Serum lysosomal-associated membrane protein-2 levels are increased in small and medium-vessel vasculitis, especially in polyarteritis nodosa.

OBJECTIVES: Lysosomal-associated membrane protein-2 (LAMP-2) is a highly glycosylated type I glycoprotein ex- pressed on the membranes of neutrophils, endothelial cells and other cells, which are closely linked to subsets of systematic vasculitis. The aim of this study was to investigate whether serum LAMP-2 can be used as a biomarker in small and medium vessel vasculitis (SMVV). METHODS: Serum samples from 39 patients with SMVV (including ANCA-associated vasculitis (AAV) and polyarteritis nodosa (PAN)) confirmed by angiography and/or biopsy and 78 healthy controls (HC) were collected. Serum LAMP-2 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum LAMP-2 levels in SMVV patients were increased compared with HC (p<0.001). Serum LAMP-2 levels were significantly different between patients with active stage and those with inactive stage (p=0.024). Patients with renal involvement had higher LAMP-2 levels than patients with non-renal involvement at presentation (p=0.022). Furthermore, serum LAMP-2 levels were correlated with Birmingham Vasculitis Activity Score (BVAS), C-reactive protein (CRP), hypersensitive CRP (Hs-CRP), serum creatinine (Scr) and 24-hour proteinuria (all p<0.05). Among SMVV subsets, serum LAMP-2 levels were signi cantly higher in PAN compared with AAV (p=0.003). In PAN patients, serum LAMP-2 levels were correlated with BVAS and Hs-CRP (all p<0.05). CONCLUSIONS: Serum LAMP-2 levels can reflect the disease activity and renal involvement of SMVV. Furthermore, serum LAMP-2 levels were significantly higher in PAN compared with AAV, and associated with disease activity. LAMP-2 might be a potential biomarker for SMVV, especially in PAN.

Association Between Polymorphisms of ADRBK1 Gene and Plasma Renin Activity in Hypertensive Patients: A Case-Control Study.

BACKGROUND Renin is the first step of the RAS cascade, which is a major regulator of salt-volume homeostasis. Adrenergic beta receptor kinase 1 (ADRBK1) plays important roles in regulating blood pressure via the epithelial Na+ channel (ENaC), which plays an important role in Na+ reabsorption in the renal collecting duct. The present case-control study was designed to investigate the potential relationship between polymorphisms of ADRBK1 and plasma renin activity (PRA) in hypertension. MATERIAL AND METHODS We recruited 1831 hypertensive and 422 normotensive Han Chinese subjects. Sitting PRA (ng/mL/h) was measured using radioimmunoassay method. Hypertensive patients were classified into 4 renin categories via PRA quartile. Single-nucleotide polymorphisms (SNPs) of the ADRBK1 gene (rs1894111, rs4930416, rs7127431, rs12286664, and rs3730147) were identified via TaqMan polymerase chain reaction. RESULTS Comparison of the hypertensive group and the control group showed significant differences in distribution of genotypes and alleles of rs1894111 (P<0.05). Moreover, distribution of the dominant model (CC vs. CT+TT) in rs1894111 was lower in the hypertensive group than in the control group (P<0.05). Subjects were classified into 4 subgroups based on PRA quartile; the dominant model (CC vs. CT+TT) of rs1894111 was significantly lower in the quartile 1 group (the group with the lowest PRA) than in the control group (P<0.05). Logistic regression analysis demonstrated that the dominant model (CC vs. CT+TT) of rs1894111 was significantly different in the hypertensive group (OR=1.590, 95%CI=1.022-2.474, P<0.05), particularly in the quartile 1 group (OR=1.845, 95%CI=1.119-3.042, P<0.05), but not in the quartile 4 group. CONCLUSIONS The dominant model (CC vs. CT+TT) of rs1894111 polymorphism in the ADRBK1 gene might be associated with low-renin hypertension in Han Chinese.

Relationship between surfactant proteins B and C and obstructive sleep apnea: is serum SP-B concentration a potential biomarker of obstructive sleep apnea?

