IL-23p19 deficiency reduces M1 macrophage polarization and improves stress-induced cardiac remodeling by alleviating macrophage ferroptosis in mice.

BACKGROUND: Interleukin-23p19 (IL-23p19) has been demonstrated to be involved in the occurrence and development of cardiovascular diseases such as myocardial infarction and atherosclerosis. This study aimed to examine whether IL-23p19 regulates cardiac remodeling processes and explore its possible mechanisms. METHODS AND RESULTS: Transverse aortic constriction was performed to construct a mouse cardiac remodeling model, and sham surgery was used as a control. The results showed that IL-23p19 expression was increased in the heart after surgery and may be mainly produced by cardiac macrophages. Knockout of IL-23p19 attenuated M1 macrophage polarization, reduced ferroptosis, improved the process of cardiac remodeling and alleviated cardiac dysfunction in TAC mice. Cell culture experiments found that macrophages were the main cause of ferroptosis when phenylephrine (PE) was added, and blocking ferroptosis with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, significantly inhibited M1 macrophage polarization. Treatment with Fer-1 also improved cardiac remodeling and alleviated cardiac dysfunction in IL-23p19-/- mice subjected to TAC surgery. Finally, TAC IL-23p19-/- mice that were administered macrophages isolated from WT mice exhibited an increased proportion of M1 macrophages and aggravated cardiac remodeling, and these effects were reversed when Fer-1 was administered. CONCLUSION: Knockout of IL-23p19 may attenuate M1 macrophage polarization to improve the cardiac remodeling process by reducing macrophage ferroptosis, and IL-23p19 may be a potential target for the prevention and treatment of cardiac remodeling.

Immune cells and hypertension.

Hypertension is one of the leading causes of death due to target organ injury from cardiovascular disease. Although there are many treatments, only one-sixth of hypertensive patients effectively control their blood pressure. Therefore, further understanding the pathogenesis of hypertension is essential for the treatment of hypertension. Much research shows that immune cells play an important role in the pathogenesis of hypertension. Here, we discuss the roles of different immune cells in hypertension. Many immune cells participate in innate and adaptive immune responses, such as monocytes/macrophages, neutrophils, dendritic cells, NK cells, and B and T lymphocytes. Immune cells infiltrate the blood vessels, kidneys, and hearts and cause damage. The mechanism is that immune cells secrete cytokines such as interleukin, interferon, and tumor necrosis factor, which affect the inflammatory reaction, oxidative stress, and kidney sodium water retention, and finally aggravate or reduce the dysfunction, remodeling, and fibrosis of the blood vessel, kidney, and heart to participate in blood pressure regulation. This article reviews the research progress on immune cells and hypertension.

Insights into bone morphogenetic proteins in cardiovascular diseases.

Bone morphogenetic proteins (BMPs) are secretory proteins belonging to the transforming growth factor-ß (TGF-ß) superfamily. These proteins play important roles in embryogenesis, bone morphogenesis, blood vessel remodeling and the development of various organs. In recent years, as research has progressed, BMPs have been found to be closely related to cardiovascular diseases, especially atherosclerosis, vascular calcification, cardiac remodeling, pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT). In this review, we summarized the potential roles and related mechanisms of the BMP family in the cardiovascular system and focused on atherosclerosis and PAH.

IL-27p28 knockout aggravates Doxorubicin-induced cardiotoxicity by regulating Macrophage polarization.

BACKGROUND: Several interleukins (ILs) have been demonstrated to participate in cardiac injury. This study aimed to investigate whether IL-27p28 plays a regulatory role in doxorubicin (DOX)-induced cardiac injury by regulating inflammation and oxidative stress. METHODS: Dox was used to establish a mouse cardiac injury model, and IL-27p28 was knocked out to observe its role in cardiac injury. In addition, monocytes were adoptively transferred to clarify whether monocyte-macrophages mediate the regulatory role of IL-27p28 in DOX-induced cardiac injury. RESULTS: IL-27p28 knockout significantly aggravated DOX-induced cardiac injury and cardiac dysfunction. IL-27p28 knockout also upregulated the phosphorylation levels of p65 and STAT1 and promoted M1 macrophage polarization in DOX-treated mice, which increased cardiac inflammation and oxidative stress. Moreover, IL-27p28-knockout mice that were adoptively transferred WT monocytes exhibited worse cardiac injury and cardiac dysfunction and higher cardiac inflammation and oxidative stress. CONCLUSIONS: IL-27p28 knockdown aggravates DOX-induced cardiac injury by worsening the M1 macrophage/M2 macrophage imbalance and its associated inflammatory response and oxidative stress.