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1.  Peripheral artery disease, biomarkers, and darapladib 
American heart journal  2011;161(5):972-978.
Subjects with peripheral artery disease (PAD) are at increased risk of cardiovascular morbidity and mortality, perhaps in part, related to increased levels of inflammation, platelet activity, and lipids. We therefore sought to investigate the relationship between PAD and levels of inflammatory, platelet, and lipid biomarkers and the treatment effect of darapladib, a novel lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor.
This is a post hoc analysis of the 959 patients with coronary disease or their risk equivalent receiving atorvastatin who were randomized to receive darapladib or placebo to examine the effects of an Lp-PLA2 inhibitor on the biomarkers of cardiovascular risk. We conducted an exploratory analysis evaluating the levels of biomarkers in subjects with PAD (n = 172) compared with those without PAD (n = 787).
After adjustment for age, sex, smoking, body mass index, and diabetes, subjects with PAD had greater levels of matrix metalloproteinase-9 (between group comparisons 22%, 95% confidence interval [10–31], P < .01), myeloperoxidase (12% [2–20], P = .01), interleukin-6 (13% [4–21], P = .01), adiponectin (17% [7–26], P < .01), intercellular adhesion molecule-1 (7% [2–11], P < .01), osteoprotegrin (6% [1–10], P = .02), CD40 ligand (15% [1–28], P = .04), high-sensitivity C-reactive protein (17% [1–31], P = .04), and triglycerides (11% [0.2–21], P = .05). No significant difference was detected for Lp-PLA2 activity, P-selectin, urinary 11-dehydrothroboxane B2, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol between subjects with and without PAD. Darapladib produced highly significant inhibition of Lp-PLA2 activity when compared with placebo at weeks 4 and 12 (P < .01) in patients with and without PAD.
Subjects with PAD had elevated levels of matrix metalloproteinase-9, myeloperoxidase, interleukin-6, adiponectin, intercellular adhesion molecule-1, osteoprotegrin, CD40 ligand, high-sensitivity C-reactive protein, and triglycerides compared with those without PAD. Darapladib, a novel Lp-PLA2 inhibitor, was equally effective in reducing Lp-PLA2 activity levels in subjects with and without PAD.
PMCID: PMC3750980  PMID: 21570531
2.  Centrifugation Speed Affects Light Transmission Aggregometry 
Light transmission aggregometry (LTA) is considered the gold-standard for investigating platelet activity ex vivo. However, LTA protocols are not standardized and differences in LTA procedure are a potential source of variance in results. Centrifugation speed is an essential component of platelet preparation in LTA, has yet to be standardized, and may affect platelet aggregation results. We sought to investigate the effect of relative centrifugal force (RCF) intensity on LTA results.
Ten healthy controls had venous blood drawn and centrifuged at 150g, 200g, 300g, and 500g for 10 minutes. Cell counts in whole blood and PRP were measured using a hematology analyzer. LTA was performed using 1.0uM ADP and 0.4uM epinephrine as an agonist. Aggregation (%) was compared at 60, 120, 180, and 300 seconds (s) and at maximum aggregation.
Centrifugation speed was associated with decreasing platelet count (P<0.001) and decreasing MPV (P<0.001) in platelet rich plasma. Maximum aggregation decreased with increasing speeds for ADP 1.0uM (150g-89%, 200g-93%, 300g-71%, 500g-17%; P<0.001). Similar findings were noted at 120s (150g-69%, 200g-50%, 300g-35%, 500g-12%; P<0.001), 180s (150g-82%, 200g-74%, 300g-44%, 500g-13%; P<0.001), and 300s (150g-85%, 200g-88%, 300g-55%, 500g-14%; P<0.001). Consistently, platelet aggregation in response to epinephrine 0.4uM decreased significantly with increasing centrifuge RCF at 60s, 120s, 180s, 300s, and at maximum aggregation (P<0.05 for each comparison).
Our data demonstrate the importance of centrifugation speed in the interpretation of LTA results, supporting the need for standardization of centrifugation RCF in LTA protocols.
PMCID: PMC3209490  PMID: 21794095
Light transmission aggregometry; Methodology; Centrifuge; Platelets
3.  Oxidative Stress and Inflammation in Renal Patients and Healthy Subjects 
PLoS ONE  2011;6(7):e22360.
The first goal of this study was to measure the oxidative stress (OS) and relate it to lipoprotein variables in 35 renal patients before dialysis (CKD), 37 on hemodialysis (HD) and 63 healthy subjects. The method for OS was based on the ratio of cholesteryl esters (CE) containing C18/C16 fatty acids (R2) measured by gas chromatography (GC) which is a simple, direct, rapid and reliable procedure. The second goal was to investigate and identify a triacylglycerol peak on GC, referred to as TG48 (48 represents the sum of the three fatty acids carbon chain lengths) which was markedly increased in renal patients compared to healthy controls. We measured TG48 in patients and controls. Mass spectrometry (MS) and MS twice in tandem were used to analyze the fatty acid composition of TG48. MS showed that TG48 was abundant in saturated fatty acids (SFAs) that were known for their pro-inflammatory property. TG48 was significantly and inversely correlated with OS. Renal patients were characterized by higher OS and inflammation than healthy subjects. Inflammation correlated strongly with TG, VLDL-cholesterol, apolipoprotein (apo) C-III and apoC-III bound to apoB-containing lipoproteins, but not with either total cholesterol or LDL-cholesterol.
In conclusion, we have discovered a new inflammatory factor, TG48. It is characterized with TG rich in saturated fatty acids. Renal patients have increased TG48 than healthy controls.
PMCID: PMC3145638  PMID: 21829457
4.  Maternal Arterial Stiffness in Women Who Subsequently Develop Pre-Eclampsia 
PLoS ONE  2011;6(5):e18703.
Pre-eclampsia (PE) is associated with profound changes in the maternal cardiovascular system. The aim of the present study was to assess whether alterations in the maternal arterial stiffness precede the onset of PE in at risk women.
Methodology/Principal Findings
This was a cross sectional study involving 70 pregnant women with normal and 70 women with abnormal uterine artery Doppler examination at 22–24 weeks of gestation. All women had their arterial stiffness (augmentation index and pulse wave velocity of the carotid-femoral and carotid-radial parts of the arterial tree) assessed by applanation tonometry in the second trimester of pregnancy, at the time of the uterine artery Doppler imaging. Among the 140 women participating in the study 29 developed PE (PE group) and 111 did not (non-PE group). Compared to the non-PE group, women that developed PE had higher central systolic (94.9±8.6 mmHg vs 104.3±11.1 mmHg; p = <0.01) and diastolic (64.0±6.0 vs 72.4±9.1; p<0.01) blood pressures. All the arterial stiffness indices were adjusted for possible confounders and expressed as multiples of the median (MoM) of the non-PE group. The adjusted median augmentation index was similar between the two groups (p = 0.84). The adjusted median pulse wave velocities were higher in the PE group compared to the non-PE group (carotid-femoral: 1.10±0.14 MoMs vs 0.99±0.11 MoMs; p<0.01 and carotid-radial: 1.08±0.12 MoMs vs 1.0±0.11 MoMs; p<0.01).
Increased maternal arterial stiffness, as assessed by pulse wave velocity, predates the development of PE in at risk women.
PMCID: PMC3086903  PMID: 21559278

Results 1-4 (4)