bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic Analysis of Intraluminal Thrombus Highlights Complement Activation in Human Abdominal Aortic Aneurysms
Authors: Martinez-Pinna Roxana , Madrigal-Matute Julio , Tarin Carlos , Burillo Elena , Esteban-Salan Margarita , Pastor-Vargas Carlos , Lindholt Jes S. , Lopez Juan A. , Calvo Enrique , de Ceniga Melina Vega , Meilhac Olivier , Egido Jesus , Blanco-Colio Luis M. , Michel Jean-Baptiste , Martin-Ventura Jose L. 
Published: May 2013

Objective—
To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA).

Approach and Results—
Tissue-conditioned media from patients with AAA were analyzed by a mass spectrometry–based strategy using liquid chromatography coupled to tandem mass spectrometry. Global pathway analysis by Ingenuity software highlighted the presence of several circulating proteins, among them were proteins from the complement system. Complement C3 concentration and activation were assessed in plasma from AAA patients (small AAA, AAA diameter=3–5 cm and large AAA, AAA diameter >5 cm), showing decreased C3 levels and activation in large AAA patients. No association of a combination of single-nucleotide polymorphisms in complement genes between large and small AAA patients was observed. Intense extracellular C3 inmunostaining, along with C9, was observed in AAA thrombus. Analysis of C3 in AAA tissue homogenates and tissue-conditioned media showed increased levels of C3 in AAA thrombus, as well as proteolytic fragments (C3a/C3c/C3dg), suggesting its local deposition and activation. Finally, the functional role of local complement activation in polymorphonuclear (PMN) cell activation was tested, showing that C3 blockade by anti-C3 antibody was able to decrease thrombus-induced neutrophil chemotaxis and reactive oxygen species production.

Conclusions—
A decrease of systemic C3 concentration and activity in the later stages of AAA associated with local complement retention, consumption, and proteolysis in the thrombus could induce PMN chemotaxis and activation, playing a detrimental role in AAA progression.
Stent Placement Versus Balloon Angioplasty for the Treatment of Obstructive Lesions of the Popliteal Artery
Authors: Rastan Aljoscha , Krankenberg Hans , Baumgartner Iris , Blessing Erwin , Müller-Hülsbeck Stefan , Pilger Ernst , Scheinert Dierk , Lammer Johannes , Gißler Martin , Noory Elias , Neumann Franz-Josef , Zeller Thomas 
Published: May 2013

Background—
Stenting has been shown to improve patency after femoral artery revascularization compared with balloon angioplasty. Limited data are available evaluating endovascular treatment for obstructive lesions of the popliteal artery.

Methods and Results—

This prospective, randomized, multicenter trial compared primary nitinol stent placement to percutaneous transluminal balloon angioplasty in patients with peripheral artery disease Rutherford-Becker class 2 to 5 who had a de novo lesion in the popliteal artery. The primary study end point was 1-year primary patency, defined as freedom from target-lesion restenosis (luminal narrowing of ≥50%) as detected by duplex ultrasound. Secondary end points included target-lesion revascularization rate and changes in Rutherford-Becker class. Provisional stent placement was considered target-lesion revascularization and loss of primary patency. Two hundred forty-six patients were included in this trial. The mean target-lesion length was 42.3 mm. One hundred ninety-seven patients were available for the1-year follow-up. The 1-year primary patency rate was significantly higher in the group with primary nitinol stent placement (67.4%) than in the percutaneous transluminal balloon angioplasty group (44.9%,
P
=0.002). Target-lesion revascularization rates were 14.7% and 44.1%, respectively (
P
=0.0001); however, when provisional nitinol stent placement was not considered target-lesion revascularization and loss in patency, no significant differences prevailed between the study groups (67.4% versus 65.7%,
P
=0.92 for primary patency). Approximately 73% of patients in the percutaneous transluminal balloon angioplasty group and 77% in the nitinol stent group showed an improvement of ≥1 Rutherford-Becker class (
P
=0.31).

