Elevated plasma levels of osteoglycin in cardiovascular patients: a systematic review and meta-analysis.

BACKGROUND: To evaluate the levels of osteoglycin (OGN) in patients with cardiovascular disease. METHODS: A meta-analysis was conducted on retrospective studies that compared patients with and without cardiovascular disease. Data including the levels of OGN, low density lipoprotein (LDL), and high density lipoprotein (HDL) were analyzed and expressed as mean differences (MD) with a 95% confidence interval (CI). RESULTS: This meta-analysis included 6 studies with a total of 1,443 patients. The results showed that the concentration of OGN in the blood of patients with cardiovascular disease was significantly elevated compared to that observed in control patients. There were no significant differences in LDL and HDL expression between cardiovascular patients and control patients. Sensitivity analysis and funnel plots showed that this investigation was robust and had low publication bias. DISCUSSION: This report demonstrated that the blood concentration of OGN in patients with cardiovascular disease is significantly elevated compared to that in control patients. Furthermore, the elevated levels of OGN suggests that OGN may be a biomarker/or therapeutic target for patients with cardiovascular disease. Although the structure of OGN is simple, it is indispensable in many important life processes. It plays a protective role in the occurrence of cardiovascular and cerebrovascular diseases through antioxidant, anti-inflammatory, anti-apoptosis and increasing tolerance to hypoxia.

Growth differentiation factor-15 combined with N-terminal prohormone of brain natriuretic peptide increase 1-year prognosis prediction value for patients with acute heart failure: a prospective cohort study.

BACKGROUND: Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers. The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15 (GDF-15) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in assessing hospitalized patients with acute heart failure (AHF). METHODS: In total, 260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016. Medical history and blood samples were collected within 24 h after the admission. The primary endpoint was the all-cause mortality within 1 year. The patients were divided into survival group and death group based on the endpoint. With established mortality risk factors and serum GDF-15 level, receiver-operator characteristic (ROC) analyses were performed. Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15. RESULTS: Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors (P < 0.001). In ROC analyses, area under curve (AUC) for GDF-15 to predict 1-year mortality was 0.707 (95% confidence interval [CI]: 0.648-0.762, P < 0.001), and for NT-proBNP was 0.682 (95% CI: 0.622-0.738, P < 0.001). No statistically significant difference was found between the two markers (P = 0.650). Based on the optimal cut-offs (GDF-15: 4526.0 ng/L; NT-proBNP: 1978.0 ng/L), the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction (AUC = 0.743, 95% CI: 0.685-0.795, P < 0.001). CONCLUSIONS: GDF-15, as a prognostic marker in patients with AHF, is not inferior to NT-proBNP. Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis. CLINICAL TRIAL REGISTRATION: ChiCTR-ONC-12001944, http://www.chictr.org.cn.

Traditional Chinese medicine Qiliqiangxin attenuates phenylephrine-induced cardiac hypertrophy via upregulating PPARγ and PGC-1α.

BACKGROUND: Clinical study has demonstrated that the traditional Chinese medicine Qiliqiangxin (QLQX) has protective effects on heart failure. Phenylephrine (PE) is an important inducing factor for cardiac hypertrophy and our previous studies have showed that QLQX attenuates PE-induced cardiac hypertrophy. Besides, QLQX protects against cardiac remodeling after myocardial infarction via activating PPARγ. However, whether QLQX prevents PE-induced cardiac hypertrophy through PPARγ and its coactivator PGC-1α is still unknown. METHODS: The effects of QLQX were investigated based on PE induced cardiac hypertrophy mouse models. Echocardiography and hematoxylin-eosin (HE) staining were used to determine cardiac function and cross-sectional area, respectively. Quantitative real time PCR (qRT-PCR) was used to determine ANP and BNP expressions. Based on primary neonatal rat ventricular cardiomyocytes (NRVMs) treated with PE, the cell size and expressions of ANP and BNP were determined by immunofluorescent staining and qRT-PCR, respectively. In addition, western blot was used to determine PPARγ and PGC-1α expressions. RESULTS: In present study, we confirmed that QLQX could significantly attenuate cardiac hypertrophy in mice treated with PE. Then we showed that PPARγ and PGC-1α were downregulated in PE-induced cardiac hypertrophy, and QLQX could block the decrease of PPARγ and PGC-1α both in vitro and in vivo. Importantly, we found that PPARγ inhibitors or PGC-1α siRNAs eliminated the protective effects of QLQX on PE-induced cardiac hypertrophy. CONCLUSIONS: Our study suggested that QLQX prevents from PE-induced cardiac hypertrophy by activating PPARγ and its coactivator PGC-1α.

Brachial-ankle pulse wave velocity compared with mean arterial pressure and pulse pressure in risk stratification in a Chinese population.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) can be easily measured in an observer-independent way, but lacks robust population-based validation in terms of fatal combined with nonfatal outcomes. METHOD: To address this issue, we studied 4251 Chinese randomly recruited Gaoyou County (54.1% women; mean age, 52.1). RESULTS: In the whole study population, mean values were 102.4 mmHg for mean arterial pressure (MAP), 51.1 mmHg for pulse pressure, and 14.8 m/s for baPWV. Over 4.4 years (median), 74 participants experienced a fatal or nonfatal cardiovascular event and 44 a stroke. In multivariable-adjusted Cox regression, standardized hazard ratios expressing the risk of a composite cardiovascular endpoint were 1.77 (95% confidence interval, 1.43-2.20), 1.37 (1.14-1.64) and 1.50 (1.26-1.78) for MAP, PP and baPWV, respectively; the corresponding hazard ratios for stroke were 1.82 (1.39-2.38), 1.39 (1.12-1.74) and 1.53 (1.25-1.89). baPWV did not add to the prediction of cardiovascular events or stroke by MAP (hazard ratios for baPWV, 1.25 and 1.27, respectively; P ≥ 0.053) but refined models including PP (hazard ratios, 1.42 and 1.45; P ≤ 0.0033). The optimized baPWV threshold, obtained by maximizing Youden's index (16.7 m/s), increased the integrated discrimination improvement over and beyond MAP (+1.27%; P = 0.021) and PP (+1.37%; P = 0.038) for the cardiovascular outcome, but not stroke, and increased the net reclassification improvement for both endpoints (≥42.2%; P ≤ 0.004). CONCLUSION: With fatal and nonfatal cardiovascular and cerebrovascular endpoints as outcome, baPWV marginally increases risk stratification over and beyond MAP, but is a better predictor than PP. A threshold of 16.7 m/s might be used in Chinese populations.

Hypertension related knowledge and behaviour associated with awareness, treatment and control of hypertension in a rural hypertensive population: a community based, cross-sectional survey.

BACKGROUND AND OBJECTIVE: Hypertension-related knowledge and behaviour have been identified as influential factors associated with awareness, treatment and control of hypertension in urban regions. However, there were few studies on rural areas. This study aims to investigate whether hypertension related knowledge and behaviour were associated with hypertension awareness, treatment and control in Gaoyou, a rural area of Jiangsu province, China. METHODS: A cross-sectional, population-based survey was conducted among hypertensive individuals in rural areas of Gaoyou, the south-eastern of China in 2010. We identified 1943 subjects with hypertension among 4536 subjects participated in this study and collected information about medical history, use of medication, hypertension related knowledge and behaviour by a standardized questionnaire. RESULTS: This study showed that 41.07% of subjects were aware of their disease, 30.01% of subjects were taking antihypertensive medication and 5.04% of subjects controlled their blood pressure. Multivariate logistic regression analysis showed that subjects who knew the threshold, the lifelong treatment of hypertension and measured blood pressure at least once a year had better detection, treatment or control of hypertension. CONCLUSION: Hypertension related knowledge and behaviour were associated with awareness, treatment and control rate of hypertension in the rural areas of south-eastern China.

Quality control of the blood pressure phenotype in the Gaoyou population study.

The Korotkoff approach is the only blood pressure (BP) measurement technique that allows contemporary data to be compared with decades of research. We randomly recruited 4483 people (53.3% women; mean age 52.1 years) from Gaoyou County, Jiangsu Province, China. Nine observers recorded the participants™ BP three times consecutively following Chinese Society of Hypertension guidelines. We assessed the BP phenotype based on five criteria: completeness of readings, percentage of identical BP readings, odd BP readings, end-digit preference and trends in BP from the first to the third reading. The proportion of participants with identical readings were 2.0% and 3.1% for systolic (SBP) and diastolic blood pressure (DBP), respectively. Among 26,898 BP values, 0.3% ended in an odd number. Among observers, the prevalence of identical readings varied from 0% to 5.3% for SBP and from 0% to 6.8% for DBP. Compared with the expected frequency of 20%, those ending in 0 had a lower frequency (17.2%; p < 0.001), whereas those ending in 8 had a higher frequency (22.4%; p < 0.001). From the first to the third measurement, SBP and DBP decreased (p < 0.001) by 0.87 and 0.55 mmHg, respectively. In conclusion, the procedures set up in the Gaoyou study produced a high-quality BP phenotype.

