bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 153: High Ambient Temperature During Pregnancy Predicts Vascular Disease in the Offspring as Adult
Authors: Teji Jagjit S , Eldeirawi Kamal 
Published: March 2022

Introduction and Purpose
It well known that being small at birth is a risk factor for hypertension and obesity and diabetes related disorders of adulthood. Animal studies have demonstrated retarded placental and fetal growth when exposed to higher temperature during pregnancy.

Purpose of this study
Is high ambient temperature during pregnancy associated with low birthweight, LBW.

Methods
The data from vital statistics of birth certificates in USA 1995 through 2002. Analyzed only full term babies. Weather data from (NOAA) website; Logistical regression was performed with LBW as the dependent variable with all the other dichotomized variables gender, race, plurality, maternal education, maternal age as confounding and where independent variables latitude and/or temperature with respect to race using STATA 9.0 SE.

Results
About 25 million records from over 32 million births were used for analysis. It was noted that average annual temperature>55 F and lower latitude in the USA had a higher probability of LBW; Odds ratio (OR) 1.228029, P<0.0005; 95% CL-1.22-1.23).[Figure]. Greatest impact of LBW was for non-hispanic white, NHW and lowest for, hispanic, H, OR 1.22 vs. 1.003. Other variables had no impact on the probability of LBW when inversely related to temperature and/or lower latitude of birth.

Conclusions
1. LBW at birth is directly associated to higher environmental temperature during pregnancy. 2. Increased incidence of chronic diseases later in life, such as diabetes, obesity, and cardiovascular are associated with LBW.
Abstract 156: Statins are Effective in Lowering LDL-C in High-Risk Patients with Mitochondrial Disease
Authors: Hannah-Shmouni Fady , Sirrs Sandra , Mattman Andre 
Published: March 2022

Background
Mitochondrial dysfunction affects multiple organs with varying severity and can be either primary or secondary to other diseases (e.g.: Alzheimer’s disease) or medications. Statins may be beneficial in patients with mitochondrial disease (mitoD) who have a higher prevalence of cardiac risk factors including diabetes and sedentary lifestyle. Therefore, it would be useful to know if statins are effective in patients with mitoD for prevention of cardiovascular disease.

Methods
We identified adult patients with confirmed mitoD in our clinic. Clinical and laboratory parameters were compared between the statin and non-statin groups.

Results
56 patients had confirmed mitoD, 8 of which were on statins (average of 2 year, equivalent 20 mg daily atorvastatin) for secondary prevention. The statin group had a higher risk of cardiovascular disease (5 High, 3 Moderate Framingham risk score), including higher age (mean, years = 67 (SD 15) vs. 53 (SD 15), p<0.05) and comorbidities, such as coronary heart disease (50 vs. 15%, p<0.019), obesity (33 vs. 2%, p<0.008), diabetes mellitus (38 vs. 15%, p<0.11) and hypertension (50 vs. 40%, p<0.58). At two years, the mean reduction in LDL-C was 39.8% (SD 17%, measured in 7/8). None had myopathy with an elevated CK more than x10 the upper limit of normal (ULN), or AST more than x3 ULN, either at baseline or after the initiation of statins.

Conclusion
Our study suggests that high-risk patients with mitoD may benefit from statins, if indicated for the prevention of cardiovascular disease. The fact that the lowering of LDL-C in mitoD patients was of the same magnitude as expected in the general population suggests that there is no difference in statin metabolism in these individuals.
Abstract 158: The Impact of the Mediterranean Diet on Inflammatory Markers in Men and Premenopausal Women: Do Sex Differences Exist?
Authors: Bédard Alexandra , Lamarche Benoît , Tchernof André , Corneau Louise , Dodin Sylvie , Lemieux Simone 
Published: March 2022

Introduction
Little is known about the impact of the Mediterranean diet (MedDiet) on inflammatory markers.

Objective
To investigate the effects of a 4-week controlled isoenergetic MedDiet on adiponectin and high-sensitivity C-reactive protein (hs-CRP) concentrations in premenopausal women and age-matched men.

