High-mobility group box 1 and its related receptors: potential therapeutic targets for contrast-induced acute kidney injury.

Percutaneous coronary intervention (PCI) is a crucial diagnostic and therapeutic approach for coronary heart disease. Contrast agents' exposure during PCI is associated with a risk of contrast-induced acute kidney injury (CI-AKI). CI-AKI is characterized by a sudden decline in renal function occurring as a result of exposure to intravascular contrast agents, which is associated with an increased risk of poor prognosis. The pathophysiological mechanisms underlying CI-AKI involve renal medullary hypoxia, direct cytotoxic effects, endoplasmic reticulum stress, inflammation, oxidative stress, and apoptosis. To date, there is no effective therapy for CI-AKI. High-mobility group box 1 (HMGB1), as a damage-associated molecular pattern molecule, is released extracellularly by damaged cells or activated immune cells and binds to related receptors, including toll-like receptors and receptor for advanced glycation end product. In renal injury, HMGB1 is expressed in renal tubular epithelial cells, macrophages, endothelial cells, and glomerular cells, involved in the pathogenesis of various kidney diseases by activating its receptors. Therefore, this review provides a theoretical basis for HMGB1 as a therapeutic intervention target for CI-AKI.

Vaspin Alleviates Sepsis-Induced Cardiac Injury and Cardiac Inflammation by Inhibiting Kallikrein 7 in Mice.

Background: Vaspin is an important adipokine that is involved in cardiovascular diseases. This study is aimed at investigating whether vaspin participates in sepsis-induced cardiac injury and explored the possible mechanism. Methods: First, cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) were used to establish a mouse model of sepsis, and cardiac vaspin expression was examined. In addition, after pretreatment with vaspin or phosphate-buffered saline (PBS), wild-type (WT) mice underwent CLP to establish a septic model and received sham as a control. Finally, WT mice and kallikrein 7 (KLK7-/-) mice were underwent CLP with or without vaspin pretreatment. Results: Mice that underwent CLP and were administered LPS exhibited increased vaspin expression in both the heart and serum compared with sham- or saline-treated mice. In CLP mice, pretreatment with vaspin reduced mortality and alleviated the expression of cardiac injury markers and cardiac dysfunction. In addition, vaspin reduced the cardiac levels of CD45+ cells and CD68+ cells, alleviated the cardiac inflammatory response, and reduced cardiomyocyte apoptosis. The protective effects of vaspin on CLP mice were masked by the deletion of KLK7, which was demonstrated to be a downstream signal of vaspin. Conclusions: Vaspin alleviates cardiac inflammation and plays a protective role in sepsis-induced cardiac injury by reducing KLK7 expression.