).
3. McDermott K, Maynard C, Trivedi R, Lowy E, Fihn S. Factors associated with presenting >12 hours after symptom onset of acute myocardial infarction among Veteran men. BMC Cardiovasc Disord. 2012 Sep 28;12:82.
4. Kim BW, Cha KS, Park MJ, Choi JH, Yun EY, Park JS, et al. The impact of transferring patients with ST-segment elevation myocardial infarction to percutaneous coronary intervention-capable hospitals on clinical outcomes. Cardiol J. 2016 Jun 30;23(3):289-95.
5. Xiu WJ, Yang HT, Zheng YY, Ma YT, Xie X. Delayed PCI 12 Hours after the Onset of Symptoms Is Associated with Improved Outcomes for Patients with ST-Segment Elevation Myocardial Infarction: A Real-World Study. J Interv Cardiol. 2019; 2019:2387929.
6. Xu W, Holmes DN, Becker RC, Roe MT, Peterson ED, Wang TY. Comparison of long-term outcomes between older Asian and white patients with non–ST-segment elevation myocardial infarction: Findings from CRUSADE-CMS database. Am Heart J. 2013 Dec;166(6):1050-5.
7. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-826.
8. DeLeon-Pennell KY, Meschiari CA, Jung M, Lindsey ML. Matrix Metalloproteinases in Myocardial Infarction and Heart Failure. Prog Mol Biol Transl Sci. 2017;147:75-100.
9. Bostan MM, Stătescu C, Anghel L, Șerban IL, Cojocaru E, Sascău R. Post-myocardial infarction ventricular remodeling biomarkers—the key link between pathophysiology and clinic. Biomolecules. MDPI AG; 2020. p. 1–22.
10. Rodrigues KE, Pontes MHB, Cantão MBS, Prado AF. The role of matrix metalloproteinase-9 in cardiac remodeling and dysfunction and as a possible blood biomarker in heart failure. Pharmacol Res. 2024 Aug;206:107285.
11. Bostan MM, Stătescu C, Anghel L, Șerban IL, Cojocaru E, Sascău R. Post-Myocardial Infarction Ventricular Remodeling Biomarkers-The Key Link between Pathophysiology and Clinic. Biomolecules. 2020 Nov 23;10(11).
12. Iyer RP, Jung M, Lindsey ML. MMP-9 signaling in the left ventricle following myocardial infarction. American Journal of Physiology-Heart and Circulatory Physiology. 2016 Jul 1;311(1):H190-8.
13. Liu Y, Wu Z, jin X, Ji M, Huang T, Meng P, et al. NADPH oxidase 2 inhibitor GSK2795039 prevents against cardiac remodeling after MI through reducing oxidative stress and mitochondrial dysfunction. Eur J Pharmacol. 2025 Jun;997:177483.
14. Sirker A, Murdoch CE, Protti A, Sawyer GJ, Santos CXC, Martin D, et al. Cell-specific effects of Nox2 on the acute and chronic response to myocardial infarction. J Mol Cell Cardiol. 2016 Sep;98:11–7.
15. Saadat S, Noureddini M, Mahjoubin-Tehran M, Nazemi S, Shojaie L, Aschner M, et al. Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players. Front Cardiovasc Med. 2021 Jan 25;7.
16. Frangogiannis NG. TGF-β as a therapeutic target in the infarcted and failing heart: cellular mechanisms, challenges, and opportunities. Expert Opin Ther Targets. 2024 Feb 19;28(1-2):45-56.
| Files | ||
| Issue | Vol 21 No 3 (2026) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/rhythm.v21i3.22564 | |
| Keywords | ||
| Matrix Metalloproteinase-9 (MMP-9) Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 (NOX2) Primary percutaneous coronary intervention (PCI) ST-Segment Elevation Myocardial Infarction (STEMI) Transforming Growth Factor-β1 (TGF-β1) | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |

