Doxorubicin induced immune abnormalities and inflammatory responses via HMGB1, HIF1-α and VEGF pathway in progressive of cardiovascular damage

Ahmad Syukri; Budu; Mochammad Hatta; Muzakkir Amir; Mohammad Saifur Rohman; Idar Mappangara; Cahyono Kaelan; Siti Wahyuni; Agussalim Bukhari; Ade Rifka Junita; Muhammad Reza Primaguna; Ressy Dwiyanti; Andini Febrianti

doi:10.1016/j.amsu.2022.103501

Doxorubicin induced immune abnormalities and inflammatory responses via HMGB1, HIF1-α and VEGF pathway in progressive of cardiovascular damage

Ann Med Surg (Lond). 2022 Mar 21:76:103501. doi: 10.1016/j.amsu.2022.103501. eCollection 2022 Apr.

Authors

Ahmad Syukri^{1

2}, Budu³, Mochammad Hatta², Muzakkir Amir⁴, Mohammad Saifur Rohman⁵, Idar Mappangara⁴, Cahyono Kaelan⁶, Siti Wahyuni⁷, Agussalim Bukhari⁸, Ade Rifka Junita^{1

2}, Muhammad Reza Primaguna⁹, Ressy Dwiyanti^{10

11}, Andini Febrianti¹¹

Affiliations

¹ Post Graduate School. Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
² Molecular Biology and Immunology Laboratory, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
³ Department of Ophthalmology, Faculty of Medicine Hasanuddin University, Makassar, Indonesia.
⁴ Department Cardiology and Vascular Medicine, Faculty of Medicine Hasanuddin University, Makassar, Indonesia.
⁵ Department of Cardiology and Vascular Medicine, Faculty of Medicine, Saiful Anwar General Hospital, Brawijaya University, Malang, East Java, Indonesia.
⁶ Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
⁷ Department of Parasitology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
⁸ Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
⁹ Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
¹⁰ Department of Medical Microbiology, Faculty of Medicine, Tadulako University, Palu, Indonesia.
¹¹ Department of Forensic and Medicolegal, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.

Abstract

Background: Doxorubicin (DOX) is a commonly used treatment for cancer and the mechanism of DOX-induced cardiomyocyte damage in cardiovascular disease is not fully understood. High-mobility group box 1 (HMGB1), strong induce proinflammatory cytokines via damage associated molecular pattern (DAMP) which its interaction with the receptor of advanced glycation end products (RAGE), that affect cytokine release, and angiogenesis via the role of HMBG1, HIF-1α and VEGF as an important regulator in these cardiac failure processes. Hypoxia-inducible factor-1α (HIF-1α) is plays an important role in the cellular response to systemic oxygen levels of cells and VEGF is an angiogenic factor and can stimulate cellular responses on the surface of endothelial cells will be described.

Objective: The aim of this article is to comprehensively review the role of HMGB1, HIF-1α, and VEGF in DOX-induced Cardiovascular Disease and its molecular mechanisms.

Methods: The data in this study were collect by search the keyword combinations of medical subject headings (MeSH) of "HMGB1", "HIF-1 α", "VEGF", "DOX" and "Cardiovascular disease" and relevant reference lists were manually searched in PubMed, EMBASE and Scopus database. All relevant articles in data base above were included and narratively discussed in this review article.

Results: Several articles were revealed that molecular mechanisms of the DOX in cardiomyocyte damage and related to HMGB1, HIF-1α and VEGF and may potential treatment and prevention to cardiovascular disease in DOX intervention.

Conclusion: HMGB1, HIF-1α and VEGF has a pivotal regulator in DOX-induce cardiomyocyte damage and predominantly acts through different pathways. The role of HMGB1 in DOX-induced myocardial damage suggests that HMGB1 is a mediator of DOX-induced damage. In addition, DOX can inhibit HIF-1α activity where DOX can decrease HIF-1α expression and HIF-1α is also responsible for upregulation of several angiogenic factors, including VEGF. VEGF plays an important role in angiogenesis and anti-angiogenesis both in vitro and in vivo and reduces the side effects of DOX markedly. In addition, the administration of anti-angiogenesis will show an inhibitory effect on angiogenesis mediated by the VEGF signaling pathway and triggered by DOX in cells.

Keywords: Cardiotoxicity; Cardiovascular disease; DOX; HIF-1α; HMGB1; VEGF.

Publication types

Review