bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 324: Tumor Necrosis Factor-a (TNF-a) Mediates Microvascular Dysfunction Induced by High-fat Diet and Murine Cytomegalovirus (mCMV) Infection in a Mouse Model
Authors: Khoretonenko Mikhail V , Stokes Karen Y 
Published: July 2021

Cardiovascular diseases are mediated by a variety of risk factors, e.g. obesity and infections. Complicated obesity and mCMV each induce microvascular dysfunction in mouse models. However, the impact of mild obesity on microvascular homeostasis and its possible synergism with cytomegalovirus infection remain unclear.
We have shown that 8 wks high-fat diet (HFD) increases leukocyte recruitment in cremasteric post-capillary venules, and mCMV accelerates and sustains this response. We hypothesized that HFD and/or mCMV impair phenylephrine-mediated vasoconstriction in arterioles, and that the arteriolar and venular responses are mediated by an imbalance between TNF-α and leptin, vs. adiponectin.
Mice were inoculated with mock or mCMV and at 4 wks post-infection (pi) started on HFD or left on normal diet (ND). At 12 wks pi, leukocyte recruitment and arteriolar vasoconstriction were assessed by intravital microscopy. Adiponectin and leptin were measured by ELISA. Some mice were treated with anti-TNF-α antibodies 2 days prior to observation.
mCMV infection alone did not alter any parameter when compared to Mock-ND. Arteriolar vasoconstriction to phenylephrine was impaired in both HFD groups vs. Mock-ND mice. TNF-α inhibition partially restored this impaired vasoconstriction. Leukocyte adhesion was increased in both HFD groups vs. ND mice, and was ameliorated by anti-TNF-α antibody treatment in mCMV-HFD, but not Mock-HFD mice. Adiponectin levels in HFD vs. ND groups were slightly increased, and leptin levels were ~5-6-fold higher.
Our results suggest that HFD-/+mCMV infection impairs arteriolar vasoconstriction via a TNF-α dependent mechanism. TNF-α independent HFD-induced leukocyte adhesion in venules is changed to a TNF-α dependent pathway by mCMV infection. Increased leptin levels in HFD groups correlate with previous findings linking obesity and increased leptin. Increased adiponectin levels in HFD animals are contrary to responses previously reported for complicated obesity and may represent an initial compensatory role for adiponectin in the response to HFD-induced weight gain and inflammation. However, the roles for leptin and adiponectin require future investigation.
Abstract 338: Patient with Triple Threat Survives DVT and Pulmonary Embolism Complication
Authors: Shalshin Aleksander , Mensch Alan , Kapoor Karnika 
Published: July 2021

Introduction
The risk factors for DVT and complication of PE are firmly documented in literature. Virchow’s triad describes the three most common categories responsible for venous thrombosis occurrence: Hypercoagulation, Stasis and Endothelial Injury.
Our patient was diagnosed with near fatal episode of DVT and PE as a result of all 3 risk categories in combination, based on iatrogenic and inherited causes.

Discussion
Patient presented with left leg edema and shortness of breath. He described recent arthroscopic surgery performed on left knee for meniscal tear. Listed home medications included testosterone supplement for muscle building purposes. Furthermore, patient’s family history provided vague details about possible history of blood clots on maternal side.
Patient physical examination pertinent demonstrated left lower extremity edema and tenderness on palpation.
Imaging - CT scan showed multiple PE, saddle PE and lower extremity Doppler sonogram provided evidence of DVT in left femoral and popliteal vein.
Further evaluation into hypercoagulation disorders showed that patient had an inherited condition of Protein C deficiency.

Summary
Our patient’s etiology for occurrence of DVT and PE was identified with utilization of history, physical examination, imaging and laboratory investigation.
The unique combination of iatrogenic (surgery and testosterone use) and non-iatrogenic (inherited) risk factors resulting in this patient’s clinical diagnosis are an important reminder to clinicians of all specialties to consider various elements of Virchow’s triad when approached with problem of venous thrombosis. Our patient demonstrates a classic element of each - endothelial injury (recent knee surgery), stasis (limited weight bearing post operatively), hypercoagulation (testosterone use and Protein C deficiency). Economic burden of DVT, PE remains high and is often associated with post thrombotic complications mounting economic and clinical expenditure. Timely detection, appropriate therapy and provider education about high risk population has the potential for clinical and economic benefit.
Our patient was placed on anticoagulation, counseled about testosterone use, and Protein C deficiency condition.
Abstract 380: Aging Enhances Endoplasmic Reticulum Stress-Induced Apoptosis in Murine Macrophages
Authors: Goldstein Daniel R , Song Yang 
Published: July 2021

Introduction and hypothesis
Aging enhances atherosclerosis for unclear reasons. As macrophage apoptosis and endoplasmic reticulum (ER) stress contribute to atherosclerosis, we examined if aging sensitizes these cells to apoptosis during ER stress.

