Kaycee Nguyen

Introduction: Ischemic heart disease is the leading cause of deaths in the world¹, and 50 million patients suffer from myocardial infarction (MI) annually. ² Without adequate treatment, MI can result in lost myocardium with subsequent deterioration of heart function, predisposing patients to develop heart failure (HF). Physiological processes that predispose a patient with MI to develop HF include oxidative damage and excessive collagen deposition, causing fibrosis and progressive cardiac dysfunction.^3,4 Therapeutic interventions to prevent disease progression and damage following MI with inadequate delayed revascularization have remained limited. Polyethylene glycol-graphene quantum dots (GQDs-PEG) nanomaterials possess antioxidant activity. Therefore, GQDs-PEG treatment was hypothesized to reduce MI-induced cardiac damage. Additionally, since bone morphogenetic protein 1 (BMP1.3) levels are elevated after MI, its inhibition by a monoclonal antibody should reduce cardiac fibrosis. Methods: Rodent models were used to study alteration in cardiac function upon treatment with either GQDs-PEG or anti-BMP1.3 antibodies. Wistar rats were placed into control or treatment groups. Both groups consisted of sham-Veh., MI-Veh., and MI+GQDs-PEG with 5, 10, and 20 mg/kg doses.³ MI was induced by ligating the left anterior descending (LAD) artery. Afterwards, GQDs-PEG was injected intraperitoneally at different doses every other day for two weeks. Hemodynamic indices (SBP, DBP, left ventricular systolic pressure) were evaluated, and levels of oxidant/antioxidant indices were measured in the infarcted area using the ELISA method, including malondialdehyde, superoxide dismutase, glutathione peroxidase (GPX), and total antioxidant capacity (TAC).³ Heart samples were stained with triphenyl tetrazolium chloride to measure the infarct area. To test the effectiveness of anti-BMP1.3 antibodies, MI was induced in mice by ligating the LAD artery. The mice were then administered 150 or 500 μg/kg doses of the antibody. After 2 months, mice hearts underwent histological and morphometric analysis, and cardiac function was monitored by echocardiography.⁴  Results: 10 and 20 mg/kg GQDs-PEG doses significantly decreased infarct size (P < 0.001) and   Conclusion: GQDs-PEG can treat MI injuries by reducing oxidative stress in a dose-dependent manner to better preserve cardiac performance. Anti-BMP1.3 antibodies decrease cardiac fibrosis in mice with MI, suggesting a therapeutic for preserving cardiac function after ischemia.

1. The top 10 causes of death. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. Accessed April 17, 2022.
2. Virani SS, Alonso A, Aparicio HJ, et al. Heart Disease and Stroke Statistics—2021 Update: A Report From the American Heart Association. Circulation. 2021;143(8). doi:10.1161/cir.0000000000000950
3. Rostamzadeh F, Shadkam-Farrokhi M, Jafarinejad-Farsangi S, Najafipour H, Ansari-Asl Z, Yeganeh-Hajahmadi M. PEGylated Graphene Quantum Dot Improved Cardiac Function in Rats with Myocardial Infarction: Morphological, Oxidative Stress, and Toxicological Evidences. Oxid Med Cell Longev. 2021;2021:8569225. Published 2021 Nov 20. doi:10.1155/2021/8569225
4. Vukicevic S, Colliva A, Kufner V, et al. Bone morphogenetic protein 1.3 inhibition decreases scar formation and supports cardiomyocyte survival after myocardial infarction. Nat Commun. 2022;13(1):81. Published 2022 Jan 10. doi:10.1038/s41467-021-27622-9