Methods

Participants were 37 men and 32 premenopausal women aged 24-53 years with a slightly elevated plasma LDL-C (3.4-4.9 mmol/L) or total cholesterol to HDL-C ratio ≥ 5.0, i.e. individuals for whom the adoption of healthy dietary habits is recommended in
CVD
prevention. During the experimental MedDiet, all foods and drinks were provided to participants. Adiponectin and hs-CRP concentrations were measured before and after the MedDiet by ELISA. This controlled 4-week experimental MedDiet has been previously shown to improve lipid and lipoprotein profiles and blood pressure in both men and women.

Results
Adiponectin concentration decreased in response to the MedDiet (time effect, P<0.0001), with a tendency for a greater decrease in men (-17.3%, P=0.0001) than in women (-10.7%, P=0.27; sex by time interaction effect P=0.075). A higher adiponectin concentration before the MedDiet was associated with a greater decrease in response to the MedDiet (r=-0.36 and P=0.003). The MedDiet had no impact on hs-CRP concentration in both men and women (value before the MedDiet: 1.53±0.25 mg/L in men and 2.32±0.31 mg/L in women; time effect, P=0.50; time by sex interaction, P=0.36). hs-CRP concentration before the MedDiet was negatively associated with variations in hs-CRP concentrations in response to the MedDiet (r=-0.39 and P=0.002).

Conclusions

Our results suggest that short term consumption of MedDiet in isocaloric conditions, which has overall beneficial effects on traditional risk factors, leads to a decrease in adiponectin concentration, an adipokine known for its anti-inflammatory properties, and has no impact on hs-CRP concentration. This decrease in adiponectin concentration may be more
pronounced
in men than in premenopausal women. This unexpected impact of the MedDiet on adiponectin concentration, especially in men, needs further investigation.
Abstract 192: Depletion of Inflammatory Monocytes Reduces Endothelial Nitric Oxide Synthase Uncoupling and iNOS Derived Nitrosative Stress in Angiotensin II-induced Vascular Dysfunction
Authors: Hu Hanhan , Kossmann Sabine , Schwenk Melanie , Knorr Maike , Brand Moritz , Schönfelder Tanja , Karbach Susanne H , Becker Christian , Oelze Matthias , Münzel Thomas , Daiber Andreas , Wenzel Philip 
Published: March 2022

Background
Endothelial nitric oxide synthase (eNOS) uncoupling occurs in disease states of vascular dysfunction and amplifies vascular oxidative stress and loss of NO bioactivity. Inflammatory myelomonocytic cells as a major source of superoxide are critical for angiotensin-II induced vascular dysfunction; however their role in mediating eNOS uncopuling has not been defined yet.

Methods and results

Angiotensin II (1mg/kg/d, 7d) increased the number of CD11b
+
Gr-1
low
iNOS
+
monocytes and macrophages in mouse aorta (verified by flow cytometry) in paralell to increasing nox4 and heme oxygenase 1 expression (assessed by Western blot analysis) and inducing eNOS uncoupling, measured by differential NOS dependent superoxide formation in the endothelial layer and glutathionylation of eNOS. Toxin mediated ablation of macrophages in LysM
iDTR
transgenic mice restored all of these parameters. Conversely, ablation of LysM
+
cells reduced iNOS expression and normalized vascular levels of tetrahydrobiopterin (measured by high-performance liquid chromatography) and expression of the GTP cyclohydrolase-1, essential for tetrahydrobiopterin synthesis, all of which were increased by angiotensin II in control mice.

Conclusion

Depletion of LysM
+
monocytes reduces angiotensin II induced eNOS uncopuling in vascular dysfunction, and simultaneously protects from iNOS mediated nitrosative stress: These findings highlight the role of vascular inflammatory cells in disturbed NO-bioactivity and vascular function
Abstract 227: Adipose Stromal Vascular Fraction (SVF) Vasculogenesis Demonstrates a Dose Response Through the Assembly of Endothelial Networks
Authors: Maijub John G , Boyd Nolan L , Hoying James B , Williams Stuart K , Morris Marvin E 
Published: March 2022

Objective
Critical limb ischemia (CLI) is a challenging clinical entity complicated by chronic microvascular disease. Stromal vascular fraction (SVF), a heterogeneous population of cells derived from adipose tissue, has garnered interest as a means of an autologous cell-based approach to vasculogenesis in these patients. The SVF concentration needed to achieve this goal is still unknown. Our goal was to determine if SVF vasculogenesis exhibits a dose-response using in vitro and murine in vivo models.