Methods and Results
Peritoneal macrophages were isolated from young (aged 2-4 months) and aged (aged 16-18 months) mice, exposed to the ER stress inducer tunicamycin (TM) in vitro, and apoptosis was measured by Annexin V staining via fluorescent microscopy. We found that aged macrophages exhibited significantly more apoptosis than young macrophages (see Figure). We next measured key ER stress proteins in macrophages by Western blot to determine the underlying molecular pathways impacted by aging. With aging, we found reduced activation of inositol-requiring enzyme-1 (IRE1α), a key ER stress transducer. We next examined if augmenting activated IRE1α levels in aged macrophages reduced apoptosis during ER stress. We employed siRNA to knock down x-box binding protein 1 (XBP1), a downstream effector of IRE1α, which has been shown to induce feedback activation of IRE1α in hepatocytes. siRNA to XBP1 significantly reduced tunicamycin-induced cell apoptosis in aged macrophages from 26.1±0.408% to 5.48±1.38% (p<0.05) but not in young macrophages.

Conclusions
Our study has uncovered a novel, age-dependent interaction by which macrophages undergo apoptosis upon ER stress, and suggests that enhancing IRE1α activation will alleviate aging-augmented ER stress and subsequent apoptosis. This novel interaction may have important implications for the pathogenesis of atherosclerosis with aging.
Abstract 382: Anti-MAA Antibodies in Sprague Dawley Rats are Increased in Response to a High Fat Western Diet
Authors: Duryee Michael J , Dusad Anand , Shurmur Scott W , Johnston Michael D , Garvin Robert P , Hunter Carlos D , Anderson Daniel R , Thiele Geoffrey M 
Published: July 2021

Introduction
Malondialdehyde/Acetaldehyde (MAA) modified proteins have been suggested to play a role in the development/progression of atherosclerosis. Circulating antibodies directed against these proteins have recently been shown to be associated with the severity of the disease. More specifically, the isotype of the antibody to MAA correlated with either an acute MI (IgG) or stable plaque formation (IgA) formation. MAA is thought to form as a result of the oxidation of fat(s) and thus the concentration and antibody response should reflect the amount of fat in the diet.

Objective
The purpose of this study was to evaluate the antibody responses to MAA modified proteins following immunization and high fat western diet feeding in rats.

Methods
Male Sprague Dawley rats were immunized with MAA-modified protein weekly for 5 weeks and then assayed for antibodies to these proteins. Animals were then separated into the following groups: chow sham, chow MAA immunized, high fat sham, and high fat MAA immunized. The high fat animals were fed a Western diet with 2-thiouracil for 12 weeks, bled every 3 weeks, and serum assayed for the presence of circulating MAA antibodies.

Results
Prior to feeding with high fat diet, rats immunized with MAA-modified protein had a significant increase (P<0.001) in serum antibodies directed against these modified proteins compared to controls (N of 4 per group). Following feeding of high fat diet antibody concentrations increased 6 fold in the high fat MAA immunized group compared to the chow MAA immunized group (P<0.05). Antibodies in the high fat sham and chow sham had only minimal increases in antibodies to these proteins.

Conclusions
These data demonstrate that following immunization with MAA-modified proteins, circulating antibodies are produced that increase following consumption of a high fat Western diet. It suggests that MAA-modified proteins are produced at low levels following normal diet, producing antibodies which act as a normal clearance method for altered protein. When high fat consumption increases these antibody levels are increased in response to the oxidative stress.

