Prevention of MI-Induced Heart Failure by PEGylated Graphene Quantum Dot Nanomaterials and Anti-BMP1.3 Monoclonal Antibody Treatments
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.
- 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.
- 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
- 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
- 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