Methods
SVF was isolated from adult male Sprague Dawley transgenic-GFP+ Rat epididymal fat pads and serially diluted using SVF growth media and then added to a respectively labeled matrigel-coated plates. Wells were then labeled with Griffonia simplicifolia-1 (GS-1) rhodamine lectin. Phase and fluorescent microscopy images of each well were then taken. The same SVF concentrations were suspended in collagen gels and subcutaneously implanted into the flanks of 6 Rag-1 deficient mice and imaged with confocal microscopy 2 weeks later to determine if a dose-response could be seen in-vivo. Tubule length was calculated using Metamorph software.

Results

Vasculogenic networks showed monolayering at concentrations of 5.0 x 10
5
and 1.0 x 10
6
cells/mL, where as the intermediate dose exhibited greater complexity to its network. Total tubule length, measured in μm, peaked with the 2.50 x 10
5
cells/mL concentration. Tubule length increased significantly up to this peak, and then gradually decreased at higher concentrations. GS-1 staining was positive when viewing the tubules under fluorescence microscopy. Preliminary results from the in-vivo model showed increasing vasculogenesis up to a maximal tubule length for the 1 x 10
6
cells/mL concentration.

Conclusion

SVF vasculogenesis exhibits a dose-response. Tubule formation is of endothelial phenotype and tubule length is directly proportional to cell concentration up to a peak concentration of 2.5 x 10
5
cells/mL. Preliminary in-vivo data also suggests that a dose-reponse exists. We are encouraged by these results that suggest that cell based therapy may be tailored for appropriate dosing in CLI patients.
Abstract 232: Delayed Inhaled Carbon Monoxide Improves Diabetic Wound Healing
Authors: Washington Christopher B , Shukla Ankur S , Madigan Michael C , Tzeng Edith 
Published: March 2022

Background
Nonhealing wounds are a major source of morbidity in diabetic patients. These wounds persist due to a persistent inflammatory state and poor resistance to infection. Carbon monoxide (CO) is a naturally occurring byproduct of heme degradation that possesses both anti-inflammatory and pro-angiogenic properties. Thus, we hypothesize that inhaled CO will improve cutaneous wound healing in the setting of diabetes.

Methods
Excisional wounds (1.5 x 1.5 cm) were created in db/db mice. The mice were treated with inhaled CO at 250 ppm for 1 hr daily starting immediately after wounding or starting on day 8. Control mice remained in room air. Wounds were measured by planimetry. At day 20, mice were sacrificed and the residual wounds were collected for immunohistochemistry.

Results
Inhaled CO initiated immediately after wounding did not improve healing with less granulation tissue formation. However, when CO treatment was delayed until day 8, wound healing was greatly improved compared to controls (residual wounds measuring 27.2 ± 5.3% of original vs 52.2 ± 5.8% on day 20; N=10-14 per group; p < 0.005). CD31 staining showed increased angiogenesis in the delayed CO treated animals (Figure 1).

Conclusions
Early inhaled CO was detrimental to wound healing while delaying CO treatment accelerated healing, potentially through increased angiogenesis. Early administration of CO likely inhibits inflammatory responses and cellular recruitment essential for wound healing. Delayed CO may inhibit the persistent inflammation that leads to chronic non-healing wounds, allowing for improved wound healing in diabetes.
Abstract 285: The Effects of Hypercholesterolemia and Lipoprotein-Cholesterol Concentrations on Angiotensin II-Induced Abdominal Aortic Aneurysms
Authors: Liu Jing , Lu Hong , Howatt Deborah , Balakrishnan Anju , Cassis Lisa , Daugherty Alan 
Published: March 2022

