The associations between plasma catestatin and coronary collateral development by multiple linear regression.

<p>The associations between plasma catestatin and coronary collateral development by multiple linear regression.</p

The differences in clinical characteristics and plasma catestatin levels between normal group and CTO group.

<p>The differences in clinical characteristics and plasma catestatin levels between normal group and CTO group.</p

The differences between good collateral group and poor collateral group among CTO patients.

<p>The differences between good collateral group and poor collateral group among CTO patients.</p

The relationship between plasma catestatin levels and Rentrop scores.

<p>The catestatin levels in the different Rentrop score groups were respectively 1.47±1.29 ng/ml (grade0, n = 12); 1.83±0.82 ng/ml (grade1, n = 8); 2.31±0.77 ng/ml (grade2, n = 14); and 2.54±0.61 ng/ml (grade3, n = 4). The differences was significant between grade0 group and grade2 group (p = 0.034).</p

The flowchart of the study subjects.

<p>The 640 patients with chest pain for suspicious CAD who underwent coronary angiography or percutaneous coronary intervention (PCI) were screened in series. According to the results of angiography, 518 patients had coronary stenosis (not CTO), 41 patients had normal coronary angigraphy, 81 patients had coronary total occlusion lesions. There were 3 patients with normal coronary angiography and 43 patients with coronary total occlusion were excluded. Finally, there were 38 patients in normal group and 38 patients in CTO group, respectively.</p

Mitochondrial Proteomic Analysis of Cisplatin Resistance in Ovarian Cancer

Epithelial ovarian cancer (EOC) is the leading cause of death among women with gynecologic malignancies and accounts for approximately 6% of cancer deaths among women. Cisplatin and its analogues form the backbone of the most active chemotherapy regimens in advanced EOC; however, development of platinum resistance is common and typically marks a transition in which curing the patient is no longer possible. An emerging theme in many cancers is that mitochondrial dysfunction contributes to an aggressive carcinogenic phenotype. We hypothesized that changes in the mitochondrial proteome are required to support development of cisplatin resistance in human EOC. To investigate this hypothesis, an organellar proteomics approach was utilized to quantify alterations in protein abundance in mitochondria enriched from isogenic cisplatin-sensitive (A2780) and -resistant (A2780-CP20) human EOC cells. Protein isolates from mitochondria-enriched fractions were analyzed by high resolution liquid chromatography–tandem mass spectrometry (LC–MS/MS), and relative abundance of identified proteins was quantified by spectral counting. Pathway analyses revealed significant increases in notch signaling pathways, cell survival, and alternate apoptotic pathways in the A2780-CP20 subtype. Among the alterations identified in the mitochondrial proteomic composition in cisplatin-resistant EOC cells, activated leukocyte cell adhesion molecule (AKAP12) and A kinase anchoring protein 12 (AKAP12) were elevated, while nestin was diminished in the mitochondrial fraction of A2780-CP20 relative to A2780. This was verified by immunoblot analysis. These results confirm that important changes in the mitochondrial proteome, many of which promote evasion of apoptosis and tumor invasiveness and metastasis, are present in cisplatin-resistant EOC

Myeloperoxidase mediated HDL oxidation and HDL proteome changes do not contribute to dysfunctional HDL in Chinese subjects with coronary artery disease

<div><p>High density lipoprotein (HDL) cholesterol levels and cholesterol efflux capacity (CEC) are inversely correlated with coronary artery disease (CAD) risk. Myeloperoxidase (MPO) derived oxidants and HDL proteome changes are implicated in HDL dysfunction in subjects with CAD in the United States; however, the effect of MPO on HDL function and HDL proteome in ethnic Chinese population is unknown. We recruited four matched ethnic Chinese groups (20 patients each): subjects with 1) low HDL levels (HDL levels in men <40mg/dL and women <50mg/dL) and non-CAD (identified by coronary angiography or cardiac CT angiography); 2) low HDL and CAD; 3) high HDL (men >50mg/dL; women >60mg/dL) with no CAD; and 4) high HDL with CAD. Serum cytokines, serum MPO levels, serum CEC, MPO-oxidized HDL tyrosine moieties, and HDL proteome were assessed by mass spectrometry individually in the four groups.</p><p>The cytokines, MPO levels, and HDL proteome profiles were not significantly different between the four groups. As expected, CEC was depressed in the entire CAD group but more specifically in the CAD low-HDL group. HDL of CAD subjects had significantly higher 3-nitrotyrosine than non-CAD subjects, but the MPO-specific 3-chlorotyrosine was unchanged; CEC in the CAD low-HDL group did not correlate with either HDL 3-chlorotyrosine or 3-nitrotyrosine levels. Neither 3-chlorotyrosine, which is MPO-specific, nor 3-nitrotyrosine generated from MPO or other reactive nitrogen species was associated with CEC. MPO mediated oxidative stress and HDL proteome composition changes are not the primary cause HDL dysfunction in Chinese subjects with CAD. These studies highlight ethnic differences in HDL dysfunction between United States and Chinese cohorts raising possibility of unique pathways of HDL dysfunction in this cohort.</p></div

