bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 355: β-Adrenergic Stimulation Impact on Cerebrovascular Contractility Through Actin Cytoskeleton Disorganization in Rabbits
Authors: Kim Nari , Kim Hyoung Kyu , Heo Hye-Jin , Ko Kyung Soo , Rhee Byoung Doo , Han Jin 
Published: July 2021

Beta-adrenoceptor stimulations have been well-known to initiate cardiac hypertrophy accompanied by extracellular remodeling that predisposes heart failure and cardiac dysarrhythmia. However, less is known concerning cerebrovascular dysfunction induced by beta-adrenergic stimulation. We investigated whether cerebrovascular functions and related biochemical signal pathways were altered during beta-adrenergic stimulations in rabbits.
New Zealand white rabbits have been injected with isoproterenol (ISO, 0.3 mg/kg/day) for 7 days. We have studied the alteration of protein expression in cerebral arteries (CAs) using 2DE proteomics and western blot analysis and further analyzed those data using bioinformatics software. Reactive oxygen species generation and followed DNA damage were assessed deteriorative effect of ISO on CAs. Vasocontractility response to angiotensin II (Ang II) and related biochemical signal pathways were assessed to evaluate functional alteration of CAs.

Proteomic analysis revealed remarkably decreased expression of cytoskeleton organizing proteins, (e.g. actin related protein 1A and 2, α-actin, capping protein Z beta, and vimentin) and anti-oxidative stress proteins (e.g. heat shock protein 9A and stress-induced-phosphoprotein 1) in ISO-stimulated CAs. As a cause of dysregulation of actin cytoskeleton organization, we found decreased level of RhoA/ROCK1, major regulators of actin cytoskeleton organization. As functional consequences of proteomic alteration, we found the decreased transient Ca
2+
efflux and contraction response to Ang II and high K
+
in ISO-stimulated CAs.

We suggested that ISO stimulations reduced RhoA/ROCK activities and modified key actin based cytoskeletal and antioxidative proteins in CAs, which consequently lead to impair cerebrovascular contractility response to Ang II in rabbits.
Abstract 127: The Mediterranean Diet With and Without Weight Loss Improves Several Features of Low-Density Lipoprotein Metabolism in Men With Metabolic Syndrome
Authors: Richard Caroline , Couture Patrick , Desroches Sophie , Lamarche Benoît 
Published: July 2021

Objective
To assess the impact of a Mediterranean type diet (MedDiet), without weight loss (-WL) and with weight loss (+WL), on features of LDL and LDL- apolipoprotein (apo) B metabolism in men with metabolic syndrome (MetS).

Methods and Results
The diet of 19 men with MetS (NCEP-ATP III, age 24-62 years) was first standardized to a typical North American control diet that they consumed for 5 weeks under isoenergetic feeding conditions (all foods and beverages provided). Subjects were then fed a MedDiet for 5 weeks also under isoenergetic conditions (MedDiet-WL), after which they underwent a 20-week weight loss period in free-living conditions (average weight loss -10.2 ± 2.9% body weight, P<0.01). This was followed by consumption of the MedDiet (5 weeks) under isoenergetic conditions (MedDiet+WL). Features of LDL and apo B kinetics were assessed at the end of the three controlled feeding periods. MedDiet-WL reduced VLDL-apoCIII (-41.5%), cholesteryl ester transfer protein (-7.0%) and hepatic lipase concentrations (-7.1%), reduced the proportion of small LDL (LDL<255 å, -11.7%) and increased LDL peak particle diameter (LDL-PPD, +0.7%) as well as the proportion of medium size LDL (LDL255-260 å, +11.1%) vs. control diet (all P<0.05). MedDiet-WL also decreased LDL-apoB pool size (PS, -14.2%) and increased the fractional catabolic rate (FCR) of LDL-apoB (+30.4%) vs. the control diet (both P<0.05), with no change in LDL-apoB production rate (PR). MedDiet+WL was associated with further increase in LDL-PPD (0.2%) and further reduction in VLDL-apoCIII concentrations (-28.7%) compared with MedDiet-WL (both P<0.05) but had no further impact on LDL-apoB PS and on LDL-apoB FCR.

Conclusion
Data from this controlled feeding study suggest that consumption of MedDiet, even in the absence of weight loss, decreases LDL-C concentrations and LDL-apoB pool size primarily by enhancing the clearance of LDL particles in men with MetS. This is accompanied by a reduction in the proportion of small dense LDL and an increase in LDL particle size. Combining weight loss to MedDiet has no additional impact on LDL-apoB pool size and catabolism but may have further beneficial effects on the LDL particle size phenotype in men with MetS.
Abstract 163: The Prevalence of the Metabolically Healthy Obese Phenotype in an Aging Population and its Association with Subclinical Cardiovascular Disease: The Brazilian Study on Healthy Aging
Authors: Roberson Lara L , Siddiqui Shozab A , Blaha Michael J , Agatston Arthur A , Blumenthal Roger S , Santos Raul D , Nasir Khurram , Sposito Andrei C 
Published: July 2021

BACKGROUND
Obese and overweight individuals have been shown to be at higher risk of CVD events than normal weight individuals. Current literature has elucidated a new phenotype, Metabolically Healthy Obese (MHO), with risks of CVD similar to that of normal weight individuals. Few studies have examined the MHO phenotype in an aging population, especially in association with subclinical cardiovascular disease.

METHODS
The cross sectional study population consisted of 208 individuals (79% Female), age 80 and older (mean age 84±4, range 80-102). Anthropometrics & biochemical parameters were measured. The Adult Treatment Panel definition of metabolic syndrome (MetS), excluding waist circumference, criteria was used to define metabolically healthy (<3 MetS components) versus unhealthy. A combination of BMI and waist circumference were used to define normal weight and overweight/obese. Multidetector-row cardiac CT for coronary artery calcium score (CACS) was used to detect subclinical atherosclerosis. High reactive C reactive protein (hs-CRP) was measured to assess degree of underlying inflammation.

RESULTS
The prevalence of MHO defined by BMI≥25 kg/m2 &/or waist circumference >88cm in women, >102cm in men & having 3mg/dl, Uric Acid >6 mg/dl (p=NS). Gender, total cholesterol, HDL, LDL, triglycerides, and SBP was significantly associated with MHO (p<0.05).

CONCLUSIONS
Our results suggest that the MHO phenotype is still seen in octogenarians, but at lower rates than in the general population suggesting MHO may not simply be an intermediary stage, driven by length of spent in the obese state. Those with this phenotype tended to have lower triglycerides, higher HDL, and lower body fat % than their metabolically at risk obese counterparts (p<0.05), however, degree of subclinical CVD was not different. Further studies are needed to explore the related risk of CVD among MHO octogenarians.
Abstract 251: Effects of n-3 Fatty Acids Supplementation on Endothelial Function and Inflammation in Peripheral Artery Disease: The OMEGA-PAD Trial
Authors: Grenon Marlene , Owens Christopher , Alley Hugh , Chong Karen , Yen Priscilla , Vittinghoff Eric , Harris William , Hughes-Fulford Millie , Rapp Joseph , Conte Michael 
Published: July 2021

Background
Patients with peripheral artery disease (PAD) have an increased risk for cardiovascular events, likely related to inflammation and impaired endothelial function. n-3 polyunsaturated fatty acids (n3-PUFAs) have been shown to improve endothelial function and reduce inflammation in other cohorts. We hypothesized that n3-PUFAs would improve endothelial function and the inflammatory profile in patients with PAD.

Methods

This is a randomized, double-blind, placebo-controlled trial: the OMEGA-PAD trial (
NCT01310270
). Eighty patients aged 50 and more with intermitted claudication and an ankle-brachial index (ABI) of <0.9 presenting to vascular surgery clinic at the Veterans Affairs Medical Center in San Francisco will be randomized to n3-PUFAs 2.2 g orally twice daily (total of 4.4gm/day) or a matched placebo for 1 month. Outcome measurements are done at baseline and after 1 month. The primary endpoint is a change in endothelial function measured by brachial artery flow mediated, endothelium-dependent vasodilation (FMD). Secondary endpoints include a change in inflammatory markers (C-reactive protein, IL-6, sICAM-1 and TNF-α), improvement in lipid profile (LDL, triglycerides, HDL), blood pressure and walking distance by questionnaire. The omega-3 index will be measured to ensure physiological treatment effect.

Results
Recruitment for the OMEGA-PAD trial started in April 2011. Fifty male veterans have been enrolled and randomized. The mean age is 67 ± 9 years. Mean index limb ABI is 0.8 ± 0.2. CAD is present in 36%, hypertension in 92%, and diabetes mellitus in 32%. 47% are current smokers and 45% are former smokers. Mean HgA1c is 8±1, LDL 93±37 mg/dL, triglycerides 160±98 mg/dL and HDL 43 ±12 mg/dL. Baseline brachial FMD is 7±4% indicating an overall impairment of endothelial function in this cohort. The inflammatory burden of this cohort is substantial as evidenced by hsCRP 5±5 mg/L. The baseline omega-3 index is 5±2%.

Conclusions
The OMEGA-PAD trial will test the novel hypothesis that n3-PUFAs supplementation improves functional and inflammatory parameters in a cohort at high vascular risk. The results of this study will provide valuable mechanistic insight into PUFAs as well as inform on this class of agents for cardiovascular outcome trials.
Abstract 255: Cytoprotective Effects of Erythropoietin and Erythropoietin-derivatives in Ischaemic Human Myotubes and the Role of Pi3k/akt Signalling Pathway
Authors: Yu Rebekah Sian Hwee , Baker Daryll , Abraham David , Tsui Janice 
Published: July 2021

Objectives
Erythropoietin (Epo) has tissue-protective effects in response to injury, acting through the EpoR-βcR heteroreceptor. We have previously demonstrated the presence and interaction of the EpoR and βcR in human skeletal muscle. Here we aim to investigate the potential cytoprotective effects of Epo and an Epo-derivative (ARA-290) in a human in vitro model of skeletal muscle and establish a potential downstream signalling pathway utilised in protecting cells from apoptosis (including Jak-2, PI3k/Akt, NFkB).

Methods
Gastrocnemius muscle biopsies were obtained from patients with critical limb ischaemia and control samples were obtained from non-ischaemic patients. Human myoblasts were isolated from muscle biopsies, cultured, and allowed to differentiate into myotubes in order to investigate the cytoprotective effects of Epo and ARA-290 on myotubes subjected to simulated ischaemia. The PI3k inhibitors, LY294002 and wortmannin, were then used to determine the role of PI3k/Akt pathway in mediating cytoprotection. Following this, inhibitors against the upstreatm (Jak-2) and downstream (NFkB) molecules were also investigated. Western blot analysis, using the pro-apoptotic marker cleaved caspase-3 was performed and compared with levels of Akt and phosphorylated-Akt, using western blot analysis.

Results
Exogenous administration of Epo and ARA-290 were able to ameliorate the ischaemia-induced apoptosis on isolated human myotubes as shown by a significant reduction in cleaved caspase-3 expression. Addition of all inhibitors, to ARA-290 or Epo pre-treated cells, abolished the reduction in apoptosis.

Conclusion
The ability of ARA-290 to attenuate apoptosis in human myotubes undergoing ischaemic insult suggests a potential role in tissue protection in skeletal muscle injury. We propose that the PI3k/Akt signalling pathway is involved in mediating this cytoprotection.
Abstract 266: The Usefulness of a Collagen Plug Vascular Closure Device in Patients Undergoing Coronary and Peripheral Percutaneous Intervention
Authors: Owens John T , Tordini Andrea , Bhatty Shaun , Danyi Peter , Patel Kalpesh , Jovin Ion S 
Published: July 2021

Background
Vascular access site complications can follow coronary and peripheral angioplasty procedures and be associated with significant morbidity. We compared the complication rates of the Angioseal closure device with complication rates after manual compression in patients undergoing coronary and peripheral interventional procedures.

Methods and Results
We studied 553 predominantly male patients undergoing percutaneous coronary, peripheral interventions, FFR or IVUS at a Veterans Administration Medical Center. The mean age was 64.6 years. Angioseal closure devices were used in 388 (70%) patients and manual compression was used in 165 (30%) patients. Major groin complications such as arteriovenous fistula, pseudoaneurysm or hematoma greater than 5 cm occurred in 16 (4.16%) patients who had an Angioseal closure device and 11 (6.67%) patients in whom manual compression was used for hemostasis (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.29-1.40; P=0.26). Other complications such as minor bleeding requiring additional manual compression, bruising, pain and swelling occurred in 32 (8.42%) patients who had an Angioseal closure device and 21 (12.4%) patients who had manual compression (OR 0.65, 95% CI 0.36-1.17; P=0.15). After adjustment for other comorbid factors such as age, type of anticoagulant used, peripheral vascular disease and chronic kidney disease, the association of major complications with the use of the Angioseal closure device remained similar to manual compression (OR 0.75, 95% CI 0.28-1.91; P=0.49). However, there was a trend for fewer minor complications with the closure device (OR 0.57, 95% CI 0.26-1.08; P=0.08).

Conclusion
In this cohort of predominantly male patients undergoing percutaneous coronary and peripheral intervention, the use of the Angioseal closure device was not associated with a decreased risk of major groin complications, but was associated with a trend for a decreased risk of minor complications compared to manual compression.
Abstract 269: Development of Acute Heart Failure Following Cardiac Catheterization in Patient’s With Pre-Existing Peripheral Artery Disease
Authors: Harris Gregory , Patwardhan Manish , Cameron Yara , Adusumalli Sundeep , Daggubati Ramesh 
Published: July 2021

Background
Peripheral artery disease has long been considered a CHD risk equivalent resulting in increased CAD, angina, CHF, and MI. Regardless, it is not known if PAD results in increased likelihood of acute complications following cardiac catheterization.

Methods
The medical records of 3817 patients undergoing cardiac catheterization at a university medical center were reviewed. Development of acute heart failure 72 hours after the procedure was compared to pre-existing medical conditions including peripheral artery disease using multiple logistic regression analysis. Results in the table below are reported as odds ratios with 95% confidence interval. Chi-square was measured comparing PAD with post procedure heart failure. Relative risk reported with 95% confidence interval.

Results

As shown below, there was a statistically significant difference between development of acute heart failure up to 72 hours after cardiac catheterization in patients with pre-existing PAD as well as history of hyperlipidemia. Chi-square demonstrated 22% of patients who developed heart failure also had pre-existing PAD (χ
2
(1,N=3816)=6.336,
p
=0.012). Relative risk of developing heart failure with pre-existing PAD was 1.782 (95% CI 1.13-2.80).

Conclusion
We have demonstrated in this retrospective analysis of 3817 patients, an increased risk of developing heart failure in patients with pre-existing PAD and dyslipidemia following cardiac catheterization. These results further justify optimal lipid management as an integral component of cardiovascular health, not only in relation to chronic disease, but also in the presence of acute injury.

Legend
PAD = Peripheral Artery Disease
Abstract 277: Downregulation of PDGF-D is Associated with Increased Collagen Production in Abdominal Aortic Aneurysm
Authors: Vorkapic Emina , Mäyränpää Mikko , Roy Joy , Eriksson Per , Wågsäter Dick 
Published: July 2021

BACKGROUND
Abdominal aortic aneurysm (AAA) is characterized by loss of aortic smooth muscle cells (aoSMCs) and remodeling of extracellular matrix, such as collagen. Platelet-derived growth factor-D (PDGF-D) is the latest discovered member of the PDGF/VEGF family and involved in proliferation and migration of SMCs. Here we analyzed the expression of PDGF-D in human and murine AAA. Furthermore, we studied the potential role of PDGF-D in regulation of collagen in cultured aoSMC.

METHOD AND RESULTS

Gene expression analysis of abdominal aortas revealed a significant lower expression of PDGF-D (-85%) and its receptor PDGFR-β (-73%) in human aneurysmal wall compared to non-aneurysmal control aortas. PDGF-D and PDGFR-β was mainly localized to SMC and endothelial cells as determined by immunohistochemical analysis and was expressed weaker in aneurysmal samples compared with controls. In mice, luminal aortic diameter was increased by 60% (P<0.001) in aortas treated with 0.5M CaCl
2
compared to saline treated control aortas. In agreement with human AAA, PDGF-D expression was significantly decreased in mice with AAA (-60%) compared to controls. A decrease in the expression of PDGF-D was strongly correlated to both α-actin (r=0.95, P<0.001) and SM22α (r=0.94, P<0.001) expression. A decreased expression of PDGF-D (r=-0.76, P<0.05) and α-actin (r=-0.88, P<0.01) was correlated with increased expression of the apoptosis marker caspase-3. To investigate the potential inhibitory role of PDGF-D in collagen remodeling, cultured aoSMCs were stimulated with 20 ng/ml of human recombinant PDGF-D or PBS as control for 24 and 48 hours. Treatment of aoSMC with rh-PDGF-D resulted in a decrease in the synthesis of collagen-III (P=0.023) and -IV (P=0.01) as well as prolyl 4-hydroxylase (P=0.01) and lysyl oxidase (P=0.02) after 48 hours. The synthesis of collagen-I was unaffected with increased PDGF-D.