Background and objective
Angiotensin II (AngII) infusion promotes abdominal aortic aneurysms (AAA) in both normo- and hypercholesterolemic mice, but the latter have a greater susceptibility, implicating a role of hypercholesterolemia in AngII-induced AAA. A recent publication demonstrated that high-density lipoprotein (HDL) administration prevented AngII-induced AAA in apoE -/- mice without affecting total plasma cholesterol concentrations. The purpose of this study was to determine the relationship between concentrations and characteristics of plasma cholesterol and lipoproteins and AngII-induced AAA.

Methods and Results
Three strains of male mice were studied: C57BL/6, LDL receptor -/-, and apoE -/-. These mice were fed either a normal diet or a saturated fat- enriched diet. AngII (1 μg/kg/min) was infused for 4 weeks through osmotic minipumps implanted subcutaneously. Total plasma cholesterol concentrations were measured using an enzymatic kit. Lipoproteins were resolved by size exclusion gel chromatography and non-HDL and HDL analyzed using Peakfit software. AAA was quantified by measuring maximal outer width of suprarenal aortas. In C57BL/6 mice, the fat-enriched diet modestly increased concentrations of total plasma cholesterol (114 ± 4 vs 99 ± 6 mg/dl; P=0.03) and HDL-C (98 ± 4 vs 81 ± 7 mg/dl; P=0.02), while did not change non-HDL-C/HDL-C ratio (0.21 ± 0.03 vs 0.24 ± 0.03; P=0.5) and AAA (1.1 ± 0.1 vs 1.1 ± 0.1 mm; P=0.6). In LDL receptor -/- mice, the fat-enriched diet feeding increased concentrations of total plasma cholesterol (1590 ± 58 vs 276 ± 9 mg/dl; P< 0.001), HDL-C (132 ± 5 vs 90 ± 3 mg/dl; P<0.001), non-HDL-C/HDL-C ratio (10.8 ± 0.3 vs 2.1 ± 0.1; P<0.001), and AAA (1.6 ± 0.1 vs 1.2 ± 0.1 mm; P=0.002), compared to LDL receptor -/- mice fed the normal diet. In apoE -/- mice, the fat-enriched diet increased concentrations of total plasma cholesterol (1261 ± 121 vs 348 ± 38 mg/dl; P<0.001), had no effect on HDL-C, increased non-HDL-C/HDL-C ratio (53.1 ± 5.9 vs 10.5 ± 2.0; P=0.016), and had no effect on AAA development (1.5 ± 0.2 vs 1.6 ± 0.2 mm; P=0.4).

Conclusion
Hypercholesterolemia promotes AngII-induced AAA, while AAA has no clear relationship with either concentrations of total plasma cholesterol or HDL-C.
Abstract 287: Oxidative Stress Modulates Vascular Smooth Muscle Cell Phenotype via Connective Tissue Growth Factor in Thoracic Aortic Aneurysm
Authors: Branchetti Emanuela , Poggio Paolo , Sainger Rachana , Shang Eric , Grau Juan B , Jackson Benjamin M , Lai Eric , Parmacek Michael S , Gorman Robert C , Gorman Joseph H , Bavaria Joseph E , Ferrari Giovanni 
Published: March 2022

Rationale.
Thoracic Aortic Aneurysm (TAA) is characterized by a dysregulation of cellular and extracellular components of the aortic wall which contribute to the weakening of the ascending aorta. Oxidative stress has long been implicated in the pathogenesis of aneurysms for its role in inducing cellular apoptosis and matrix degradation. However, the link between oxidative stress and TAA formation remains to be firmly established. Connective Tissue Growth Factor (CTGF) regulates matrix biosynthesis as well as Vascular Smooth Muscle Cells (VSMC) proliferation and apoptosis. We hypothesized that Reactive Oxygen Species (ROS), modulated by altered hemodynamic conditions, could regulate VSMC phenotype and matrix composition via CTGF, affecting - in turn - the aortic tissue structure.