Implications
Use of these antibodies as a biomarker in the future may help predict the onset or progression of atherosclerosis.
Abstract 424: Mechanisms of Restenosis in Type 2 Diabetes Mellitus
Authors: Wang Hongfeng , Kersten Judy R , Toth Jeffrey M , LaDisa John F 
Published: July 2021

Stents are widely employed to decrease cardiovascular risk in patients with type 2 diabetes mellitus (T2DM); however, restenosis limits their success. Mechanisms responsible for restenosis in T2DM are incompletely elucidated; however, low wall shear stress (WSS) and altered intracellular signaling likely contribute. We tested the hypothesis that neointimal hyperplasia (NH) after bare-metal stenting in T2DM is due to vascular remodeling (enhanced formation of advanced glycation end-products (AGEs), increased downstream vascular resistance (DVR), and decreased WSS) in T2DM; and that decreasing AGEs with ALT-711 (Alagebrium) mitigates this response.
Stents were implanted into the abdominal aorta of Zucker lean (ZL), obese (ZO), and diabetic (ZD) rats. After 21 days, blood flow and pressure data were recorded; and the stented region was sectioned for NH quantification or casted and imaged for WSS distributions by computational fluid dynamics modeling. Arterial segments (thoracic and abdominal aorta, carotid, iliac, femoral and arterioles) were harvested to detect AGEs related collagen cross-linking, and protein expression including TGFβ and receptor for AGE (RAGE).

DVR was elevated, whereas, WSS was significantly decreased in ZD compared to ZL and ZO rats, respectively (14.5±1.9 vs 30.6±1.6 and 25.4±2.2dyn/cm
2
; mean±SEM p<0.05). Intra-strut thickness (NH) was increased in ZO but not ZD rats. ALT-711 reduced DVR in ZD rats (15.6±2.5x10
5
to 8.39±0.6x10
5
dyn·s/cm
5
), decreased NH (ZL: 7.7±1.0 to 4.3±0.9%; ZO: 12.0±1.5 to 4.9±0.8%; ZD: 9.4±0.7 to 3.7±0.4%) and restored WSS in all rats. Increases in AGEs related collagen cross-linking were present in the arterioles of ZD rats, but reduced by treatment with ALT-711. No differences in RAGE or TGFβ expression were observed in treated compared to untreated rats.

In conclusion, ALT-711 decreased AGEs related collagen cross-linking, DVR, and normalized intra-stent WSS in rats with T2DM. These findings suggest that vascular remodeling may play an important role in modulating restenosis. Although TGFβ and RAGE expression did not appear to be modified by ALT-711, other intracellular signaling pathways that influence restenosis during T2DM remain to be explored.
Abstract 439: Niacin Does Not Accelerate Reverse Cholesterol Transport in Man
Authors: Dunbar Richard L , Cuchel Marina , Millar John S , Baer Amanda , Poria Rahul , Freifelder Richard H , Pryma Daniel A , Billheimer Jeffrey J , Rader Daniel J 
Published: July 2021

Background
HDL may be atheroprotective by accelerating reverse cholesterol transport (RCT). Niacin raises HDL cholesterol (HDL-c) and niacin monotherapy up to 3g/d prevented coronary events, possibly by accelerating RCT. However, up to 2g/d niacin did not prevent outcomes beyond aggressive LDL lowering including statins, arguing against RCT-mediated atheroprotection. We developed a novel method to assess macrophage-to-lipoprotein RCT in vivo. Preliminary studies in mice demonstrate that albumin-bound tritiated cholesterol (3H-Chol) is rapidly removed ( 95% in 30min) by resident macrophages. We monitored subsequent reappearance over 8d by macrophage-to-lipoprotein RCT as 3H-Chol rate of appearance (RA pre-post therapy, %3H-Chol injected/mol cholesterol/h) and tracer fecal excretion (%3H-Chol injected/g feces), and further analyzed RCT by multi-compartmental modeling.

Results
Niacin raised HDL-c 44% vs 17% on placebo (p=0.02) and dropped non HDL-c 40% (p<0.0001). Niacin and placebo did not differ by HDL 3H-Chol RA (placebo: 4.16-3.72, niacin: 3.24-2.61, p=0.8), total plasma 3H-Chol RA (placebo: 2.70-2.42, niacin: 2.35-2.14, p=0.9), macrophage-to-HDL transfer rate (placebo: 4.8-4.2, niacin: 5.1-4.7 fractional transfer/h, p=0.7), ex vivo cholesterol efflux capacity ratio (placebo: 0.73-0.82, niacin: 0.91-0.95, p=0.2), or tracer fecal excretion (placebo: 34.1-37.4, niacin: 21.2-28.0, p=0.6).

