The glycocalyx is a complex polysaccharide-protein layer lining the lumen of vascular endothelial cells. Changes in the structure and function of the glycocalyx promote an inflammatory response in blood vessels and play an important role in the pathogenesis of many vascular diseases (e.g., diabetes, atherosclerosis, and sepsis). Vascular endothelial dysfunction is a hallmark of inflammation-related diseases. Endothelial dysfunction can lead to tissue swelling, chronic inflammation, and thrombosis. Therefore, elimination of endothelial inflammation could be a potential target for the treatment of vascular diseases. This review summarizes the key role of the glycocalyx in the inflammatory process and the possible mechanism by which it alleviates this process by interrupting the cycle of endothelial dysfunction and inflammation. Especially, we highlight the roles of different components of the glycocalyx in modulating the inflammatory process, including components that regulate leukocyte rolling, L-selectin binding, inflammasome activation and the signaling interactions between the glycocalyx components and the vascular cells. We discuss how the glycocalyx interferes with the development of inflammation and the importance of preventing glycocalyx impairment. Finally, drawing on current understanding of the role of the glycocalyx in inflammation, we consider a potential strategy for the treatment of vascular diseases.

Mitofusin-2 (Mfn2) is a key outer mitochondrial membrane protein, which maintains normal mitochondrial dynamics and function. However, its role in cardiac fibroblast activation remains poorly understood. In the present study, a rat model of transverse aortic constriction (TAC) was established to observe the cardiac fibroblast activation in vivo. TGF-β1 treatment for 24 hours was used to induce cardiac fibroblast activation in vitro. As a result, the expression of Mfn2 decreased in the hypertrophic heart tissues and cardiac fibroblasts treated with TGF-β1. siMfn2 and adenovirus were applied to mediate Mfn2 gene silencing and overexpression in cardiac fibroblasts to elucidate the relationship between Mfn2 and cardiac fibroblast activation, as well as the possible underlying mechanisms. Knockdown of Mfn2 further promoted TGF-β1-induced cardiac fibroblast activation, while forced expression of Mfn2 attenuated this pathological reaction. The PERK/ATF4 pathway, one of the branches of endoplasmic reticulum (ER) stress, was identified to be involved in this process. Knockdown and overexpression of Mfn2 lead to aggravation or alleviation of the PERK/ATF4 pathway. Blocking this pathway by silencing ATF4 with siATF4 attenuated the pathological process. During the activation of cardiac fibroblasts, knockdown of Mfn2 also increased the production of reactive oxygen species (ROS), while ROS scavenger N-acetyl-l-cysteine (NAC) could attenuate the effect caused by knockdown of Mfn2. Our data suggested that inhibition of Mfn2 could promote cardiac fibroblast activation by activating the PERK/ATF4 signaling pathway and increasing the generation of ROS.

Exosomes are small-membrane vesicles secreted by hematopoietic and malignant epithelial cells as well as trophoblasts. The composition of cancerous exosomes has been proven to play pivotal roles in the maintenance of the microenvironment that is beneficial for the progression of cancer, such as Fas-ligand–triggered lymphocyte apoptosis. We supposed that the immunosuppressive effect of cancerous exosomes might be helpful in the treatment of diseases characterized by overactivation of the immune system and subsequent tissue injury. The aim of this study was to evaluate the protective effect of tumor-derived exosomes in the mice model of lipopolysaccharide (LPS)-induced inflammation. Tetrazolium (MTT) and DNA electrophoresis were used to measure the cytotoxicity of exosomes on lymphocytes. Pathologic observation of tissue sections, serologic analysis of aspartate aminotransferase/alanine aminotransferase (AST/ALT), and urinary analysis of protein were used to assess the protection effect of exosomes in LPS-induced multiorgan damage. In vitro outcomes of MTT and DNA electrophoresis showed the cytotoxicity of exosomes on lymphocytes. Together with the alleviation of organ damages evaluated by urine protein, serum AST/ALT, and pathologic analysis, we confirmed the possibility that pretreatment of mice with exosomes, produced by H22 hepatic tumor cells, resulted in protection against LPS-induced tissue damage, which is caused by overactivation of the immune system and inflammation response. This therapeutic strategy will raise an interesting way to search new therapeutics in pairs of diseases with complementarities in etiology and pathology, namely, a strategy of taking advantage of the mutual complementarities between diseases.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute a family of RNA-binding proteins long recognized for their roles in pre-mRNA processing. However, accumulating evidence has established hnRNPs as central and versatile regulators of immunity. In innate immunity, some hnRNP family members recognize nucleic acids and metabolites to either promote or constrain inflammatory gene expression in a context-dependent manner. In adaptive immunity, they play essential roles in B cell activation and germinal center (GC) responses, as well as T cell activation, survival, and differentiation, primarily through the precise regulation of alternative splicing (AS). Here, we review the functions of hnRNPs (with a focus on A1, A2B1, I, K, L, M, and U) across innate and adaptive immunity, and discuss critical unresolved questions, including the often-overlooked axis of species-specific regulation.