Methods.
Finite element analysis (FEA) based on computed tomography geometries was used to estimate wall stress in control and TAA patients. In vitro and ex vivo studies on human tissues and isolated VSMC were used to demonstrate the correlation between ROS, CTGF, and VSMC synthetic phenotype in TAA development. Results were validated in vivo by a murine model of TAA based on Angiotensin II (AngII) infusion.

Results.
TAA patients have higher wall stress in the ascending aorta than non-dilated patients. High aortic wall stress is associated with increased levels of ROS, media degeneration and accumulation of synthetic VSMCs in TAA tissues. ROS directly induce CTGF expression, which modulates synthetic VSMC phenotype in human isolated cells. ROS effect is reverted in vitro either using a neutralizing antibody against CTGF or by antioxidant administration. In AngII- induced TAA in mice, medial thickening and luminal expansion of the proximal aorta are associated with ROS accumulation, CTGF up-regulation and VSMC with a synthetic phenotype as seen in human specimens.

Conclusions.
Increased peak wall stress correlates with change in VSMCs towards a synthetic phenotype mediated by ROS accumulation via CTGF. Understanding the molecular mechanisms that regulate VSMCs towards a synthetic phenotype could unveil new regulatory pathways for aortic homeostasis and identify new therapeutic targets for patients at risk of aortic dissection and rupture.
Abstract 298: Microfibrillar Protein 4 is an Integrin avß3/5 Ligand Involved in Vascular Remodeling
Authors: Schlosser Anders , Lindholt Jes S , Kejling Karin , Kristmannsdottir Gudlaug B , Pilecki Bartosz , Wulf-Johansson Helle , Møller Jesper B , Füchtbauer Ernst M , Nielsen Ole , Hemstra Line E , Dubey Lalit K , Hansen Pernille B , Stubbe Jane , Ratkolb Birgit , Schrewe Anja , Bekeredjian Raffi , Wolf Eckhard , Gailus-Durner Valerie , Fuchs Helmut , Hrabê de Angelis Martin , Holmskov Uffe , Sorensen Grith L 
Published: March 2022

Arterial injury stimulates remodeling responses that, when overexuberant, leads to stenosis. This response is influenced by specific integrin signaling in vascular smooth muscle cells (VSMCs). Microfibrillar-associated protein 4 (MFAP4) is a matricellular integrin ligand localized to the vascular wall. We hypothesized that systemic MFAP4 (sMFAP4) associates to vascular remodeling processes and that MFAP4 enhances integrin dependent VSMC activation and vasculoproliferative disease-associated remodeling.
We explored the hypotheses using a prospective human cohort with symptomatic obstructive peripheral arterial disease (PAD), VSMC culture studies, and produced MFAP4 deficient mice for studying neointima formation.
We demonstrate that the highest tertile of sMFAP4 was significantly associated with primary patency after vascular reconstruction, and the overall need for vascular reconstruction and mortality in 343 PAD patients.
MFAP4 mediated the adhesion, migration, and proliferation of VSMCs in an integrin αVβ3/5-dependent manner in vitro. These effects were inhibited by MFAP4-blocking antibodies. MFAP4-deficient mice displayed delayed neointimal formation when challenged with carotid artery ligation, but the compensatory outward remodeling of vessel diameter was reduced.
In conclusion, sMFAP4 has the potential to serve as a systemic marker morbidity and mortality in PAD. MFAP4 regulates integrin αVβ3/5 signaling and pathological remodeling in vivo, and may have therapeutic implications in vasculoproliferative diseases.
Abstract 322: Azathioprine Reduces Endothelial Cell Activation via Inhibition of GTPase Rac1
Authors: Marinkovic Goran , Hoogenboezem Mark , van Buul Jaap , de Vries Carlie J , de Waard Vivian 
Published: March 2022

Objective
Azathioprine (AZA) and its active metabolite 6-mercaptopurine (6-MP) are well established immunosuppressive drugs. Common understanding of its immunosuppressive properties is largely limited to immune cells. However, 6-MP also has a potential to effectively modulate the inflammatory phenotype of endothelial cells. Activation of endothelium is a fundamental feature in chronic inflammatory diseases. We studied the mechanism underlying the protective role of the immunosuppressive drug 6-MP in endothelial cell activation.

