The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis.

BACKGROUND: The significance of S100A8/A9 and S100A12 in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. This study was dedicated to exploring the potential pathogenic roles of S100A8/A9 and S100A12 in patients with myeloperoxidase (MPO)-ANCA-positive vasculitis. METHODS: Serum and urine concentrations of S100A8/A9 and S100A12 of forty-two AAV patients were evaluated. The influence of S100A8/A9 and S100A12 on the chemotaxis, the apoptosis, the release of IL-1ß, the complement activation, the respiratory burst, as well as the neutrophil extracellular traps (NETs) formation of MPO-ANCA-activated neutrophils was investigated. RESULTS: The serum and urine S100A8/A9 and S100A12 of active MPO-AAV significantly increased (compared with inactive AAV and healthy controls, p < 0.001) and were correlated with the severity of the disease. In vitro study showed that S100A8/A9 and S100A12 activated the p38 MAPK/NF-κB p65 pathway, increased the chemotaxis index (CI) and the release of IL-1ß, extended the life span, and enhanced the complement activation ability of MPO-ANCA-activated neutrophils. The Blockade of TLR4 and RAGE inhibited the effects of S100A8/A9 and S100A12. All above-mentioned effects of S100A8/A9 and S100A12 were ROS-independent because neither S100A8/A9 nor S100A12 enhanced the ROS formation and NETs formation of MPO-ANCA-activated neutrophils. CONCLUSION: S100A8/A9 and S100A12 serve as markers for assessing the disease severity, and they may also play a role in MPO-AAV pathogenesis.

The Relation Between Red Blood Cell Distribution Width and Coronary Atherosclerotic Plaque Vulnerability Detected by Intracoronary Optical Coherence Tomography.

BACKGROUND: A higher red blood cell distribution width (RDW) predicts major adverse cardiac events in patients with coronary artery disease (CAD). However, there are only a few studies regarding the relationship between RDW and vulnerable plaques. Thus, the purpose of the present study is to retrospectively explore the predictive value of the association between RDW and plaque vulnerability assessed by optical coherence tomography (OCT) in patients with cardiovascular (CV) diseases. METHODS: This study included 35 patients with stable angina pectoris (SAP) and 70 patients with the acute coronary syndrome (ACS). We documented clinical features as well as peripheral RDW. Plaque vulnerability was determined by OCT. We defined thin-cap fibroatheroma (TCFA) as a lipid-rich plaque (fibrous cap <65 µm thick). RESULTS: Plaque rupture was detected more frequently in patients with ACS compared with patients with SAP (62.9 vs. 2.9%, p<0.001, and the corresponding TCFA were 50.69±15.68 vs. 80.03±21.60 µm, p<0.001, respectively). A higher RDW was found in patients with ACS than in patients with SAP (p<0.001). A cut-off value of RDW >13.85% could detect ruptured plaque with a sensitivity of 72.3% and a specificity of 62%. CONCLUSION: TCFA and plaque rupture were detected more frequently in patients with ACS compared with SAP. Elevated RDW was positively the predictive value of the association between plaque vulnerability.

Acute myocardial infarction in twin pregnancy after assisted reproduction: A case report.

BACKGROUND: Acute myocardial infarction (AMI) during pregnancy is rare, especially in twin pregnancy, and it can endanger the lives of the mother and children. Except for conventional cardiovascular risk factors, pregnancy and assisted reproduction can increase the risk of AMI during pregnancy. AMI develops secondary to different etiologies, such as coronary spasm and spontaneous coronary artery dissection. CASE SUMMARY: A 33-year-old woman, with twin pregnancy in the 31st week of gestation, presented to the hospital with intermittent chest tightness for 12 wk, aggravation for 1 wk, and chest pain for 4 h. Combined with the electrocardiogram and hypersensitive troponin results, she was diagnosed with acute ST-elevation myocardial infarction. Although the patient had no related medical history, she presented several risk factors, such as age greater than 30 years, assisted reproduction, and hyperlipidemia. After diagnosis, the patient received antiplatelet and anticoagulant treatment. Cesarean section and coronary angiography performed 7 d later showed stenosis and thrombus shadow of the right coronary artery. After receiving medication, the patient was in good condition. CONCLUSION: This case suggests that, with the widespread use of assisted reproductive technology, more attention should be paid to perinatal healthcare, especially when chest pain occurs, to facilitate early diagnosis and intervention of AMI, and the etiology of AMI in pregnancy needs to be differentiated, especially between coronary spasm and spontaneous coronary artery dissection.