Conclusions—
Primary nitinol stent placement for obstructive lesions of the popliteal artery achieves superior acute technical success and higher 1-year primary patency only if provisional stenting is considered target-lesion revascularization. Provisional stenting as part of a percutaneous transluminal balloon angioplasty strategy has equivalent 1-year patency and should be preferred over primary stenting.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00712309.
Evidence That Acetylsalicylic Acid Attenuates Inflammation in the Walls of Human Cerebral Aneurysms: Preliminary Results
Authors: Hasan David M. , Chalouhi Nohra , Jabbour Pascal , Dumont Aaron S. , Kung David K. , Magnotta Vincent A. , Young William L. , Hashimoto Tomoki , Richard Winn H. , Heistad Donald 
Published: May 2013

Background

Inflammatory cells and molecules may play a critical role in formation and rupture of cerebral aneurysms. Recently, an epidemiologic study reported that acetylsalicylic acid (
ASA
) decreases the risk of aneurysm rupture. The goal of this study was to determine the effects of
ASA
on inflammatory cells and molecules in the walls of human cerebral aneurysms, using radiographic and histological techniques.

Methods and Results

Eleven prospectively enrolled patients harboring unruptured intracranial aneurysms were randomized into an
ASA
‐treated (81 mg daily) group (n=6) and an untreated (control) group (n=5). Aneurysms were imaged at baseline using ferumoxytol‐enhanced
MRI
to estimate uptake by macrophages. After 3 months, patients were reimaged before undergoing microsurgical clipping. Aneurysm tissues were collected for immunostaining with monoclonal antibodies for cyclooxygenase‐1 (
COX
‐1), cyclooxygenase‐2 (
COX
‐2), microsomal prostaglandin E2 synthase‐1 (
mPGES
‐1), and macrophages. A decrease in signal intensity on ferumoxytol‐enhanced
MRI
was observed after 3 months of
ASA
treatment. Expression of
COX
‐2 (but not
COX
‐1),
mPGES
‐1, and macrophages was lower in the
ASA
group than in the control group.

Conclusions

This study provides preliminary radiographical and histological evidence that
ASA
may attenuate the inflammatory process in the walls of human cerebral aneurysms.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01710072.
Simple Risk Model Predicts Incidence of Atrial Fibrillation in a Racially and Geographically Diverse Population: the CHARGE‐AF Consortium
Authors: Alonso Alvaro , Krijthe Bouwe P. , Aspelund Thor , Stepas Katherine A. , Pencina Michael J. , Moser Carlee B. , Sinner Moritz F. , Sotoodehnia Nona , Fontes João D. , Janssens A. Cecile J. W. , Kronmal Richard A. , Magnani Jared W. , Witteman Jacqueline C. , Chamberlain Alanna M. , Lubitz Steven A. , Schnabel Renate B. , Agarwal Sunil K. , McManus David D. , Ellinor Patrick T. , Larson Martin G. , Burke Gregory L. , Launer Lenore J. , Hofman Albert , Levy Daniel , Gottdiener John S. , Kääb Stefan , Couper David , Harris Tamara B. , Soliman Elsayed Z. , Stricker Bruno H. C. , Gudnason Vilmundur , Heckbert Susan R. , Benjamin Emelia J. 
Published: May 2013

Background

Tools for the prediction of atrial fibrillation (
AF
) may identify high‐risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors.

Methods and Results

Individual‐level data from 3 large cohorts in the
U
nited
S
tates (Atherosclerosis Risk in Communities [
ARIC
] study, the Cardiovascular Health Study [
CHS
], and the Framingham Heart Study [
FHS
]), including 18 556 men and women aged 46 to 94 years (19%
A
frican
A
mericans, 81% whites) were pooled to derive predictive models for
AF
using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment—Reykjavik study (
AGES
) and the Rotterdam Study (
RS
). The analysis included 1186 incident
AF
cases in the derivation cohorts and 585 in the validation cohorts. A simple 5‐year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C‐statistic, 0.765; 95%
CI
, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C‐statistic, 0.767; 95%
CI
, 0.750 to 0.783; categorical net reclassification improvement, −0.0032; 95%
CI
, −0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (
AGES
C‐statistic, 0.664; 95%
CI
, 0.632 to 0.697 and
RS
C‐statistic, 0.705; 95%
CI
, 0.664 to 0.747) and calibration was adequate.

