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Journal of Vascular Surgery Dec 2018Previous in vitro and animal studies have suggested that osteopontin (OPN), an inflammatory extracellular matrix protein, is involved in the formation and growth of...
OBJECTIVE
Previous in vitro and animal studies have suggested that osteopontin (OPN), an inflammatory extracellular matrix protein, is involved in the formation and growth of abdominal aortic aneurysms (AAAs). However, the mechanism by which this occurs continues to be nebulous. The relationship between OPN and inflammation-suppressing lymphocytes present in the human AAA condition was investigated and presented herein.
METHODS
Serum OPN concentrations were measured in healthy, risk factor-matched non-AAA and AAA patients by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to determine the source of OPN secretion using aortic tissue collected from multiorgan donors and AAA patients undergoing open surgical repair. Vascular smooth muscle cells (VSMCs) were exposed to various inflammatory mediators, and OPN expression was evaluated by quantitative reverse transcriptase-polymerase chain reaction and ELISA. The inflammatory nature of OPN and the aortic wall was determined using a TR1 suppressor cell induction assay as a surrogate and characterized by ELISA and fluorescence-activated cell sorting.
RESULTS
OPN was found to be elevated in both the plasma and aortic homogenate of AAA patients compared with controls. On immunohistochemistry, OPN localized to the tunica media of the diseased aorta but was minimally expressed in healthy aorta. In vitro, cigarette smoke extract was the most potent stimulator of OPN secretion by VSMCs and increased both messenger RNA and supernatant concentrations. OPN demonstrated an ability to inhibit the induction of interleukin 10-secreting TR1 lymphocytes, a depleted population in the AAA patient, from naive precursors. Last, neutralizing receptor targets of OPN in the setting of AAA homogenate coincubation abrogated the inhibition of TR1 induction.
CONCLUSIONS
OPN, secreted by the VSMCs of the tunica media, is elevated in the circulating plasma and aortic wall of patients with AAA. It can inhibit the induction of the TR1 suppressor cell, leading to an overall proinflammatory state contributing to progressive aortic wall breakdown and dilation.
Topics: Aorta, Abdominal; Aortic Aneurysm, Abdominal; Case-Control Studies; Cells, Cultured; Dilatation, Pathologic; Humans; Interleukin-10; Lymphocyte Activation; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Osteopontin; Signal Transduction; T-Lymphocytes; Up-Regulation; Vascular Remodeling
PubMed: 29402664
DOI: 10.1016/j.jvs.2017.10.068 -
Circulation Oct 2018Long noncoding RNAs have emerged as critical molecular regulators in various biological processes and diseases. Here we sought to identify and functionally characterize...
BACKGROUND
Long noncoding RNAs have emerged as critical molecular regulators in various biological processes and diseases. Here we sought to identify and functionally characterize long noncoding RNAs as potential mediators in abdominal aortic aneurysm development.
METHODS
We profiled RNA transcript expression in 2 murine abdominal aortic aneurysm models, Angiotensin II (ANGII) infusion in apolipoprotein E-deficient ( ApoE) mice (n=8) and porcine pancreatic elastase instillation in C57BL/6 wild-type mice (n=12). The long noncoding RNA H19 was identified as 1 of the most highly upregulated transcripts in both mouse aneurysm models compared with sham-operated controls. This was confirmed by quantitative reverse transcription-polymerase chain reaction and in situ hybridization.
RESULTS
Experimental knock-down of H19, utilizing site-specific antisense oligonucleotides (LNA-GapmeRs) in vivo, significantly limited aneurysm growth in both models. Upregulated H19 correlated with smooth muscle cell (SMC) content and SMC apoptosis in progressing aneurysms. Importantly, a similar pattern could be observed in human abdominal aortic aneurysm tissue samples, and in a novel preclinical LDLR (low-density lipoprotein receptor) Yucatan mini-pig aneurysm model. In vitro knock-down of H19 markedly decreased apoptotic rates of cultured human aortic SMCs, whereas overexpression of H19 had the opposite effect. Notably, H19-dependent apoptosis mechanisms in SMCs appeared to be independent of miR-675, which is embedded in the first exon of the H19 gene. A customized transcription factor array identified hypoxia-inducible factor 1α as the main downstream effector. Increased SMC apoptosis was associated with cytoplasmic interaction between H19 and hypoxia-inducible factor 1α and sequential p53 stabilization. Additionally, H19 induced transcription of hypoxia-inducible factor 1α via recruiting the transcription factor specificity protein 1 to the promoter region.
CONCLUSIONS
The long noncoding RNA H19 is a novel regulator of SMC survival in abdominal aortic aneurysm development and progression. Inhibition of H19 expression might serve as a novel molecular therapeutic target for aortic aneurysm disease.