Cholesterol efflux capacity is decreased in coronary artery disease patients in China.

<p>(A) Cholesterol efflux capacity (CEC) in coronary artery disease (CAD) subjects compared to healthy controls (Non CAD) cohort in the entire cohort. (B) CEC shows differences in the CAD and non CAD cohort in the Low HDL group only and (C) shows differences in the high HDL cohort only. CEC is decreased in CAD group overall and specifically in the low HDL cohort, even as the high HDL cohort showed no differences between the CAD and non CAD group (*p value<0.05).</p

Plasma myeloperoxidase (MPO) levels and activity are unchanged in coronary artery disease patients in China.

<p>Plasma MPO levels in subjects with coronary artery disease (CAD) and without CAD (Non CAD) are represented by box plots of (A) All subjects (n = 40/group), (B) Low HDL subjects alone (n = 20/group) and (C) High HDL subjects alone (n = 20/group). MPO activity is represented by high density lipoprotein (HDL) 3-chlorotyrosine and 3-nitrotyrosine levels normalized to tyrosine levels determined by tandem mass spectrometry. Box plots display the distributions of HDL levels (log scale; log) of 3-chlorotyrosine in (D) All subjects (n = 40/group), (E) Low HDL subjects only (n = 20/group) and (F) High HDL subjects only (n = 20/group) between CAD and Non CAD groups. HDL 3-nitrotyrosine levels represented by box plot (log scale, log) of (G) All subjects (n = 40/group), (H) Low HDL subjects only (n = 20/group), and (I) High HDL subjects only (n = 20/group) between CAD and Non CAD groups. The plasma levels of MPO were not different between CAD and Non CAD subjects in the different cohorts. The HDL 3 chlorotyrosine levels were not different between groups except in the Low HDL subjects were the HDL 3-chlorotyrosine levels were elevated in the CAD subjects than in the non CAD subjects. The HDL 3-nitrotyrosine levels were elevated in the CAD subjects in the entire cohort and in both the low and high HDL subjects. The length of the box defines the interquartile range (IQR). Medians are reported for each group on the raw scale above the respective bar graphs. *denotes p<0.05.</p

High-density lipoprotein protein composition is not altered in Chinese coronary artery disease subjects irrespective of high-density lipoprotein levels.

<p>The relative enrichment of 25 proteins in the high density lipoprotein (HDL) fraction of with and without coronary artery disease (CAD, Non CAD; n = 10 each) is represented by peptide index as described in the Methods section. No significant changes were observed between CAD and Non CAD subjects in both the cohorts. ALB-Albumin; A1AT-Alpha 1 antitrypsin; APO E-Apolipoprotein E; APOA1-Apolipoprotein A-I; APOA2-Apolipoprotein A-II; APOA4-Apolipoprotein A-IV; APOB-Apolipoprotein B; APOC1-Apolipoprotein C1; APOC2-Apolipoprotein C-II; APOC3-Apolipoprotein C3; APOC4- Apolipoprotein C-IV; APOD- Apolipoprotein D; APOF-Apolipoprotein F; C4A-Complement fragment 4A; C9-Complement 3; CETP-Cholesterol Ester transfer protein; CLU-Clusterin; FGA-Fibrinogen alpha; PCYOX1-Prenylcysteine oxidase 1; PLA2G7-Platelet-Activating Factor Acetylhydrolase; PLTP-Phospholipid transfer protein; PON1-Serum paraoxonase/arylesterase 1; SAA-Serum Amyloid A protein; SHBG- Sex hormone-binding globulin; VTN-Vitronectin.</p