BACKGROUND: Surfactant proteins B and C are mainly synthesized, secreted by alveolar type II cells, and affected by hypoxia and mechanical stretches. We hypothesized that their serum levels might be altered by intermittent hypoxia and swing of intrathoracic pressure of obstructive sleep apnea (OSA). METHODS: Consecutive 140 middle-aged males, suspicious of OSA determined by polysomnography, were studied. Surfactant proteins B and C were determined by ELISA. RESULTS: Surfactant protein B (41.39 ± 6.01 vs 44.73 ± 7.62 ng/L, p = 0.005), not C (32.60 ± 6.00 vs 32.43 ± 6.44 ng/L, p = 0.61), significantly lowered in moderate to severe OSA subjects than in non to mild OSA subjects. Severity of OSA is inversely correlated with serum surfactant protein B. Adjusting age, body mass index, and smoking history, compared to subjects with surfactant protein B (SP-B) ≥43.35 ng/L, those with SP-B <43.35 ng/L showed significantly increased 1.528-fold risk for moderate to severe OSA (p = 0.009), whereas no association between surfactant protein C and OSA was observed. Prevalence of moderate to severe OSA in lower SP-B group is higher than that in higher SP-B group (62.7 vs 38.4 %, p = 0.003). Serial and parallel tests on Epworth sleep scale (ESS) and SP-B evaluation can be complementary and prove helpful with high specificity (94.44 %) and sensitivity (84.48 %) to detect moderate to severe OSA. CONCLUSIONS: Serum surfactant protein B, rather than C, is decreased in some individuals with moderate to severe OSA, compared to non to mild OSA subjects. Serum surfactant protein B might be a potential biomarker to diagnose OSA.

Anti-atherosclerotic effect of traditional fermented cheese whey in atherosclerotic rabbits and identification of probiotics.

BACKGROUND: Traditional fermented cheese whey (TFCW), containing probiotics, has been used both as a dairy food with ethnic flavor and a medicine for cardiovascular disease, especially regulating blood lipid among Kazakh. We therefore investigated anti-atherosclerotic effects of TFCW in atherosclerotic rabbits and identified lactic acid bacteria (LAB) and yeasts in TFCW. METHODS: Atherosclerotic rabbits were induced by administration of atherosclerotic diet for 12 weeks and divided randomly into three groups and treated for 4 weeks with Simvastatin (20 mg/kg) or TFCW (25 mg/kg) and (50 mg/kg). In addition, a normal control group and an atherosclerotic group were used for comparison. All drugs were intragastrical administered once daily 10 mL/kg for 4 weeks. Body weight (BW), lipid profiles, C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were tested and theromatous plaques and the number of foam cells and infiltrating fibroblast cells in the thoracic aorta endothelium was evaluated by hematoxylin and eosin stainin. LAB and yeasts were isolated and purified by conventional techniques and identified using morphological and biochemical properties as well as gene sequences analysis. RESULTS: After 4 weeks of treatment, high and low dose TFCW decreased serum TC, TG, LDLC, CRP, VCAM-1 and ICAM-1 (P < 0.05) compared to atherosclerotic group, and increased HDL-C (P < 0.05) compared to normal controls. Histological analysis showed TFCW reduced VCAM-1 expression and formation of atheromatous plaques on the aortic endothelium of atherosclerotic rabbits. CONCLUSION: Seven classes of LBA from two different genera including Lactobacillus brevis, Lactobacillus kefianofaciens, Lactobacillus helveticus, Lactobacillus Casei, Lactobacillus plantarum, Lactobacillus kefiri and Lactococcus lactic as well as 2 classes of yeasts from two different genera including Saccharomyces unisporus and Issatchenkia orientalis were isolated and identified from TFCW. In summary, TFCW, containing 7 classes of LBA and 2 classes of yeasts, has significant anti-atherosclerotic potential in atherosclerotic rabbits and may modulate lipid metabolism and protect aorta in the atherosclerotic condition, which might be related to various probiotics acting through reducing the CRP, VCAM-1 and ICAM-1 levels and protecting the aortic endothelium.