Topics: Angiotensin II; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Apoptosis; Case-Control Studies; Cells, Cultured; Dilatation, Pathologic; Disease Models, Animal; Disease Progression; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Mice, Inbred C57BL; Mice, Knockout, ApoE; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Pancreatic Elastase; RNA, Long Noncoding; Receptors, LDL; Swine; Swine, Miniature; Tumor Suppressor Protein p53; Up-Regulation
PubMed: 29669788
DOI: 10.1161/CIRCULATIONAHA.117.032184 -
Annals of Vascular Surgery Jan 2018Hypertension (HTN) has long been associated with abdominal aortic aneurysm (AAA) development, and these cardiovascular pathologies are biochemically characterized by... (Comparative Study)
Comparative Study
BACKGROUND
Hypertension (HTN) has long been associated with abdominal aortic aneurysm (AAA) development, and these cardiovascular pathologies are biochemically characterized by elevated plasma levels of angiotensin II (AngII) as well as interleukin-6 (IL-6). A biologic relationship between HTN and AAA has not been established, however. Accordingly, the objective of this study was to evaluate whether elevated tension may initiate IL-6 production to accumulate monocyte/macrophages and promote dilation of the abdominal aorta (AA).
METHODS
An IL-6 infusion model (4.36 μg/kg/day) was created utilizing an osmotic infusion pump, and after 4 weeks, AA diameter was measured by digital microscopy. The AA was then excised for CD68 immunostaining and flow cytometric analysis with CD11b and F4/80 to identify macrophages. Aortic segments from wild-type mice were suspended on parallel wires in an ex vivo tissue myograph at experimentally derived optimal tension (1.2 g) and in the presence of elevated tension (ET, 1.7 g) for 3 hr, and expression of IL-6 and monocyte chemoattractant protein-1 (MCP-1) was evaluated by quantitative polymerase chain reaction (QPCR). Isolated aortic vascular smooth muscle cells (VSMCs) were subjected to 12% biaxial cyclic stretch or held static (control) for 3 hr (n = 7), and IL-6 and MCP-1 expressions were evaluated by QPCR.
RESULTS
Four-week IL-6 infusion resulted in an AA outer diameter that was 72.5 ± 5.6% (P < 0.05) greater than that of control mice, and aortic dilation was accompanied by an accumulation of macrophages in the AA medial layer as defined by an increase in CD68 + staining as well as an increase by flow cytometric quantification of CD11b+/F4/80+ cells. Wild-type AA segments did not respond to ex vivo application of ET but cyclic stretch of isolated VSMCs increased IL-6 (2.03 ± 0.3 fold) and MCP-1 (1.51 ± 0.11 fold) expression compared to static control (P < 0.05). Pretreatment with the selective STAT3 inhibitor WP1066 blunted the response in both cases. Interestingly, AngII did not stimulate expression of IL-6 and MCP-1 above that initiated by tension and again, the response was inhibited by WP1066, supporting an integral role of STAT3 in this pathway.
CONCLUSIONS
An IL-6 infusion model can initiate macrophage accumulation as well as aortic dilation, and under conditions of elevated tension, this proinflammatory cytokine can be produced by aortic VSMCs. By activation of STAT3, MCP-1 is expressed to increase media macrophage abundance and create an environment susceptible to dilation. This biomechanical association between HTN and aortic dilation may allow for the identification of novel therapeutic strategies.
Topics: Angiotensin II; Animals; Antigens, CD; Antigens, Differentiation; Antigens, Differentiation, Myelomonocytic; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Arterial Pressure; CD11b Antigen; Cells, Cultured; Chemokine CCL2; Dilatation, Pathologic; Disease Models, Animal; Female; Interleukin-6; Macrophages; Male; Mechanotransduction, Cellular; Mice; Monocytes; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phosphorylation; STAT3 Transcription Factor; Stress, Mechanical
PubMed: 29107003
DOI: 10.1016/j.avsg.2017.10.001 -
Cureus Nov 2022Abdominal tuberculosis, a form of extrapulmonary tuberculosis is common in developing countries like India. Manifestations of abdominal tuberculosis are widely variable....
Abdominal tuberculosis, a form of extrapulmonary tuberculosis is common in developing countries like India. Manifestations of abdominal tuberculosis are widely variable. Its incidence is high among human immunodeficiency virus (HIV) infected patients in the adult population. Here, we report a 26-year-old male, initially treated in a private clinic for abdominal distention, loss of appetite, and loss of weight for one month. Magnetic resonance imaging (MRI) of the abdomen showed a large loculated fluid collection. Computed tomography (CT) of the chest showed signs of pulmonary tuberculosis. The patient was started on anti-tuberculosis therapy (ATT) and discharged. Ten days later, the patient presented to our hospital with foul-smelling pus discharging from the umbilicus and necrosis of the surrounding tissue. Abdominal examination revealed a tense, distended, and tender abdomen. The patient was referred for emergency laparotomy. The intraoperative findings showed features that were a combination of plastic fibrous type and encysted loculated type of peritoneal tuberculosis. The above-mentioned case describes a very uncommon presentation of abdominal tuberculosis. A high degree of suspicion is required for diagnosing such conditions, especially in immunocompromised individuals. The case report also highlights the difficulties in the diagnosis of abdominal tuberculosis.
