scholarly journals P-Selectin- and CD63-Exposing Platelet Microparticles Reflect Platelet Activation in Peripheral Arterial Disease and Myocardial Infarction

2006 ◽  
Vol 52 (4) ◽  
pp. 657-664 ◽  
Author(s):  
P Marc van der Zee ◽  
Éva Biró ◽  
Yung Ko ◽  
Robbert J de Winter ◽  
C Erik Hack ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Peripheral Arterial Disease ◽  
Platelet Activation ◽  
Plasma Concentrations ◽  
Arterial Disease ◽  
Thrombin Receptor ◽  
Ionophore A23187 ◽  
St Elevation ◽  
Peripheral Arterial

Abstract Background: Platelet-derived microparticles (PMPs) are generally considered a marker of platelet activation in cardiovascular disease. We studied the extent to which PMP subpopulations parallel platelet activation in vitro and in vivo. Methods: Using flow cytometry, we analyzed PMP subpopulations from resting and activated platelets in vitro (n = 6) as well as from plasma samples of patients with stable angina, peripheral arterial disease, or myocardial infarction [non-ST-elevation (NSTEMI) and ST-elevation (STEMI)] and from older, age- and sex-matched and young healthy individuals [n = 10 for all groups except NSTEMI (n = 11)]. Coagulation markers prothrombin fragment F1 + 2 and thrombin-antithrombin complexes were determined by ELISA. The PMP-associated fraction of soluble (s)P-selectin was estimated by ELISA. Results: In vitro, stimulation of platelets with thrombin receptor–activating peptide (15 μmol/L) or the calcium ionophore A23187 (2.5 μmol/L) increased fractions of both platelets and PMPs exposing P-selectin or CD63 (P <0.001 for all). Whereas the number of PMPs released by A23187-stimulated platelets increased significantly (P <0.001), the number of PMPs released from thrombin receptor-activating peptide–stimulated platelets remained constant (P >0.05). Ex vivo, numbers of circulating PMPs were comparable in all groups. Compared with young persons, P-selectin–exposing PMPs were increased in older persons (P = 0.02) and were further increased in patients with NSTEMI (P = 0.007) and STEMI (P = 0.045). CD63-exposing PMPs were increased in patients with peripheral arterial disease (P = 0.041), NSTEMI (P = 0.001), and STEMI (P = 0.049). Subpopulations exposing P-selectin or CD63 correlated with each other (r = 0.581; P <0.001), but neither correlated with the plasma concentrations of F1 + 2 or thrombin–antithrombin complexes. The PMP-associated fraction of sP-selectin constituted only 2.2 (4.7)% [mean (SD)] of total sP-selectin. Conclusions: PMP subpopulations reflect platelet activation status better than the total number of PMPs. Increased concentrations of circulating PMP subpopulations are found in aging, and further increases are encountered in peripheral arterial disease and myocardial infarction.

Platelet activation during treadmill exercise in patients with chronic peripheral arterial disease

1981 ◽  
Vol 23 (3) ◽  
pp. 215-223 ◽  
Author(s):  
G Baele ◽  
H Bogaerts ◽  
D.L Clement ◽  
R Pannier ◽  
F Barbier
Keyword(s):  
Peripheral Arterial Disease ◽  
Platelet Activation ◽  
Treadmill Exercise ◽  
Arterial Disease ◽  
Peripheral Arterial

Abstract P081: Markers of Endothelial Function and Peripheral Arterial Disease among Women

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Sona Rivas-Tumanyan ◽  
Kenneth J Mukamal ◽  
Jennifer K Pai ◽  
Kaumudi J Joshipura
Keyword(s):  
Myocardial Infarction ◽  
Peripheral Arterial Disease ◽  
Endothelial Function ◽  
Conditional Logistic Regression ◽  
Relative Weight ◽  
Serum Levels ◽  
Arterial Disease ◽  
Blood Draw ◽  
Increased Risk ◽  
Peripheral Arterial

Introduction: Markers of endothelial function may be associated with increased risk for cardiovascular disease; however, prospective data for peripheral arterial disease (PAD) are limited. We evaluated the hypothesis that serum markers of endothelial dysfunction are associated with an increased risk of PAD among women. Methods: We conducted a nested case-control study within an ongoing prospective cohort of U.S. female nurses (Nurses’ Health Study). Among 32,826 NHS participants who provided blood samples in 1989-1990, after excluding those who had myocardial infarction, coronary heart disease, stroke, or carotid artery surgery prior to the PAD diagnosis, we included all incident PAD cases that occurred between 1990 and 2008 and were confirmed by medical records. Each case was individually matched with three eligible controls using risk-set sampling, by age, smoking, date of blood draw, and fasting status. We evaluated the association between serum levels of soluble intercellular adhesion molecule (ICAM-1), E-selectin, and the risk of PAD, using conditional logistic regression analysis. Results: Complete biomarker data from 1990 was available for 144 cases and 431 controls. After accounting for matching factors, baseline ICAM-1 levels were associated with higher risk of PAD (RR for highest (T3) vs. lowest (T1) tertile=1.75, 95% CI: 1.05-2.90). The association was attenuated and no longer significant (RR T3 vs. T1=1.37, 95% CI: 0.75-2.49) after adjusting for serum levels of HDL and LDL-cholesterol, family history of myocardial infarction, relative weight, reported aspirin and cholesterol-lowering medication use, hypertension and diabetes diagnoses, physical activity, and pack-years of smoking. Additional adjustment for CRP levels further attenuated the relative risk (RR T3 vs. T1= 1.24, 95% CI: 0.67-2.29). We did not observe any significant association between baseline E-selectin levels and the risk of PAD (multivariate- and CRP-adjusted RR T3 vs. T1=0.93, 95% CI: 0.54-1.59). Conclusions: There was no association between ICAM-1 and E-selectin and subsequent PAD in this cohort of U.S women.

Abstract 17797: Noninvasive Optical Imaging of Response to On-Demand Antioxidant Therapy in a Model of Peripheral Arterial Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Kristin M Poole ◽  
Christopher E Nelson ◽  
John R Martin ◽  
Devin R McCormack ◽  
Rucha V Joshi ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Hyperspectral Imaging ◽  
Time Course ◽  
Arterial Disease ◽  
Diameter Distribution ◽  
Novel Therapy ◽  
On Demand ◽  
Vessel Morphology ◽  
Peripheral Arterial

Peripheral arterial disease is often modeled by surgical induction of hind limb ischemia (HLI) in mice to study collateral vessel development. However, there is a need for methodologies that provide intravital, multifunctional, quantitative data on ischemic recovery for robust evaluation of new therapeutics. Here, we apply hyperspectral imaging and optical coherence tomography (OCT) to longitudinally assess hemoglobin oxygen saturation (SaO 2 ) and vessel morphology in response to a novel therapy. Injectable microspheres loaded with curcumin were synthesized from reactive oxygen species (ROS)-responsive poly(propylene) sulfide (PPS) to provide “on demand”, local release of the antioxidant drug curcumin to reduce tissue-damaging oxidative stress in a mouse model of diabetic HLI. Curcumin-PPS microspheres significantly reduced intracellular ROS in LPS-activated RAW 264.7 macrophages and rescued viability of 3T3 fibroblasts treated with cytotoxic levels of H 2 O 2 in vitro . HLI was induced in FVB mice with streptozotocin-induced diabetes, and curcumin-PPS or blank-PPS microspheres were injected into the ischemic limb. Curcumin-PPS significantly improved recovery of SaO 2 in the ischemic footpad relative to blank-PPS and vehicle (saline) groups over a one week time course evaluated with hyperspectral imaging (n≥8/group, p<0.05). Vessel structure in the gastrocnemius was imaged noninvasively with OCT at day 7 (Figure), revealing trends toward increased vessel area density and vessel length fraction in the curcumin-PPS group (n=5/group). The vessel diameter distribution was also extracted from OCT data. Our collective data indicate that sustained, on demand curcumin delivery has significant therapeutic promise for improving ischemic tissue recovery. Also, the hyperspectral and OCT imaging methods showcased provide quantitative, noninvasive monitoring of vasculature and can accelerate screening of novel therapies.

Abstract 53: Ablation of Thrombin Signaling in Platelets but Not in Endothelial Cells Impairs Hemostasis in a Mouse Model of Spontaneous Gastrointestinal Bleeding

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Stephen J Wilson ◽  
Maria M Stevens ◽  
Shaun R Coughlin
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cells ◽  
Platelet Activation ◽  
Bleeding Risk ◽  
Arterial Disease ◽  
Gi Bleeding ◽  
Intestinal Polyposis ◽  
Wild Type ◽  
Spontaneous Bleeding ◽  
Peripheral Arterial

Human PAR1 is expressed in endothelial cells as well as in platelets where it facilitates the response to thrombin and platelet activation. Vorapaxar, a PAR1 antagonist, prevents myocardial infarction and stroke in patients with prior MI or peripheral arterial disease at a cost of increased bleeding risk. Par1 is also highly expressed in endothelial cells in mice, and Par1-deficiency is associated with bleeding in the mouse embryo at midgestation. Additionally, known actions of endothelial PAR1 activation suggest pro-hemostatic functions. This raises the question of whether inhibition of PAR1 function in endothelial cells (in addition to PAR1 inhibition in platelets) contributes to the bleeding risk associated with Vorapaxar treatment. Our previous work demonstrated that Par1 deficiency results in loss of thrombin signaling in mouse endothelial cells but not mouse platelets, while Par4 deficiency ablated thrombin-induced platelet activation in mice. Thus, mice allow us to separate loss of thrombin signaling in platelets from loss of thrombin signaling in endothelial cells. Accordingly, we used Apc min/+ mice, which develop intestinal polyposis and spontaneous GI bleeding, as a model to determine whether loss of thrombin signaling in platelets (Par4 KO) or endothelial and other cells (Par1 KO) exacerbates spontaneous bleeding. Hematocrit and other hematologic parameters were measured biweekly from 7 weeks through 15 weeks of age. Hematocrits in mice wild-type for Apc were stable over this period (41.48 ± 0.48 at 7 weeks; 40.48 ± 0.37 at 15 weeks, n=15). Hematocrits in Apc min/+ mice fell approximately linearly from 37.06 ± 0.82 at 7 weeks to 14.39 ± 1.12 at 15 weeks (n=15). Hematocrits in Par1-deficient Apc min/+ mice were indistinguishable from those in Apc min/+ without Par deficiency (14.39 ± 1.12 vs 14.47 ± 1.66 at 15 weeks; n=6-15). By contrast, Par4-deficient Apc min/+ mice were already severely anemic at 7 weeks compared to Apc min/+ mice (19 ± 2.0 vs 39 ± 3.6; p<0.01, n=4). Par-dependent differences in polyp count and size were not detected. Taken together, our results suggest that loss of thrombin signaling in platelets promotes spontaneous GI bleeding in the Apc min model while loss of thrombin signaling in endothelial cells is without effect in this system.

scholarly journals Peripheral Arterial Disease in Patients Presenting with Acute Coronary Syndrome in Six Middle Eastern Countries

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Hassan A. Al-Thani ◽  
Ayman El-Menyar ◽  
Mohammad Zubaid ◽  
Wafa A. Rashed ◽  
Mustafa Ridha ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Peripheral Arterial Disease ◽  
Middle Eastern ◽  
Arterial Disease ◽  
High Risk Group ◽  
Hospital Death ◽  
Gulf Region ◽  
Coronary Syndrome ◽  
St Elevation ◽  
Peripheral Arterial

To describe prevalence and impact of peripheral arterial disease (PAD) in patients with acute coronary syndrome (ACS), data were collected over 5 months from 6 Middle Eastern countries. Patients were divided into 2 groups (with and without PAD). Out of 6705 consecutive ACS patients, PAD was reported in 177 patients. In comparison to non-PAD, PAD patients were older and more likely to have cardiovascular risk factors. They were more likely to have high Killip class, high GRACE risk score, and non-ST elevation ACS (NSTEACS) at presentation. Thrombolytics, antiplatelet use, and coronary intervention were comparable in both groups. When presented with ST-elevation myocardial infarction (STEMI), patients with PAD had worse outcomes, while in NSTEACS; PAD was associated with higher rate of heart failure in comparison to non-PAD patients. In diabetics, PAD was associated with 2-fold increase in mortality when compared to non-PAD (P=0.028). After adjustment, PAD was associated with high mortality in STEMI (adjusted OR 2.6; 95% CI 1.23–5.65,P=0.01). Prevalence of PAD in ACS in the Gulf region is low. Patients with PAD and ACS constitute a high risk group and require more attention. PAD in patients with STEMI is an independent predictor of in-hospital death.

Abstract 5281: Bioluminescence Imaging of X-Ray Visible Microencapsulated Mesenchymal Stem Cells for Cell Based Therapy of Peripheral Arterial Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Dorota A Kedziorek ◽  
Piotr Walczak ◽  
Yingli Fu ◽  
Nicole Azene ◽  
Aravind Arepally ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
X Ray ◽  
Encapsulated Cells ◽  
X Ray Imaging ◽  
Peripheral Arterial

Introduction: Therapeutic angiogenesis in Peripheral Arterial Disease (PAD) using stem cell therapy is potentially complicated by immunorejection. To overcome this problem, microen-capsulation using the alginate-poly-L-lysine (PLL)-alginate (APA) method was developed to provide a protective porous bubble to block antibodies but allow exchange of small molecules. Recently, we have developed a method to enable X-ray detection of these capsules. However, cell survival within the capsules could not be determined. Plus PLL can be mildly cytotoxic. In the present study, we combined reporter gene methods to verify cell survival with X-ray detection of the microcapsules in a rabbit PAD model and studied the PLL impact on cell viability. Methods: Rabbit mesenchymal stem cells (MSCs) were transfected with triple fusion (TF) reporter gene for bioluminescence (firefly luciferase), fluorescence (red fluorescent protein) and PET (truncated thymidine kinase). TF-MSCs were encapsulated in the perfluorooctyl bromide (PFOB) capsules to enable computed tomographic detection. Capsule crosslinking was performed with three PLL concentrations, i.e., 0.005%, 0.025% and 0.05%. Bioluminescent imaging (BLI) was used to monitor cells survival for one week in vitro and after intramuscular injection in vivo . Results: Serial in vitro BLI enabled the detection of viable encapsulated MSCs without detrimental signal degradation (~13% decrease of BLI signal intensity after PFOB encapsulation comparing to equal number of naked MSCs). PLL did not result in cell death; higher PLL concentrations were correlated with stronger BLI signal. BLI signal production was only slightly reduced by second layer of alginate (~80% for 0.05% PLL). In vivo BLI demonstrated the detection of naked, APA, and PFOB-encapsulated TF-MSCs. X-ray imaging enabled PFOB microcapsules detection relative to vasculature. Conclusion: BLI allows monitoring of encapsulated cells survival. PLL concentrations ≤ 0.05% appear safe for encapsulated cells with higher concentration being associated with enhanced crosslinking and capsule stability. MSCs expressing TF reporter in PFOB microcapsules enables dual monitoring of cell delivery/capsule tracking by X-ray imaging and cell viability with BLI.

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