Conclusion

A risk model including variables readily available in primary care settings adequately predicted
AF
in diverse populations from the
U
nited
S
tates and
E
urope.
Relationship of Plasma Galectin‐3 to Renal Function in Patients With Heart Failure: Effects of Clinical Status, Pathophysiology of Heart Failure, and Presence or Absence of Heart Failure
Authors: Gopal Deepa M. , Kommineni Maya , Ayalon Nir , Koelbl Christian , Ayalon Rivka , Biolo Andreia , Dember Laura M. , Downing Jill , Siwik Deborah A. , Liang Chang‐seng , Colucci Wilson S. 
Published: May 2013

Background

Galectin‐3 (
GAL
‐3), a β‐galactoside–binding protein, is a new clinical biomarker believed to reflect cardiac remodeling/fibrosis in patients with heart failure (
HF
). Plasma
GAL
‐3 is inversely related to renal function. It is not known whether the relationship between renal function and
GAL
‐3 is influenced by clinical decompensation, type of
HF
, or the presence or absence of clinical
HF
.

Methods and Results

Patients were prospectively categorized as having acute decompensated
HF
or stable
HF
on the basis of clinical status and as having HF with reduced left ventricular ejection fraction or HF with preserved left ventricular ejection fraction. Plasma
GAL
‐3 was measured by enzyme‐linked immunosorbent assay in patients with
HF
(n=75), control patients without
HF
(n=32), and control patients without
HF
with moderate renal insufficiency (n=12). Compared to controls without
HF
(14±4 ng/mL),
GAL
‐3 was higher in patients with both acute decompensated
HF
(23±11 ng/mL) and stable
HF
(22±10 ng/mL) (
P
<0.001 versus controls for both) but did not differ between acute decompensated
HF
and stable
HF
(
P
=0.75). Likewise,
GAL
‐3 was elevated in both HF with preserved left ventricular ejection fraction (23±9 ng/mL) and HF with reduced left ventricular ejection fraction (22±11 ng/mL) (
P
<0.001 versus controls for both) but did not differ between HF with preserved ejection fraction and HF with reduced ejection fraction (
P
=0.37).
GAL
‐3 correlated strongly with estimated glomerular filtration rate, both in patients with
HF
(
r
=−0.75,
P
<0.001) and in patients without
HF
(
r
=−0.82,
P
<0.001), and this relationship was unaffected by the presence or absence of clinical
HF
.

Conclusions

Plasma
GAL
‐3 is inversely related to renal function in patients with and without clinical
HF
. Concentrations of plasma
GAL
‐3 do not seem to depend on the level of compensation or type of
HF
. Furthermore, the relationship between
GAL
‐3 and renal function seems to be affected little or not at all by the presence or absence of clinical
HF
.
Carotid Atherosclerotic Plaque Matrix Metalloproteinase‐12–Positive Macrophage Subpopulation Predicts Adverse Outcome After Endarterectomy
Authors: Scholtes Vincent P. W. , Johnson Jason L. , Jenkins Nicholas , Sala‐Newby Graciela B. , de Vries Jean‐Paul P. M. , de Borst Gert Jan , de Kleijn Dominique P. V. , Moll Frans L. , Pasterkamp Gerard , Newby Andrew C. 
Published: May 2013

Background

Matrix metalloproteinase‐12 (
MMP
‐12) promotes atherosclerosis in animal models.
MMP
‐12 is expressed in only a subset of foam‐cell macrophages (
FCM
s) in human plaques. We investigated whether the prevalence of this
MMP
‐12–expressing subpopulation is a prognostic indicator of adverse outcome in patients after carotid endarterectomy (
CEA
).