Conclusion
Despite potently raising HDL-c, high-dose niacin had no benefit on in vivo or ex vivo macrophage-to-lipoprotein RCT or fecal excretion in man, suggesting niacin’s atheroprotective potential lies elsewhere.
Abstract 477: HDL Inhibition of Murine Atherosclerosis Lesion Development is Dependent on Strain Background
Authors: Sontag Timothy J , Krishack Paulette A , Biswas Tapan K , Getz Godfrey S , Reardon Catherine A 
Published: July 2021

Inbred mouse strains vary greatly in their relative atherosensitivity, with C57BL/6 (C57) being the most sensitive and hence the preferred strain for most atherosclerosis studies. Among the resistant strains, FVBN/J (FVB) has been relatively well studied. On the ApoE knockout (E°) background, both mouse strains develop atherosclerotic lesions which are exacerbated by feeding a high fat/high cholesterol western-type diet (WTD). However, the FVB-E° mouse exhibits nearly 10-fold smaller lesions than the C57-E°. Additionally, FVB mice have plasma HDL cholesterol levels that are twice as high as C57. Wild type FVB mice have been shown to have lower inflammatory cell recruitment to the peritoneum upon thioglycollate treatment than C57. Our lab has generated ApoE/ApoA-I double knockout mice (EA°, lacking HDL) on both C57 and FVB background to compare the effect of HDL deficiency on lesion development. We hypothesize that the loss of HDL will have a greater effect on the more lesion susceptible C57 than the resistant FVB.
8 week C57 and FVB E° and EA° mice were kept on a WTD for 6 or 10 weeks and lesions were quantified in the innominate artery, ascending aorta, and aortic root. In all cases mice in the C57 background displayed significantly greater lesion size than mice in the FVB background, except in the ascending aorta of the E° mice at the earlier time point, despite higher plasma cholesterol levels in the FVB mice. The presence of ApoA-I was protective (E° vs EA°) in the C57 strain in the ascending aorta at both time points and its protection became significant in the innominate artery at the 10 week time point. No additional protection was afforded by ApoA-I in the FVB strain. ApoA-I deficiency in FVB mice did not affect inflammatory cell recruitment to the peritoneal cavity or plasma markers of LDL oxidation as greatly as in C57 mice. Plasma monocyte counts both before and after 6 weeks on WTD were higher in C57 mice with no effect of ApoA-I in either strain.
In conclusion, the FVB strain is less sensitive than C57 to lesion development at 3 major arterial sites with no protection afforded by HDL/ApoA-I, whereas HDL/ApoA-I is significantly protective in the C57 strain. This protection may result from the anti-inflammatory/anti-oxidative nature of C57 HDL that is not observed in FVB mice.
Abstract 490: Acute Superior Mesenteric Artery Occlusion Presenting as Strangulated Inguinal Hernia
Authors: Cao Shanjin , Huo Lihong , Ge Rongrong , Sun Li , Carrey Zev , Petrillo Richard 
Published: July 2021

An 85yo woman presented with diffused colicky abdominal pain and vomiting for 12hr. Patient still had bowel movement and passed flatus. Patient was otherwise healthy without past medical or surgical history, and taking no medications. PE: no distress, afebrile, vitals are stable. Cardiopulmonary exam only revealed tachycardia; Abdomen: soft, non-tender, no distension, bowel sounds hyperactive; there was an 8[[Unable to Display Character: &#61620;]]6 cm irreducible, firm but non-tender right inguinal hernia. Labs: leukocytosis, bicarbonate 20. CT abdomen with oral contrast suggested small bowel obstruction secondary to right inguinal hernia. The hernia was then reduced manually. Post the reduction patient had one foul smell watery bowel movement.
However, patient deteriorated quickly. Repeat labs: bicarbonate 8, anion gap 23, lactic acid 11, ABG: 7.01/29/246/7/99%. EKG: A-fib with tachycardia. Patient’s blood pressure dropped necessitating IV fluid and vasopressor support. Strangulated hernia with septic shock was suspected and emergency laparotomy was performed. Ascending, transverse and descending colon past the splenic curve were found necroses with foul-smelling turbid fluid intraperitoneally; the small bowel was minimally dilated with a kink 25cm beyond the ileocelcal valve with evidence of previous incarceration. Subtotal colectomy and partial small bowel resection with ileostomy was performed. Pathology confirmed terminal ileum and colonic gangrene; recent mesentery venous thrombi. Despite appropriate therapy, patient continued to be in septic shock and developed multiple organ failure, a stroke, and then brain death.
Acute mesenteric ischemia (AMI) is a rare abdominal emergency with high mortality, which could be caused by direct strangulation of the SMA by the inguinal hernia (Tiwary SK et al 2008) or thromoboembolism, e.g., emboli from A-fib, septic emboli, local thrombosis. Since there is no evidence that the incarcerated portion of small bowel had necrosis, this case is mostly likely caused by the paroxysmal A-fib-derived emboli. Due to the lack of typical clinical expression, a high index of suspicion is essential for prompt diagnosis. CT angiography is the current cornerstones for diagnosis of AMI, so treatment can be initiated expeditiously.
Abstract 499: Increased Lysine Acetylation After ‘Back-table’ Preparation of Human Saphenous Vein
Authors: Voskresensky Igor , Hocking Kyle , Osgood Michael , Cheung-Flynn Joyce , Komalavilas Padmini , Brophy Colleen 
Published: July 2021