Methods and Results
Since it is known that Aza affects small GTPase Rac1 in T-cells, we focussed on Rac1-mediated processes in cultured endothelial cells in the presence or absence of 6-MP. Indeed, upon treatment with 6-MP, we observed a decrease of GTP-bound Rac1, confirming that there is less active Rac1. Reduced activity of Rac1 influences the downstream signaling cascade, resulting in decreased phosphorylation of c-Jun terminal N-Kinase (JNK), c-Jun and thus, reduced transcription of pro-inflammatory genes. On mRNA level, in the presence of 6-MP we confirmed that endothelial cells express less proinflammatory chemokine CCL5 (Rantes), Interleukin-12 and adhesion molecule VCAM1; genes downstream of the Rac1-mediated JNK signalling pathway. In addition, monocyte adhesion to activated endothelial cells is strongly inhibited upon 6-MP treatment, Indeed, reduced cytoskeletal rearrangement is observed in the form of actin protrusions that capture leukocytes, which is a process that relies on Rac1 activation. Specifically, a 47% reduction in number of transmigratory cups is observed, resulting in a reduction of adherent Anti-ICAM-1 Ab-coated beads (monocytes substitute).

Conclusion
These data underscore the anti-inflammatory effect of 6-MP on endothelial cells, modulating the activation response of endothelial cells in a Rac1-dependent fashion and providing us with a mechanistic insight for the development of novel therapeutic targets against chronic inflammatory diseases.
Abstract 337: Measurements of Calf Muscle Oxygenation During Standing and Exercise in Patients with Chronic Venous Insufficiency
Authors: Yamaki Takashi , Konoeda Hisato , Osada Atsuyoshi , Hamahata Atsumori , Nozaki Motohiro , Sakurai Hiroyuki 
Published: March 2022

BACKGROUND
Despite the established role of the calf muscle pump for preventing chronic venous insufficiency (CVI), hemoglobin flow in the calf muscle is poorly understood. Near-infrared spectroscopy (NIRS) provides continuous noninvasive monitoring of changes in tissue oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) levels. The purpose of this study was to investigate the changes in calf muscle HbO2 and HHb levels during standing and exercise in patients with CVI.

METHODS
Seventy-four limbs in 73 patients with various clinical stages of CVI were enrolled. Patients were divided into early (C0-C3) and advanced (C4a-C6) according to the CEAP classification. NIRS was used to measure changes in the calf muscle HbO2 and HHb levels, and oxygenation index (HbD; HbD=O2Hb-HHb) while lying spine, standing, and then subsequently performing 10 tiptoe movements.

RESULTS
Among the 74 limbs evaluated, 47 had early and 27 had advanced CVI. Standing caused increases in both O2Hb and HHb levels. However, there were no significant differences in these increases, or HbD, between early and advanced CVI. In contrast, the time elapsed until the maximum increase in O2Hb concentration was significantly reduced in patients with advanced CVI in comparison with patients showing early CVI (55.5 ± 44.2, 32.6 ± 12.6 s, P=.025). During 10 tiptoe movements, a decrease in O2Hb concentration was observed, and there was no significant difference in the reduction of O2Hb values between early and advanced CVI. In contrast, 10 tiptoe movements produced venous emptying (HHbE) and subsequent retention (HHbR), and the HHbR was significantly increased in patients with advanced CVI compared with those with early CVI (6.0 ± 7.0, 9.0 ± 6.2 μmol/L, P=0.021). Furthermore, HbD falls were more pronounced in patients with advanced CVI (7.4 ± 11.5, -5.9 ± 15.7 μmol/L, P=0.002).

CONCLUSIONS
Changes in O2Hb and HHb concentrations differ between early and advanced CVI during standing and exercise. Detailed investigation of the interrelationship between O2Hb and HHb during calf muscle pump function would lead to a better understanding of the various clinical stages of CVI.