Urinary mitochondrial DNA is a useful biomarker for assessing kidney injury of antineutrophil cytoplasmic antibody -associated vasculitis.

BACKGROUND: The value of urinary mitochondrial DNA (mtDNA) for assessing kidney injury of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) was investigated. METHODS: Thirty-nine kidney biopsy-proved myeloperoxidase (MPO)-ANCA associated AAV patients were enrolled and analyzed. RESULTS: The average urinary mtDNA of patients was significantly higher than that of normal controls (3372.74 ± 1859.72 vs. 474.90 ± 123.59 copy/nmol creatinine, p < 0.001). The patients who needed dialysis at disease onset had the highest levels of urinary mtDNA (5072.23 ± 1302.87 copy/nmol creatinine). Urinary mtDNA positively correlated with urinary neutrophil gelatinase-associated lipocalin (R = 0.661, P < 0.001) and negatively correlated with estimated glomerular filtration rate (R = -0.515, P = 0.001). The urinary mtDNA level of crescentic class (4703.08 ± 1744.31 copy/nmol creatinine) was higher than that of mixed class (3258.14 ± 1158.99 copy/nmol creatinine) and focal class (2268.15 ± 1897.63 copy/nmol creatinine). Univariate correlation analysis showed urinary mtDNA positively correlated with interstitial neutrophils (R = 0.471, P = 0.048) and glomerular neutrophils (R = 0.673, P = 0.002) in kidney biopsy. Among 13 patients who needed hemodialysis at disease onset, 10 patients who got renal recovery had higher urinary mtDNA than 3 patients who remained dialysis dependent (5455.20 ± 1174.64 vs. 3795.67 ± 893.34 copy/nmol creatinine, p = 0.047). CONCLUSIONS: Urinary mtDNA increases in AAV with kidney injury, and its levels correlate with the severity of kidney injury and neutrophils infiltration in pathology.

Pathological severity determines the renal recovery for anti-myeloperoxidase antibody-associated vasculitis requiring dialysis at disease onset: a retrospective study.

BACKGROUND: Many patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) need dialysis at disease onset due to severe kidney injury. Determining whether they can become dialysis independent is an important clinical assessment. METHODS: Forty kidney biopsy-proved myeloperoxidase (MPO)-ANCA associated AAV patients who required dialysis at disease onset were enrolled. Relationships between laboratory and pathological characteristics and prognoses were analyzed. RESULTS: Twenty-five patients obtained dialysis independence within 3 months, while the other 15 patients remained dialysis dependent. No sclerotic class was identified among the 40 patients. Only two biopsies exhibited focal class diagnoses and both these patients recovered their renal function. The renal recovery rate of the 20 patients with mixed class was significantly lower than that of the 18 patients with crescentic class (40.0% vs. 83.3%, p = 0.006). Receiver operating characteristics (ROC) curves showed fibrous crescent+global glomerulosclerosis greater than 32.6% was a strong predictor of dialysis dependence with a sensitivity of 93.3% and specificity of 88.0%. When the percentage of fibrous crescent+global glomerulosclerosis exceeded 47.9%, dialysis independence was not possible. Correlation analysis indicated that platelet counts were negatively correlated with the percentage of fibrous crescent+global glomerulosclerosis (R = -0.448, p = 0.004). Most patients with increased platelets (84.62%) obtained renal recovery. Compared with methylprednisolone pulse therapy, plasma exchange accelerated renal recovery (29.4 ± 15.6 vs. 41.4 ± 11.7 days, p = 0.039). CONCLUSIONS: For MPO-ANCA AAV who required dialysis at disease onset, crescentic and mixed classes accounted for the majority of patients in our cohort. The renal outcome of mixed class patients was worse than that of crescentic class. A high proportion of fibrous crescent+global glomerulosclerosis is a predictor of dialysis dependence. Increased platelet count is associated with active and reversible renal lesions.