PubMed: 36505153
DOI: 10.7759/cureus.31184 -
The Veterinary Clinics of North... Apr 1988Based on the clinical impression and the current knowledge of the clinical variables (rectal examination, abdominal distention, abdominal fluid, intractable pain) most... (Review)
Review
Based on the clinical impression and the current knowledge of the clinical variables (rectal examination, abdominal distention, abdominal fluid, intractable pain) most likely to differentiate between medical and surgical cases, three decision trees are provided as a guide to making the management decision in a horse with abdominal pain. Prior elimination of horses with limited life expectancy because of age or function or where financial constraints are present is understood. It must be emphasized that most of the information presently available originates from referral centers where the prevalence of surgical candidates is much higher than in general practice. This would influence the accuracy of the clinician in identifying horses with a surgical lesion or estimating survival (positive predictive value).
Topics: Abdomen, Acute; Animals; Horse Diseases; Horses; Prognosis
PubMed: 3289696
DOI: 10.1016/s0749-0739(17)30649-1 -
Alimentary Pharmacology & Therapeutics Oct 2009While knowledge has accumulated regarding health care seeking in several functional gastrointestinal disorders (FGIDs), little is known about health care seeking in...
BACKGROUND
While knowledge has accumulated regarding health care seeking in several functional gastrointestinal disorders (FGIDs), little is known about health care seeking in those with bloating and distention.
AIM
To identify predictors of health care seeking for bloating and distention.
METHODS
The validated Talley Bowel Disease Questionnaire was mailed to a cohort selected at random from the population of Olmsted County, Minnesota; 2259 subjects (53% females; mean age 62 years) answered questions about bloating and distention. The complete medical record of each respondent was reviewed. Logistic regression was used to compare consulting for bloating and distention with consulting for other GI symptoms, and nonconsulters.
RESULTS
A total of 131 (6%) subjects in the community consulted a physician for bloating or distention. Older age [odds ratio (OR), 1.8; 95% confidence interval (CI): 1.5, 2.1], higher somatic symptom scores (OR, 2.0; CI: 1.4, 2.8), lower education level (OR, 2.7; CI: 1.2, 5.6), early satiety (OR, 2.0; CI: 1.1, 3.8) and abdominal pain (OR, 2.4; CI: 1.6, 3.7) were associated with people seeking health care for bloating or distention vs. non-consulters. Similarly, older age (OR, 1.4; CI: 1.2, 1.7), chronic constipation (OR, 2.0; CI: 1.2, 3.2) and visible distention (OR, 3.0; CI: 1.8, 4.9) had greater odds of presenting for bloating or distention compared with presenting for other GI symptoms; somatic symptoms were not a predictor (OR, 1.1; CI: 0.8, 1.5).
CONCLUSIONS
Factors that lead people to present for bloating and distention are similar to those for other GI symptoms visits; however, specific biological rather than somatic features may predict visits for bloating and distention.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dilatation, Pathologic; Epidemiologic Methods; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Minnesota; Patient Acceptance of Health Care; Young Adult
PubMed: 19563502
DOI: 10.1111/j.1365-2036.2009.04080.x -
Radiology Case Reports Jun 2022Trichobezoars are usually formed due to ingestion of hair or hair-like fibres and present with a wide spectrum of clinical manifestations. We report a case of Rapunzel's...
Trichobezoars are usually formed due to ingestion of hair or hair-like fibres and present with a wide spectrum of clinical manifestations. We report a case of Rapunzel's syndrome associated with trichotillomania in a 16-year-old girl who presented to our Haematology unit with complaints of fatigue, abdominal distention, and early satiety. Initial evaluation demonstrated anaemia, thrombocytosis, and a left hypochondrial mass suggestive of splenomegaly. However, ultrasound of the abdomen showed no hepatosplenomegaly and blood investigations were not suggestive of haematological malignancy. Not long after, the patient presented to the emergency department with suspected acute abdomen. Computed tomography of the abdomen revealed intraluminal gastric and jejunal masses causing small bowel obstruction. Emergency laparotomy confirmed gastric and jejunal trichobezoars, and subsequent psychiatric evaluation confirmed trichotillomania. Clinicians should consider trichobezoar in the differential diagnosis of abdominal pain and a non-tender 'spleen-like' abdominal mass.
PubMed: 35496748
DOI: 10.1016/j.radcr.2022.03.097 -
Biomedicine & Pharmacotherapy =... May 2021Aneurysms are generally the result of dilation of all 3 layers of the vessel wall, and pseudoaneurysms are the result of localized extravasation of blood that is...
