Targeting of cold-inducible RNA-binding protein alleviates sepsis via alleviating inflammation, apoptosis and oxidative stress in heart.

A systemic inflammatory response is observed in patients undergoing shock and sepsis. This study aimed to explore the effects of cold-inducible RNA-binding protein (CIRP) on sepsis-associated cardiac dysfunction and the underlying mechanism. In vivo and in vitro lipopolysaccharide (LPS)-induced sepsis models were established in mice and neonatal rat cardiomyocytes (NRCMs), respectively. CRIP expressions were increased in the mouse heart and NRCMs treated with LPS. CIRP knockdown alleviated LPS-induced decreases of left ventricular ejection fraction and fractional shortening. CIRP downregulation attenuated the increases of inflammatory factors in the LPS-induced septic mouse heart, and NRCMs. The enhanced oxidative stress in the LPS-induced septic mouse heart and NRCMs was suppressed after CIRP knockdown. By contrast, CIRP overexpression yielded the opposite results. Our current study indicates that the knockdown of CIRP protects against sepsis-induced cardiac dysfunction through alleviating inflammation, apoptosis and oxidative stress of cardiomyocytes.

Honokiol alleviates sepsis-associated cardiac dysfunction via attenuating inflammation, apoptosis and oxidative stress.

OBJECTIVE: Honokiol, a natural active compound extracted from Chinese herbal medicine, can ameliorate acute lung and kidney injury of sepsis. This study was to explore the effects of honokiol on sepsis-associated cardiac dysfunction and the underlying mechanism. METHODS: Septic mice were induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS), and septic HL-1 or AC16 cells were induced by LPS. RESULTS: Honokiol improved the survival and alleviated cardiac dysfunction in mice with CLP-induced sepsis. Honokiol inhibited the increased interleukin (IL) 1-ß, IL-6 and tumour necrosis factor (TNF)-α in the serum and heart of CLP- and LSP-induced septic mice. Honokiol treatment reversed the increased levels of IL1-ß, IL-6 and TNF-α in LPS-induced HL-1 cells. Honokiol treatment also decreased the elevated levels of IL1-ß, IL-6 and TNF-α in LPS-induced AC16 cells. The increased cardiac apoptosis in CLP- and LPS-induced septic mice was alleviated by honokiol. The enhancement of oxidative stress in the heart of CLP- and LPS-induced septic mice was suppressed after honokiol administration. CONCLUSION: These results showed that honokiol could ameliorate sepsis-associated cardiac dysfunction via attenuating inflammation, apoptosis, and oxidative stress. Honokiol is a prospective drug for sepsis-associated heart damage in the future.

Fibroblast growth factor 12 attenuated cardiac remodeling via suppressing oxidative stress.

Fibroblast growth factors (FGFs) mediate key cardiac functions from development to homeostasis and disease. The current research was to explore the effects of FGF12 in the fibrosis of cardiac function and heart failure, and whether FGF12 alleviated cardiac fibrosis via inhibition of oxidative stress. Ligation of left coronary artery in mice induced heart failure and myocardial infarction (MI). Angiotensin II (Ang II) was administered to cardiac fibroblasts (CFs). FGF12 upregulation or FGF12 transgenic (Tg) mice could improve cardiac dysfunction of MI mice, and attenuated cardiac fibrosis of heart failure induced by MI in mice. FGF12 overexpression suppressed the increases of collagen I, collagen III and fibronectin which was induced by Ang II in CFs. The oxidative stress was enhanced in the heart of MI mice and CFs treated with Ang II, and these enhances were attenuated via FGF12 overexpression. Superoxide dismutase (SOD) overexpression inhibited the enhancements of collagen I, collagen III and fibronectin in the heart of MI mice, and in the CFs treated with Ang II. Overexpression of nicotinamide adenine dinucleotide phosphate oxidases (Nox1) reversed the attenuating influences of FGF12 on the enhancements of collagen I, collagen III and fibronectin in the CFs induced by Ang II. These outcomes showed that FGF12 upregulation can improve cardiac dysfunction and heart fibrosis of heart failure. FGF12 attenuates oxidative stress to suppress the cardiac fibrosis.

Trimethylamine N-oxide promotes atherosclerosis via regulating the enriched abundant transcript 1/miR-370-3p/signal transducer and activator of transcription 3/flavin-containing monooxygenase-3 axis.

Atherosclerosis (AS) is one of the main causes of cardiovascular diseases (CVDs). Trimethylamine N-oxide (TMAO) exacerbates the development of AS. This study aimed to investigate the roles of TMAO in AS. In this study, mice were fed with high fat food (HF) and/or injected with TMAO. Oil red O staining was applied for histological analysis. ELISA, qRT-PCR, and Western blot were conducted to determine the TMAO, serum, mRNA, and protein levels. CCK-8, colony formation assay, and flow cytometry assays were performed to detect the functions of human aortic endothelial cells (HUVECs). The results showed that TMAO induced thick internal and external walls and intimal plaques in vivo, and HUVEC dysfunction in vitro. TMAO and lncRNA enriched abundant transcript 1 (NEAT1) were increased in AS clinical samples and TMAO-HUVECs. Downregulated NEAT1 inhibited proliferation and promoted the apoptosis of HUVECs. NEAT1 regulated the expression of signal transducer and activator of transcription 3 (STAT3) via sponging miR-370-3p. Overexpression of miR-370-3p facilitated the effects of NEAT1 on the cellular functions of HUVECs, while STAT3 exerted opposing effects. The activation of STAT3 promoted the expression of flavin-containing monooxygenase-3 (FMO3). Taken together, our results show that TMAO-NEAT1/miR-370-3p/STAT3/FMO3 forms a positive feedback loop to exacerbate the development of AS. This novel feedback loop may be a promising therapeutic target for AS.