CONCLUSION
Our findings imply that PDGF-D functions as a negative regulator of collagen synthesis and that lack of PDGF-D could therefore be important for the AAA process.
Abstract 312: Mapping the Inflammatory Macrophage Response during Arteriovenous Fistula Maturation by In Vivo Molecular Imaging
Authors: Cui Jie , Kessinger Chase W , McCarthy Jason R , Lin Charles , Jaffer Farouc A 
Published: July 2021

Introduction
Inflammation plays a critical role in neointimal hyperplasia (NH), which leads to arteriovenous fistula (AVF) failure in hemodialysis patients. However, the spatial distribution of macrophages in vivo post AVF creation remains unclear. In this study, we mapped the distribution of macrophages in AVF using intravital fluorescence microscopy (IVFM) and a fluorescence macrophage nanosensor, CLIO-VT680. We hypothesized that the intensity of CLIO-VT680 signals would illuminate the topography of AVF inflammation.

Methods
AVF was created in C57BL/6J mice (n=5) by end to side anastomosis between the jugular vein and the ipsilateral carotid artery. Mice were injected with CLIO-VT680 (10mg/kg) at day 13 post AVF creation and imaged by IVFM 24 hours later. AVF was resected at week 6, and Von Gieson (VVG) staining was performed. Mean CLIO signal intensity (MSI) was measured every 60μm from the anastomosis. Target to background ratios (TBRs) were calculated as the MSI of AVF divided by the MSI of the control artery. TBR ratio was calculated by the TBRs at different distance away from the anastomosis divided by the TBR at the anastomotic site.

Results
The survival rate of mice after AVF creation was 100%. The penetration depth of IVFM was 200μm. IVFM detected significantly higher TBRs of CLIO signals near the anastomotic site (p<0.05). There is a linear relationship between TBR ratios and the distance away from the anastomosis (R2=0.99). VVG staining of resected AVF showed the volume of NH decreased as the distance away from the anastomosis increased.

Conclusion
Macrophages response can be detected via CLIO-VT680 using IVFM. In vivo molecular imaging may be able to predict AVF failure.
Abstract 321: The E12/id3 Axis Regulates Ccr6 Expression In B Cells Which Are Associated With Human Atherosclerosis
Authors: Morris-Rosenfeld Sam , Perry Heather , Lipinski Michael , McSkimming Chantel , Garmey James , Taylor Angela , McNamara Coleen 
Published: July 2021

Background
Aortic homing of B cells and B cell mediated atheroprotection depend on the helix-loop-helix (HLH) transcription factor Id3. We identified that CCR6, a downstream target of Id3, is also essential for B cell homing to the aorta. Id3 functions through dominant negative inhibition of basic-HLH transcription factors such as E proteins. We have shown that a non-synonomous single nucleotide polymorphism in Id3 correlates with human carotid intimal medial thickness (cIMT). The protein encoded by this risk allele shows attenuated interaction with E12 yet whether this property is shared with other E proteins and the potential impact of Id3 and E12 on CCR6 expression in B cell subsets is unknown.

Results
Co-IPs of ancestral and polymorphic Id3 with the four known E proteins showed that E12, and not other E proteins, had significantly decreased interaction with polymorphic Id3. To address the regulatory role of Id3 on CCR6 in B cells, B cell subsetting by flow cytometry was done showing that B cell specific Id3 knockout mice (Id3fl/flApoe-/-CD19cre/+) indeed have significantly fewer CCR6 positive B cells which is in agreement with our previous findings in global Id3 knockout mice. To address the regulatory role of E12 on CCR6 expression similar subsetting of global E12 knockout mice (E12-/-Apoe-/-) was done showing they have significantly more CCR6 positive B cells of all subsets (B1a, B1b, B2) compared to wildtype. In particular the atheroprotective B1a subset had the greatest percentage increase due to loss of E12 compared to other subsets. Finally, we addressed whether CCR6 on human B cells correlates with human atherosclerosis. We found that coronary plaque burden and stenosis as measured by intravascular ultrasound (IVUS) in patients undergoing coronary catheterization correlated inversely with the average amount of CCR6 on B cells.

Conclusions
Our data suggests that Id3 is a key activator of CCR6 expression in B cells through dominant negative inhibition of E12. Furthermore, it raises the interesting possibility that CCR6 could play an important atheroprotective role through its regulation of B cell homing in humans.