Association of CYBA rs7195830 polymorphism with estimated glomerular filtration rate in an adult Han sample from Jiangsu province, China.

BACKGROUND: Reactive oxygen species are thought to contribute to the development of renal damage. The P22phox subunit of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase, encoded by the cytochrome b245a polypeptide gene, CYBA, plays a key role in superoxide anion production. We investigated the association of CYBA rs7195830 polymorphism with estimated glomerular filtration rate (eGFR) and the role it plays in the pathogenesis of chronic kidney disease (CKD) in a Han Chinese sample. METHODS: The Gaoyou study enrolled 4473 participants. Serum levels of creatinine were measured and eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equations. The CYBA polymorphisms were genotyped. Then we investigated the association between eGFR and the rs7195830 polymorphism in the recessive model. RESULTS: The AA genotype of rs7195830 was associated with significantly lower values of eGFR compared with the GG and AG genotypes ((102.76 ± 17.07) ml×min(-1)×1.73 m(-2) vs. (105.08 ± 16.30) ml×min(-1)± 1.73 m(-2)). The association remained significant in the recessive model after adjusting for age, gender, body mass index, smoking, hypertension, diabetes mellitus, uric acid, triglyceride, low density lipoprotein cholesterol and high density lipoprotein cholesterol (ß=1.666, P=0.031). The rs7195832 AA genotype was an independent risk factor for CKD: eGFR <60 ml×min(-1)×1.73 m(-2) (odds ratio=3.32; 95% CI=1.21-9.13). CONCLUSION: The AA genotype of rs7195830 is independently associated with lower estimated glomerular filtration rate and is significantly associated with CKD.

Increased stromal-cell-derived factor 1 enhances the homing of bone marrow derived mesenchymal stem cells in dilated cardiomyopathy in rats.

BACKGROUND: Stem cell transplantation has been shown to have beneficial effects on dilated cardiomyopathy. However, mechanism for stem cell homing to cardiac tissue in dilated cardiomyopathy has not yet been elucidated. METHODS: Mesenchymal stem cells were obtained from rat bone marrow, expanded in vitro, and labeled with (99m)Tc. Cardiomyopathy model was induced by doxorubicin in rats. (99m)Tc labeled cells were infused into the left ventricles in cardiomyopathy and control rats. Sixteen hours after injection, animals were sacrificed and different tissues were harvested to measure specific radioactivity. By use of real-time polymerase chain reaction and immunohistochemistry, mRNA and protein expressions for stromal-cell-derived factor 1 in cardiac tissue were measured. RESULTS: Labeling efficiency of mesenchymal stem cells was (70.0 ± 11.2)%. Sixteen hours after mesenchymal stem cell transplantation, the heart-to-muscle radioactivity ratio was increased significantly in cardiomyopathy hearts as compared to control hearts. Both mRNA and protein expressions of stromal-cell-derived factor 1 were up-regulated in cardiomyopathy hearts as compared with control hearts. CONCLUSION: In dilated cardiomyopathy induced by doxorubicin up-regulated expression of stromal-cell-derived factor 1 in heart may induce mesenchymal stem cells home to the heart.

[Relationship between high-sensitive c-reactive and blood pressure].