OBJECTIVES
Aneurysms are generally the result of dilation of all 3 layers of the vessel wall, and pseudoaneurysms are the result of localized extravasation of blood that is contained by surrounding tissue. Since there is still no recommended protocol to decrease aneurysm formation and progression, we hypothesised that intramural delivery of TGF β1 hydrogel can decrease aneurysm and pseudoaneurysm formation and progression.
MATERIALS
Male C57BL/6 J mice (12-14 wk), SD rats (200 g) and pig abdominal aortas were used, and hydrogels were fabricated by the interaction of sodium alginate (SA), hyaluronic acid (HA) and CaCO.
METHODS
A CaCl adventitial incubation model in mice and a decellularized human great saphenous vein patch angioplasty model in rats were used. TGF β1 hydrogel was intramurally delivered after CaCl incubation in mice; at day 7, the abdomen in some mice was reopened, and TGF β1 hydrogel was injected intramurally into the aorta. In rats, TGF β1 hydrogel was delivered intramurally after patch angioplasty completion. Tissues were harvested at day 14 and analysed by histology and immunohistochemistry staining. The pig aorta was also intramurally injected with hydrogel.
RESULTS
In mice, rhodamine hydrogel was still found between the medium and adventitia at day 14. In the mouse aneurysm model, there was a thicker wall and smaller amount of elastin breaks in the TGF β1 hydrogel-delivered groups both at day 0 and day 7 after CaCl incubation, and there were larger numbers of p-smad2- and TAK1-positive cells in the TGF β1 hydrogel-injected groups. In the rat decellularized human saphenous vein patch pseudoaneurysm model, there was a higher incidence of pseudoaneurysm formation when the patch was decellularized using 3% SDS, and delivery of TGF β1 hydrogel could effectively decrease the formation of pseudoaneurysm formation and increase p-smad2 and TAK1 expression. In pig aortas, hydrogels can be delivered between the medium and adventitia easily and successfully.
CONCLUSIONS
Intramural delivery of TGF β1 hydrogel can effectively decease aneurysm and pseudoaneurysm formation and progression in both mice and rats, and pig aortas can also be successfully intramurally injected with hydrogel. This technique may be a promising drug delivery method and therapeutic choice to decrease aneurysm and pseudoaneurysm formation and progression in the clinic.
Topics: Aneurysm, False; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Delayed-Action Preparations; Dilatation, Pathologic; Disease Models, Animal; Disease Progression; Drug Carriers; Drug Compounding; Hydrogels; MAP Kinase Kinase Kinases; Male; Mice, Inbred C57BL; Phosphorylation; Rats, Sprague-Dawley; Smad2 Protein; Sus scrofa; Transforming Growth Factor beta1; Mice; Rats
PubMed: 33545663
DOI: 10.1016/j.biopha.2021.111296 -
Journal of the American College of... Nov 2018
Topics: Aortic Aneurysm, Abdominal; Dilatation; Dilatation, Pathologic; Humans; Nanoparticles
PubMed: 30466518
DOI: 10.1016/j.jacc.2018.08.2187 -
Bulletin Du Cancer Jun 2011Malignant ascites are the cancer-associated accumulation of fluids in the peritoneal cavity. The neoplasms most frequently associated with ascites are ovarian, breast,... (Review)
Review
Malignant ascites are the cancer-associated accumulation of fluids in the peritoneal cavity. The neoplasms most frequently associated with ascites are ovarian, breast, colon, stomach and pancreas adenocarcinomas. Symptoms are abdominal distention, nausea, vomiting, anorexia, dyspnea and limbs oedemas. Several pathophysiological mechanisms might be implicated such as peritoneal carcinomatosis, lymphatic vessels' obstruction, portal hypertension or heart failure. Its diagnosis is most often performed in a context of already known neoplasia. Malignant ascites are associated with a pejorative evolution. Ascites which cannot be mobilized or show early recurrence and cannot be prevented by medical treatment are defined as refractory ascites. Therefore, management of refractory malignant ascites takes place in the context of palliative care and aims at improving the quality of life of these patients. This review lists the current data reported on the pathophysiology of malignant ascites and describes the present and future options for refractory malignant ascites management.
Topics: Antineoplastic Agents; Ascites; Breast Neoplasms; Diuretics; Female; Gastrointestinal Neoplasms; Humans; Immunotherapy; Injections, Intraperitoneal; Lung Neoplasms; Male; Molecular Targeted Therapy; Ovarian Neoplasms; Palliative Care; Paracentesis; Peritoneal Cavity; Peritoneovenous Shunt; Quality of Life; Recurrence; Vascular Endothelial Growth Factor A
PubMed: 21636346
DOI: 10.1684/bdc.2011.1373