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Previous studies have demonstrated that bone morphogenetic proteins (BMPs) play important roles in cardiovascular diseases, including atherosclerosis, artery calcification, myocardial remodeling, pulmonary arterial hypertension, and diabetic cardiomyopathy. Kielin/chordin-like protein (KCP) is a secreted protein that regulates the expression and function of BMPs. However, the role of KCP in cardiac aging remains unknown. In this study, we aimed to investigate the role of KCP in cardiac aging and its possible mechanisms. Echocardiogram showed that heart function was impaired in aged mice (24 months). In addition, analysis of heart structure showed that KCP knockout (KO) aggravated cardiac remodeling in aged mice. Moreover, KCP KO increased p-smad2/3 and TGF-β expression, while decreased BMP-2 expression in aged mice. Furthermore, KCP KO increased the expression of cardiac senescence-related proteins in aged mice. KCP KO aggravated the imbalance of oxidants and antioxidants and increased the expression of proinflammatory cytokines and cardiomyocyte apoptosis in aged mice. Our study demonstrated that KCP KO aggravated cardiac aging in mice by increasing the levels of oxidative stress, inflammation, and cardiomyocyte apoptosis. Key message: KCP KO aggravated aging-related cardiac dysfunction and remodeling in male mice. KCP KO aggravated cardiac aging by increasing the levels of oxidative stress, inflammation, and cardiomyocyte apoptosis. [ABSTRACT FROM AUTHOR]

[Display omitted] 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. 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. 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. IL-27p28 knockdown aggravates DOX-induced cardiac injury by worsening the M1 macrophage/M2 macrophage imbalance and its associated inflammatory response and oxidative stress. [ABSTRACT FROM AUTHOR]

Maresin 1 (MaR1) is a pro-resolving lipid mediator that has been reported to have strong regulatory effects on oxidative stress and inflammation. This study aimed to determine the effect of MaR1 on lipopolysaccharide (LPS)-induced sepsis-related cardiac injury and explore its possible mechanisms. Mice were administered MaR1 or PBS and then treated with LPS or saline for 6 h. Then, cardiac function, cardiac injury markers, cardiac macrophage differentiation, oxidative stress and myocardial cell apoptosis in each group were measured. MaR1 treatment significantly decreased the serum levels of lactate dehydrogenase (LDH) and kinase isoenzyme (CK-MB) and improved cardiac function in LPS-induced mice. Treatment with MaR1 also inhibited LPS-induced M1 macrophage differentiation and reduced M1 macrophage-related cytokine secretion while promoting M2 macrophage differentiation and increasing M2 macrophage-related inflammatory mediator expression. In addition, MaR1 decreased serum malondialdehyde (MDA) levels and increased serum levels of superoxide dismutase (SOD) and glutathione (GSH), as well as cardiac expression of nuclear factor erythroid-2 related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1), in LPS-induced mice. Furthermore, fewer TUNEL-positive cells were observed in the LPS + MaR1 group than in the LPS group. Our experimental results show that MaR1 alleviates cardiac injury and protects against cardiac dysfunction and may be beneficial in reducing sepsis-induced cardiac injury. [ABSTRACT FROM AUTHOR]