Diurnal cortisol features with cardiovascular disease in hypertensive patients: a cohort study.

Objective: The hypothalamic-pituitary-adrenal (HPA) axis may be associated with cardiovascular disease (CVD) and the effects of diurnal cortisol features on future CVD remain unclear among patients with hypertension. This study aimed to evaluate the association between diurnal cortisol features and CVD in patients with hypertension. Design and methods: Participants with cortisol rhythm test at baseline in Urumqi Research on Sleep Apnea and Hypertension (UROSAH) in 2011-2013 were enrolled and followed up till 2021. Incident events included coronary heart disease, stroke, and heart failure. Cox proportional hazards model was used to evaluate the relationship between diurnal cortisol features and incident CVD. Sex-specific and sensitivity analyses were also performed. Results: In total, 2305 hypertensive participants comprised the current analytical sample. During a median follow-up of 7.2 years and 16374.9 person-years, there were 242 incident CVD cases. Multivariable Cox regression showed that steep diurnal cortisol slope (DCS) was significantly associated with decreased CVD risk (per s.d., hazard ratio (HR) = 0.86, 95% CI: 0.77-0.96, P = 0.011). Midnight cortisol was positively associated with an increased CVD risk (per s.d., HR = 1.24, 95% CI: 1.08-1.42, P = 0.002). Comparable results were observed in the sensitivity analyses. Neither midnight cortisol nor DCS was associated with incident CVD in the female subgroup. Conclusions: Flatter DCS and higher midnight cortisol levels are associated with an increased risk of CVD in patients with hypertension, especially in men. The detection of diurnal cortisol rhythm may help identify patients with hypertension at high risk of CVD.

Association of serum high mobility group box 1 levels with disease activity and renal involvement in patients with systemic vasculitis.

High mobility group box 1 (HMGB1) is a kind of proinflammatory mediator that acts as an alarmin when released by dying, injured or activated cells. Previous studies have reported that HMGB1 are closely linked to antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The present study aimed to evaluate whether serum HMGB1 levels were associated with systemic vasculitis (VAs).The study population consisted of 51 patients with VAs, 46 patients with essential hypertension (EH) and 46 healthy controls (HC). Thirty-five patients with VAs had in active stage and 16 patients with VAs in an inactive stage. Furthermore, 31 patients with VAs had renal involvement, the other 20 patients were selected for without renal involvement. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. Associations between serum HMGB1 levels with clinical and laboratory parameters were analyzed.Serum HMGB1 levels in patients with VAs were significantly higher than in EH and HC (all P < .05), and no difference regarding serum HMGB1 levels could be found between EH and HC (P = .208). Serum HMGB1 levels in VAs patients with active stage were significantly higher than those in HC and VAs patients with inactive stage (all P < .05). Patients with renal involvement and non-renal involvement had increased HMGB1 levels compared with HC (all P < .05). In addition, serum HMGB1 levels were significantly higher in patients with renal involvement compared with non-renal involvement patients (P = .001). Correlation analysis showed that serum HMGB1 levels were positive significant correlated with the Birmingham Vasculitis Activity Score, hypersensitive C reactive protein (Hs-CRP), serum creatinine (Scr) and 24-hour proteinuria (all P < .05). Among the subsets of VAs, serum HMGB1 levels were significantly higher in AAV, polyarteritis nodosa (PAN) and takayasu arteritis (TA) than in HC (all P < .05). More interestingly, serum HMGB1 were significantly higher in patients with PAN compared with AAV and TA patients (all P < .05). Furthermore, there was positive correlation between serum HMGB1 levels and Hs-CRP, Scr, and 24-hour proteinuria in patients with PAN (all P < .05).Serum HMGB1 levels are increased in patients with VAs compared with HC and EH and can reflect the disease activity and renal involvement.