Obstructive sleep apnea is associated with severity and long-term prognosis of acute coronary syndrome.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disease in patients with acute coronary syndrome (ACS) and associated with an increased risk of fatal and nonfatal cardiovascular events. However, most patients in previous study were treated with bare metal stents and the sample sizes were relatively low. The goal of this study was to evaluate the influence of OSA on the severity and prognosis of patients admitted for ACS. METHODS: In this prospective cohort study, we enrolled patients with ACS who were hospitalized for coronary angiogram/percutaneous coronary intervention and undergone polysomnography. We divided the patients into two groups: moderate to severe OSA group [apnea-hypopnea index (AHI) > 15 events/h] and control group (AHI ≤ 15 events/h). They were followed up for up 32 months. Then, we compared the ACS severity and long-term major adverse cardiovascular events (MACE) in patients with different severity of OSA. RESULTS: Five hundred and twenty nine patients were included in the final analysis, with 76% of them being men and an average age of 59 ± 10 years. The overall mean AHI is 29 ± 19 events/h, 70.5% of them (373/529) being with moderate to severe OSA and 29.5% (156/529) assign into control group. Compared with controls, patients with moderate or severe OSA exhibited a higher prevalence of hypertension as well as higher body mass index, SYNTAX score, Epworth score and length of hospitalization. With a median follow-up duration of 30 months, accumulative rate of MACE was also higher in patients with moderate or severe OSA than that in the control group (8.6% vs. 3.2%, P = 0.028). After adjusting for baseline confounders by cox regression model, moderate to severe OSA was an independent risk factor of long-term MACE (P = 0.047, HR = 1.618, 95% CI: 1.069-3.869). CONCLUSIONS: The results of this study demonstrate that moderate or severe OSA is correlated with disease severity and associated with worse long-term prognosis in ACS patients. The results raising the possibility that early diagnose and interventions of OSA could improve long-term outcomes in ACS patients.

Valsartan Protects Against Contrast-Induced Acute Kidney Injury in Rats by Inhibiting Endoplasmic Reticulum Stress-Induced Apoptosis.

BACKGROUND AND OBJECTIVE: Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the administration of iodinated contrast media (CM) for diagnostic and interventional cardiovascular procedures and is associated with substantial morbidity and mortality. While the preventative measures can mitigate the risk of CI-AKI, there remains a need for novel and effective therapeutic approaches. The pathogenesis of CI-AKI is complex and not completely understood. CM-induced renal tubular cell apoptosis caused by the activation of endoplasmic reticulum (ER) stress is involved in CIAKI. We previously demonstrated that valsartan alleviated CM-induced human renal tubular cell apoptosis by inhibiting ER stress in vitro. However, the nephroprotective effect of valsartan on CI-AKI in vivo has not been investigated. Therefore, the aim of this study was to explore the protective effect of valsartan in a rat model of CI-AKI by measuring the amelioration of renal damage and the changes in ER stressrelated biomarkers. METHOD AND RESULTS: Our results showed that the radiocontrast agent meglumine diatrizoate caused significant renal insufficiency, renin-angiotensin system (RAS) activation, and renal tubular apoptosis by triggering ER stress through activation of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), caspase 12, CCAAT/enhancer-binding protein-homologous protein (CHOP) and c-Jun N-terminal protein kinase (JNK) (P<0.05; n=6 in each group). Pre-treatment with valsartan significantly alleviated renal dysfunction, pathological injury, and apoptosis along with the inhibition of ER stressrelated biomarkers (P<0.05; n=8 in each group). CONCLUSION: Valsartan could protect against meglumine diatrizoate-induced kidney injury in rats by inhibiting the ER stress-induced apoptosis, making it a promising strategy for preventing CI-AKI.