Methods and Results

Serial sections of culprit lesions from 236 patients who underwent
CEA
and had undergone 3 years of clinical follow‐up were stained immunocytochemically for
MMP
‐12 and for
CD
68, and the
MMP
‐12/
CD
68 ratio was used to quantify the
MMP
‐12–expressing subpopulation. A high
MMP
‐12/
CD
68 ratio correlated with a high content of lipid and total macrophages and a low content of vascular smooth muscle cells, as well as with
MMP
‐8 (
R
=0.211,
P
=0.001),
MMP
‐9 (
R
=0.251,
P
<0.001), and cleaved caspase‐3 (
R
=0.142,
P
=0.036) activity measured in a neighboring segment. Dual immunohistochemical examination confirmed the location of
MMP
‐12 in a subpopulation of
MMP
‐8– and
MMP
‐9–positive
FCM
s, whereas all apoptotic
FCM
s were
MMP
‐12 positive. Patients who yielded plaques within the highest quartile compared with the lowest quartile of
MMP
‐12/
CD
68 ratio had a 2.4‐fold (hazard ratio, 2.4; 95% CI, 1.1‐ to 5.1‐fold; adjusted
P
=0.027) increased risk of major adverse cardiovascular event and a 3.4‐fold (3.4; 1.2‐ to 9.6‐fold,
P
=0.024) increased risk for stroke.

Conclusions

The prevalence of an
MMP
‐12–positive subset of
FCM
s is a prognostic marker for adverse clinical outcome after CEA.
Hands‐On Defibrillation Has the Potential to Improve the Quality of Cardiopulmonary Resuscitation and Is Safe for Rescuers— A Preclinical Study
Authors: Neumann Tobias , Gruenewald Matthias , Lauenstein Christoph , Drews Tobias , Iden Timo , Meybohm Patrick 
Published: May 2013

Background

Recently, it has been demonstrated that rescuers could safely provide a low, static downward force in direct contact with patients during elective cardioversion. The purpose of our experimental study was to investigate whether shock delivery during uninterrupted chest compressions may have an impact on cardiopulmonary resuscitation (
CPR
) quality and can be safely performed in a realistic animal model of
CPR
.

Methods and Results

Twenty anesthetized swine were subjected to 7 minutes of ventricular fibrillation followed by CPR according to the 2010
A
merican
H
eart
A
ssociation
G
uidelines. Pregelled self‐adhesive defibrillation electrodes were attached onto the torso in the ventrodorsal direction and connected to a biphasic defibrillator. Animals were randomized either to (1) hands‐on defibrillation, where rescuers wore 2 pairs of polyethylene gloves and shocks were delivered during ongoing chest compressions, or (2) hands‐off defibrillation, where hands were taken off during defibrillation.
CPR
was successful in 9 out of 10 animals in the hands‐on group (versus 8 out of 10 animals in the hands‐off group; not significant). In the hands‐on group, chest compressions were interrupted for 0.8% [0.6%; 1.4%] of the total
CPR
time (versus 8.2% [4.2%; 9.0%];
P
=0.0003), and coronary perfusion pressure was earlier restored to its pre‐interruption level (
P
=0.0205). Also, rescuers neither sensed any kind of electric stimulus nor did
H
olter
ECG
reveal any serious cardiac arrhythmia.