BACKGROUND
Back-table preparation of human saphenous vein (SV) for surgical bypass results in conduit injury. We hypothesized that surgical manipulation results in increased total lysine acetylation, a global marker of injury. We examined effect of injury on acetylation of NFkB, a transcription factor involved in vascular smooth muscle proliferation.

METHODS
Paired SV samples were collected prior to surgical manipulation (UM) and after distention and marking (AM). SV rings were suspended in a muscle bath for measurement of contractile force in response to KCl and phenylephrine (PE); endothelial-dependent relaxation in response to carbachol (CCh); and endothelial-independent relaxation in response to sodium nitroprusside (SNP). Western blot analysis was used to measure total lysine and NFkB acetylation, results were normalized to GAPDH.

RESULTS

AM-SV generated significantly reduced physiologic parameters compared with UM-SV, including response to KCl (0.05 vs. 0.14 N/m
2
, n=9, p<0.05), PE (0.04 vs. 0.08 N/m
2
, n=7, p<0.05), endothelial-dependent relaxation (3.8% vs. 17.2%, n=7, p<0.05), and endothelial-independent relaxation (25.1% vs. 52.9%, n=7, p<0.05). Total lysine acetylation was increased in AM-SV compared to UM-SV (Fig1A), as was acetylation of NFkB (Fig1B).

CONCLUSIONS
Surgical preparation of SV results in physiologic dysfunction, and leads to increase in total lysine and NFkB acetylation. Increases in total lysine acetylation may be a global marker of injury and are associated with senescence. Increased acetylation of NFkB may correlate with the uncontrolled proliferative response of intimal the hyperplastic lesions.
Abstract 514: Cilostazol Attenuated Angiotensin II-induced Abdominal Aortic Aneurysms Thorough Anti-inflammatory Effect in Apolipoprotein E-deficient Mice
Authors: Umebayashi Ryoko , Uchida Haruhito A , Makino Hirofumi 
Published: July 2021

Objective
Chronic angiotensin II (AngII) infusion promotes development of abdominal aortic aneurysms (AAAs) in mice. Previous studies have shown that local inflammation plays an important role on formation of AAAs. Cilostazol, a phosphodiesterase-3 inhibitor with antiplatelet aggregation and vasodilatory effects, exerts vasoprotective effect by inhibiting inflammation and superoxide generation in several experimental studies. The purpose of this study was to evaluate whether cilostazol influenced AngII-induced AAAs.

Methods and Results
Male apolipoprotein E deficient mice (8-12 weeks old) were fed with either normal diet or cilostazol-containing (0.1% wt/v) diet. After 1 week of cilostazol administration, mice were infused subcutaneously with either AngII (1,000 ng/kg/min, n = 16 -19) or saline (n = 5 - 6) by osmotic minipumps for 4 weeks. AngII equivalently increased systolic blood pressure, irrespective of cilostazol administration. Cilostazol had no effect on serum cholesterol concentrations, triglycerides, high-density lipoprotein-cholesterol, body weights, heart rates, and systolic blood pressures. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas that were attenuated by cilostazol administration (1.94 ± 0.16 mm vs 1.53 ± 0.17 mm, P < 0.05). Cilostazol diminished AngII-induced increase of aortic MMP-2 activity and ICAM-1 protein expression as determined by gelatin zymography and Western blot, respectively (P < 0.05, each). Aortic mRNA expression of inflammatory cytokines such as MCP-1, IL-1β, osteopontin, and COX-2 was reduced by cilostazol administration (P < 0.05). In vitro, TNF-α increased MCP-1, ICAM-1 and VCAM-1 mRNA expression in mouse aortic endothelial cells. These enhancements were decreased by incubation with cilostazol (P < 0.05).

Conclusion
Cilostazol attenuated AngII-induced AAAs thorough its anti-inflammatory effect in male apolipoprotein E deficient mice.