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Background C-reactive protein (CRP) has two natural isomers: C-reactive protein pentamer (pCRP) and C-reactive protein monomer (mCRP). The levels of CRP are significantly elevated in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). mCRP not only activates the endothelial cells, platelets, leukocytes, and complements, but also has a proinflammatory structural subtype that can localize and deposit in inflammatory tissues. Thus, it regulates a variety of clinical diseases, such as ischemia/reperfusion (I/R) injury, Alzheimer’s disease, age-related macular degeneration, and cardiovascular disease. We hypothesized that plasma mCRP levels are related to cardiovascular disease in AAV. Methods In this cross-sectional study, 37 patients with AAV were assessed. Brain natriuretic peptide (BNP) and mCRP in plasma were assessed by enzyme-linked immunosorbent assay (ELISA). The acute ST-segment elevation myocardial infarction (STEMI) was diagnosed by coronary angiography, and the Gensini score calculated. Echocardiography evaluated the ejection fraction (EF%), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular mass index (LVMI). Estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine, age, and gender. Results The plasma level of mCRP in AAV was significantly higher than that in healthy volunteers (P < 0.001). Then, mCRP and CRP levels were compared with and without STEMI complications in AAV. The plasma level of mCRP was higher, but that of CRP was lower in STEMI. The plasma level of mCRP was correlated with Birmingham vasculitis activity score (BVAS), eGFR, BNP, EF%, LVEDV, LVESV, LVMI, and STEMI complications’ Gensini score in AAV; however, CRP did not correlate with BNP, EF%, LVEDV, LVESV, LVMI, and Gensini score. Conclusions The plasma level of mCRP was related to cardiovascular diseases in AAV patients.

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[Background] Sphingosine-1-phosphate (S1P) plays a significant role in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). [Methods] We collected the plasma samples from 40 patients with AAV and 10 healthy volunteers. The plasma levels of S1P were tested by enzyme-linked immunosorbent assay (ELISA). The levels of serum creatinine (Scr) were tested by rate method, and then the glomerular filtration rate (eGFR) of the patients was calculated from the Scr, age, and gender. Prothrombin time (PT), partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), fibrinogen reduction product (FDP), D-dimer and C-reactive protein (CRP) were tested by turbidimetric inhibition immunoassays. Platelets (PLT) were tested by fluorescently-labelled electrical impedance method. [Results] The plasma levels of S1P was significantly higher in AAV patients than in healthy volunteers. Correlation analysis showed that plasma levels of S1P were negatively correlated with glomerular filtration (p=0.022, r=-0.306), and positively correlated with circulating levels of Birmingham vasculitis activity score (BVAS), PLT and D-dimer, (p=0.004, r=0.443; p&lt;0.001, r=0.654; p=0.006, r=0.427). The 40 patients with AAV were classified into three groups: the thromboembolism group (with complications of cerebral infarction and myocardial infarction, n=6), cerebral ischemia group (n=4), and cerebral hemorrhage group (n=2). The plasma levels of S1P were highest in the thromboembolism group and lowest in the cerebral hemorrhage group (p=0.003). [Conclusions] Plasma levels of S1P were associated with circulating levels of D-dimer, PLT, and BVAS in the patients with AAV. Hence, plasma S1P level can be used as a biomarker to predict coagulation-related complications in AAV.

Atherosclerosis is a chronic systemic inflammatory disease that causes severe cardiovascular events. B cell lymphoma 2-associated athanogene (BAG3) was proven to participate in the regulation of tumor angiogenesis, neurodegenerative diseases, and cardiac diseases, but its role in atherosclerosis remains unclear. Here, we aim to investigate the role of BAG3 in atherosclerosis and elucidate the potential molecular mechanism. In this study, ApoE−/− mice were given a tail-vein injection of BAG3-overexpressing lentivirus and fed a 12-week high-fat diet (HFD) to investigate the role of BAG3 in atherosclerosis. The overexpression of BAG3 reduced plaque areas and improved atherosclerosis in ApoE−/− mice. Our research proves that BAG3 promotes autophagy in vitro, contributing to the suppression of EndMT in human umbilical vein endothelial cells (HUVECs). Mechanically, autophagy activation is mediated by BAG3 via the interaction between BAG3 and its chaperones HSP70 and HSPB8. In conclusion, BAG3 facilitates autophagy activation via the formation of the chaperone-assisted selective autophagy (CASA) complex interacting with HSP70 and HSPB8, leading to the inhibition of EndMT during the progression of atherosclerosis and indicating that BAG3 is a potential therapeutic target for atherosclerosis.