Conclusions

Hands‐on defibrillation may improve
CPR
quality and could be safely performed during uninterrupted chest compressions in our standardized porcine model.
Ablation for Atrial Fibrillation in Combination With Left Atrial Appendage Closure: First Results of a Feasibility Study
Authors: Swaans Martin J. , Post Martijn C. , Rensing Benno J.W.M. , Boersma Lucas V.A. 
Published: May 2013

Background

Drug‐refractory atrial fibrillation (
AF
) increasingly is being treated with catheter ablation. However, the long‐term success rate, expressed as freedom from
AF
, is <50%. Therefore, vitamin K antagonists, with all their complications, remain necessary. Recently, left atrial appendage (
LAA
) occlusion devices were introduced as an alternative to vitamin K antagonists. Here, we investigated whether
AF
ablation and
LAA
occlusion could be a feasible and safe combination in patients with symptomatic drug‐refractory
AF
and a
CHADS
2
score ≥1 or a contraindication for vitamin K antagonists.

Methods and Results

Ablation was performed by using multielectrode catheters with phased radiofrequency energy.
LAA
was occluded with the Watchman device (Atritech, Inc, Plymouth, MN). Between February 2010 and February 2011, 30 patients were treated (21 male; age, 62.8±8.5 years). Median
CHADS
2
score was 2.5 (25th to 75th percentiles: 2 to 3), median
CHADS
‐
VAS
c score was 3 (25th to 75th percentiles: 3 to 5), 77% had prior stroke, and 27% had a contraindication for vitamin K antagonists. Median
HAS
‐
BLED
score was 2 (range, 1 to 5). Successful device implantation was achieved with a median number of 1.5 devices (median diameter 24 mm [25th to 75th percentiles: 24 to 24 mm]). Total procedure time was 97 minutes (25th to 75th percentiles: 75 to 115 minutes). At 60 days, all patients met the criteria for successful sealing. Follow‐up visit at 12 months showed a 30% rate of documented recurrence of
AF
. A repeated pulmonary vein isolation was performed successfully in 4 patients, without interference of the
LAA
closure device. No thromboembolic events occurred during 1‐year follow‐up.

Conclusion

LAA
occlusion with the Watchman device and
AF
ablation can be combined successfully and safely in a single procedure. The Watchman does not interfere with a repeated ablation.
Secreted Wnt Modulators in Symptomatic Aortic Stenosis
Authors: Askevold Erik Tandberg , Gullestad Lars , Aakhus Svend , Ranheim Trine , Tønnessen Theis , Solberg Ole G. , Aukrust Pål , Ueland Thor 
Published: May 2013

Background

Valve calcification and inflammation play key roles in the development of aortic stenosis (
AS
). The
W
nt pathways have been linked to inflammation, bone metabolism, angiogenesis, and heart valve formation. We hypothesized that soluble
W
nt modulators may be dysregulated in symptomatic
AS
.

Methods and Results

We measured circulating levels (n=136) and aortic valve tissue expression (n=16) of the secreted
W
nt modulators secreted frizzled related protein‐3, dickkopf‐1 (
DKK‐1
), and
W
nt inhibitory factor‐1 (
WIF‐1
) by enzyme immunoassay, immunostaining, and
RT‐PCR
in patients with symptomatic, severe
AS
and investigated associations with echocardiographic parameters of
AS
and cardiac function. Finally, we assessed the prognostic value of these
W
nt modulators in relation to all‐cause mortality (n=35) during long‐term follow‐up (median 4.6 years; survivors, 4.8 years; nonsurvivors, 1.9 years) in these patients. Our main findings were: (1) serum levels of all
W
nt modulators were markedly elevated in patients with symptomatic
AS
(mean increase 231% to 278%,
P
<0.001), (2) all
W
nt modulators were present in calcified aortic valves but correlated poorly with systemic levels or degree of
AS
, (3) some modulators (ie,
WIF‐1
) were associated with the degree of myocardial function and valvular calcification, (4) all
W
nt modulators, and
DKK‐1
in particular, predicted long‐term mortality in these patients also after adjusting for conventional predictors including
NT
‐pro
BNP
.

