Radiation‐induced heart disease (RIHD) is a prevalent cardiovascular complication of radiation therapy, with coronary heart disease being the most common manifestation. Clinical presentations of RIHD vary and may include conduction abnormalities, ischemic heart disease, cardiomyopathy, heart failure, and valvular damage. Even low doses of radiation significantly increase the risk of cardiovascular disease, often associated with severe stenosis detected via angiography. Radiation‐induced damage to the cardiac endothelium triggers inflammatory responses and oxidative stress, which contribute to the progression of atherosclerosis. This study explores how radiation activates multiple signaling pathways through the generation of reactive oxygen species, resulting in vascular endothelial damage, cellular senescence, inflammatory responses, and DNA damage. It further examines the impact of radiation on vascular integrity and tight junction proteins, leading to increased vascular permeability and infiltration by inflammatory cells. From a clinical perspective, we emphasize the challenges posed by the coexistence of tumors in many patients with RIHD, as tumors complicate the microenvironment and may have mutually reinforcing interactions with radiation‐induced damage. We also discuss various therapeutic strategies, including novel approaches targeting cellular senescence and immune responses, with a focus on the potential use of navitoclax and IL‐6 (interleukin‐6) inhibitors to prevent irreversible cardiomyocyte fibrosis and ongoing vascular damage. In conclusion, RIHD is a multifaceted disease involving complex biological processes and signaling pathways. Early intervention and targeted therapies are crucial for improving patient outcomes. Future research should prioritize uncovering the molecular mechanisms of RIHD and developing more effective therapeutic strategies.

Exposure to medium and high doses of ionizing radiation (IR) can induce long-term bone marrow (BM) suppression. We previously showed that recombinant human thrombopoietin (rhTPO) significantly promotes recovery from hematopoietic-acute radiation syndrome, but its effect on long-term BM suppression remains unknown. C57BL/6 mice were exposed to 6.5 Gy γ-rays of total body irradiation (TBI) at a dose-rate of 63.01 cGy per minute, and the mice were treated with rhTPO (100 μg; intramuscular injection) or vehicle at 2 h after TBI. All mice were killed one or two months after TBI for analysis of peripheral blood cell counts, long-term hematopoietic stem cell (HSC) frequency, and BM-derived clonogenic activity. The HSC self-renewal capacity was analyzed by BM transplantation. The levels of reactive oxygen species (ROS) production and ratios of γH2AX+ and p16, p53, and p21 mRNA in HSCs were measured by flow cytometry and real-time polymerase chain reaction, respectively. Treatment with rhTPO reduced long-term myelosuppression by improving long-term hematopoietic reconstitution (p < 0.05) after transplantation and resting state maintenance of HSCs (p < 0.05). Moreover, rhTPO treatment was associated with a sustained reduction in long-term ROS production, reduction of long-term DNA damage, diminished p53/p21 mRNA expression, and prevention of senescence after TBI. This study suggests rhTPO is an effective agent for treating IR-induced long-term BM injury because it regulates hematopoietic remodeling and HSC cycle disorder through the ROS/p53/p21/p16 pathway long term after IR.

Ionizing radiation (IR)-induced hematopoietic injury has become a global concern in the past decade. The underlying cause of this condition is a compromised hematopoietic reserve, and this kind of hematopoietic injury could result in infection or bleeding, in addition to lethal mishaps. Therefore, developing an effective treatment for this condition is imperative. Fluacrypyrim (FAPM) is a recognized effective inhibitor of STAT3, which exhibits anti-inflammation and anti-tumor effects in hematopoietic disorders. In this context, the present study aimed to determine whether FAPM could serve as a curative agent in hematopoietic-acute radiation syndrome (H-ARS) after total body irradiation (TBI). The results revealed that the peritoneally injection of FAPM could effectively promote mice survival after lethal dose irradiation. In addition, promising recovery of peripheral blood, bone marrow (BM) cell counts, hematopoietic stem cell (HSC) cellularity, BM colony-forming ability, and HSC reconstituting ability upon FAPM treatment after sublethal dose irradiation was noted. Furthermore, FAPM could reduce IR-induced apoptosis in hematopoietic stem and progenitor cells (HSPCs) both in vitro and in vivo. Specifically, FAPM could downregulate the expressions of p53-PUMA pathway target genes, such as Puma, Bax, and Noxa. These results suggested that FAPM played a protective role in IR-induced hematopoietic damage and that the possible underlying mechanism was the modulation of apoptotic activities in HSCs.

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which enhanced platelet destruction and impaired platelet production coexist, and a substantial proportion of patients remain refractory to available therapies. Here, we evaluated 2B9-Fc, a thrombopoietin (TPO) mimetic peptide engineered from a cyclic peptide with high affinity for both human and mouse c-MPL, in passive (anti-CD41 monoclonal antibody R300) and active (guinea pig anti-mouse platelet serum, GP-APS) immunization male C57BL/6J and humanized c-MPL receptor transgenic mouse models of ITP. 2B9-Fc (500 μg/kg, subcutaneously) significantly elevated peripheral platelet counts in both models (p < 0.01), without affecting WBC, RBC, or hemoglobin, and alleviated skin purpura and bleeding scores in the active model. In addition, 2B9-Fc treatment was associated with a reduced splenic M1/M2 macrophage ratio, increased regulatory T cells (Tregs), downregulated IL-6 and iNOS while upregulating TGF-β1 and Foxp3, and suppressed STAT1 phosphorylation. In humanized c-MPL receptor transgenic (MT) mice, 2B9-Fc promoted CD41⁺ megakaryocyte generation in vitro and sustained platelet recovery in vivo through day 14. These results indicate that 2B9-Fc ameliorates ITP and is associated with promotion of megakaryocyte maturation and restoration of immune tolerance, likely involving inhibition of STAT1-mediated M1 polarization and Treg expansion, supporting its potential for clinical translation.