OBJECTIVE: To investigate the relationship between c-reactive protein (CRP) and blood pressure in a general population. METHODS: We randomly selected 3889 subjects aged 18 - 74 years stratified by gender and age in Baqiao, a rural area of Jiangsu Province. A standardized questionnaire was used to collect information on medical history, smoking, alcohol intake and use of medications. Blood pressure was measured by mercury sphygmomanometer. Serum CRP (hCRP) concentration was measured using a high sensitivity BNprosec immunonephelometric assay. Subjects were divided into 4 groups according to their interquartile range of CRP levers: group Q1 (men hCRP < 2.04 mg/L; women hCRP < 1.80 mg/L); group Q2 (men 2.04 mg/L ≤ hCRP < 3.01 mg/L; women 1.80 mg/L ≤ hCRP < 2.76 mg/L); group Q3 (men 3.01 mg/L ≤ hCRP < 4.14 mg/L; women 2.76 mg/L ≤ hCRP < 3.84 mg/L); and group Q4 (men 4.14 mg/L ≤ hCRP; women 3.84 mg/L ≤ hCRP). RESULTS: Systolic blood pressure (SBP, adjusted P = 0.016) and pulse pressure (PP, adjusted P = 0.003) of men and PP (adjusted P = 0.002) of women were increased in proportion to increased CRP levels. Diastolic blood pressure was not associated with CRP levels. Multiple stepwise regression analysis showed that logCRP was independently associated with SBP and PP in men and PP in women. hCRP was independently associated with hypertension in men. Compared with group Q1, male people in group Q4 faced a 40.4% (95% confidence interval: 4.9% - 87.9%) higher risk of hypertension. CONCLUSIONS: hCRP was independently associated with PP in men and women, and SBP in men. hCRP was independently associated with hypertension in men but not in women in this study population.

Structural basis for ubiquitin recognition by a novel domain from human phospholipase A2-activating protein.

Ubiquitin (Ub) is an essential modifier conserved in all eukaryotes from yeast to human. Phospholipase A(2)-activating protein (PLAA), a mammalian homolog of yeast DOA1/UFD3, has been proposed to be able to bind with Ub, which plays important roles in endoplasmic reticulum-associated degradation, vesicle formation, and DNA damage response. We have identified a core domain from the PLAA family ubiquitin-binding region of human PLAA (residues 386-465, namely PFUC) that can bind Ub and elucidated its solution structure and Ub-binding mode by NMR approaches. The PFUC domain possesses equal population of two conformers in solution by cis/trans-isomerization, whereas the two isomers exhibit almost equivalent Ub binding abilities. This domain structure takes a novel fold consisting of four beta-strands and two alpha-helices, and the Ub-binding site on PFUC locates in the surface of alpha2-helix, which is to some extent analogous to those of UBA, CUE, and UIM domains. This study provides structural basis and biochemical information for Ub recognition of the novel PFU domain from a PLAA family protein that may connect ubiquitination and degradation in endoplasmic reticulum-associated degradation.

Decreased small arterial compliance with increased serum vascular endothelial growth factor-A and circulating endothelial progenitor cell in dilated cardiomyopathy.

BACKGROUND: Evidence showed that both myocardium and blood vessels were damaged in dilated cardiomyopathy (DCM). However, the changes in arterial compliance, serum cytokines and circulating endothelial progenitor cells (EPC), and their correlations remain unknown. METHODS: Sixty-five DCM patients and 49 healthy volunteers were studied. Both large artery compliance (C(1)) and small artery compliance (C(2)) were measured with the CVProfilor DO-2020. Quantitative enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of vascular endothelial growth factor-A (VEGF-A) and VEGF receptor 2 (VEGF-R(2)). Circulating EPC was assessed by EPC colony-forming assays and flow cytometry (CD133(+)/CD34(+) cells). Phagocytized DiI-acLDL and binded FITC-UEA-I were used to analyze endothelial lineage marker expression by immunofluorescence. RESULTS: Although C(2) was markedly lower in DCM patients than in control group ((3.8+/-1.8) ml/mmHg x 100 vs (5.0+/-2.2) ml/mmHg x 100, P<0.0001), there was no statistically significant difference in C(1) between the two groups (P>0.05). Levels of VEGF-A, the numbers of colony-forming units (CFU) and the fractions of EPC were obviously higher in DCM patients than in control group ((127.6+/-139.5) pg/ml vs (58.8+/-42.9) pg/ml, P<0.0001; (2.5+/-1.5)% vs (0.5+/-0.3)%, P < 0.05; 23.5+/-12.8 vs 10.8+/-7.4, P<0.01, respectively) and however, there was no significant difference in VEGF-R(2) between two groups (P>0.05). LgVEGF-A was positively correlated with the number of EPC-CFU (r=0.435; P<0.05) and inversely correlated with C(2) (r= -0.543; P<0.001) in DCM patients. CONCLUSIONS: The reduction of C(2), a sensitive marker reflecting endothelial dysfunction, was observed in DCM patients and closely related to the increase in serum VEGF-A.