Conclusions

Together, these in vivo data support the involvement of
W
nt signaling in the development of
AS
and suggest that circulating
W
nt modulators should be further investigated as risk markers in larger
AS
populations, including patients with asymptomatic disease.
Inhibition of Apoptosis Signal–Regulating Kinase 1 Reduces Myocardial Ischemia–Reperfusion Injury in the Mouse
Authors: Toldo Stefano , Breckenridge David G. , Mezzaroma Eleonora , Van Tassell Benjamin W. , Shryock John , Kannan Harsha , Phan Dillon , Budas Grant , Farkas Daniela , Lesnefsky Edward , Voelkel Norbert , Abbate Antonio 
Published: May 2013

Background
Despite the clear advantages of reperfusion in acute myocardial infarction, part of the myocardium is injured during reperfusion by reactive oxygen species. Reactive oxygen species activate apoptosis signal–regulating kinase‐1, a key mediator in cell death. We hypothesized that inhibition of apoptosis signal–regulating kinase‐1 at the time of reperfusion would protect the heart from ischemia–reperfusion injury.

Methods and Results

Male
CD
1 mice underwent transient coronary artery ligation (30 minutes) followed by reperfusion or underwent sham surgery (n=10 to 12 per group). A selective small‐molecule inhibitor of apoptosis signal–regulating kinase‐1 (GS‐459679) was given immediately after reperfusion (10 or 30 mg/kg IP). Infarct size was measured early (at 24 hours, in a subgroup of mice) by triphenyl tetrazolium chloride staining and late (at 7 days) by
M
asson's trichrome staining for fibrosis. Apoptosis was assessed by measurement of caspase‐3 activity and by determination of
DNA
fragmentation in cardiomyocytes bordering the infarct. Transthoracic echocardiography was performed before surgery and then at 24 hours and 7 days later. Treatment with GS‐459679 at reperfusion led to a significant dose‐related reduction in infarct size (31% for 10 mg/kg [
P
<0.001 versus vehicle] and 60% for 30 mg/kg [
P
<0.001 versus vehicle]), inhibition of apoptotic cell death, and preservation of left ventricular dimension and systolic function at both 24 hours and 7 days.

Conclusions
Inhibition of apoptosis signal–regulating kinase‐1 at the time of reperfusion limits infarct size and preserves left ventricular function in a model of acute myocardial infarction in the mouse.
Resting Heart Rate and the Risk of Microvascular Complications in Patients With Type 2 Diabetes Mellitus
Authors: Hillis Graham S. , Hata Jun , Woodward Mark , Perkovic Vlado , Arima Hisatomi , Chow Clara K. , Zoungas Sophia , Patel Anushka , Poulter Neil R. , Mancia Giuseppe , Williams Bryan , Chalmers John 
Published: May 2013

Background
A higher resting heart rate is associated with an increased probability of cardiovascular complications and premature death in patients with type 2 diabetes mellitus. The impact of heart rate on the risk of developing microvascular complications, such as diabetic retinopathy and nephropathy, is, however, unknown. The present study tests the hypothesis that a higher resting heart rate is associated with an increased incidence and a greater progression of microvascular complications in patients with type 2 diabetes mellitus.

Methods and Results

The relation between baseline resting heart rate and the development of a major microvascular event was examined in 11 140 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study. Major microvascular events were defined as a composite of new or worsening nephropathy or new or worsening retinopathy. Patients with a higher baseline heart rate were at increased risk of a new major microvascular complication during follow‐up (adjusted hazard ratio: 1.13 per 10 beats per minute; 95% confidence interval: 1.07–1.20;
P
<0.001). The excess hazard was evident for both nephropathy (adjusted hazard ratio: 1.16 per 10 beats per minute; 95% confidence interval: 1.08–1.25) and retinopathy (adjusted hazard ratio: 1.11 per 10 beats per minute; 95% confidence interval: 1.02–1.21).

Conclusion
Patients with type 2 diabetes mellitus who have a higher resting heart rate experience a greater incidence of new‐onset or progressive nephropathy and retinopathy.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00145925.
http://www.advance-trial.com/static/html/prehome/prehome.asp