Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of active absorbable algal calcium (AAA Ca) with collagen and other matrix components on aging-associated skin changes and backache and joint pain was tested in a case-controlled study of 40 test subjects and 40 age-matched control subjects (mean age, 65 years) complaining of backache and knee joint pain due to osteoarthritis, spondylosis deformans, and/or osteoporosis. Supplementation with 900 mg calcium (given as AAA Ca) and 3.5 g collagen and other matrix components, including glucosamine, daily for 4 months resulted in a marked alleviation of subjective pain, assessed by the face scale. A fall of skin impedance in response to exercise loads, such as standing up, walking, squatting, and climbing up and down stairs, reported as an objective manifestion of pain, was also alleviated. The basal skin impedance, which increases with age, was significantly reduced in response to the Ca-collagen-matrix supplementation, suggesting a change of skin properties similar to rejuvenation, along with subjective smoothening and moistening of the skin. Urinary excretion of N-terminal crosslinking telopeptide of type I collagen (NTx) was decreased in the Ca-collagen-matrix supplementation group, but not in the control group. In addition to calcium suppression of parathyroid hormone, preventing bone resorption, collagen, acting on the intestinal lymphatic system, may protect collagen from degradation through the inhibition of cytokine-induced release of metalloproteinases, including collagenase.
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PMID:The effect of active absorbable algal calcium (AAA Ca) with collagen and other matrix components on back and joint pain and skin impedance. 1220 36

The hallmark feature of abdominal aortic aneurysm (AAA) is the progressive degeneration of aortic wall. Matrix proteoglycans (PGs) play important roles in the development of vascular diseases and the function of the tissue. In this study, we examined the concentration, expression and localization of the small extracellular matrix PG biglycan and decorin. The concentration of small PGs present in normal and aneurysmal aortas was determined by biochemical methods following extraction of the tissues with guanidine hydrochloride and treatment with collagenase/elastase, isolation by ion-exchange and gel chromatographies and identification by Western blotting. The levels of mRNA encoding for biglycan and decorin were evaluated in corresponding tissue samples by reverse transcriptase polymerase chain reaction (RT-PCR). Distribution of extracellular matrix macromolecules was examined using Movat's pentachrome staining and localization of biglycan and decorin by immunohistochemistry. Both normal and aneurysmal aortas contained almost equal amounts of decorin (1.13+/-0.08 and 1.22+/-0.10 mg uronic acid per g of dry defatted (dd) tissue, respectively). Furthermore, the expression of decorin was almost constant in both tissues. In normal specimens decorin accounts for 22% of total PGs, whereas in AAA ones for 60%, due to the significant loss of other matrix PGs. In contrast, the concentration of biglycan was markedly decreased in aneurysmal aortas (57%, 0.478+/-0.04 mg uronic acid per g of dd tissue) in comparison to normal ones (1.12+/-0.10 mg uronic acid per g of dd tissue). Biglycan accounts for 22% of total PGs in normal aortas and 25% of total in aneurysmal tissue. A similar decrease (60%) in the amounts of mRNA encoding for biglycan was observed in the AAA. Immunohistochemical study showed that all aortic layers of AAA were characterized by a significant loss of elastin, biglycan and other PGs/GAGs and replacement of these molecules with collagen fibrils and decorin. The obtained data suggest that the altered matrix architecture of aorta, i.e. the differential expression of biglycan and localization of decorin may well be crucial parameters accounting for the functional degeneration of the tissue and the development of aneurysmal dilatation.
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PMID:Decreased biglycan expression and differential decorin localization in human abdominal aortic aneurysms. 1241 72

Between 1985 and 2000, a total of 871 patients underwent surgical treatment for infrarenal abdominal aortic aneurysm (AAA), including 98 (11.2%) presenting with ruptured abdominal aortic aneurysms (RAAA). An optimized operative protocol was used to treat 77 RAAA starting in January 1989. The main features of the optimized protocol are routine use of intraoperative autotransfusion, revascularization by aortoaortic bypass, absence of systemic heparinization, and use of a collagen-impregnated prosthesis. Intraoperative mortality (IOM) was 3.8%. Postoperative mortality at 1 month (POM1) was 25.9% and postoperative mortality at 3 months (POM3) was 33.7%. Heart failure (p <0.001), hemodynamic shock (p <0.001), and hemorrhage (p = 0.04) were the only complications correlated with POM1. Pneumonia (p = 0.01) and sepsis (p = 0.01) were the only complications correlated with POM3. Isolated acute renal insufficiency was not a significant risk factor for postoperative mortality. Using a cutoff of 75 years, there was a significant age-related difference (p = 0.025) for POM1 but not for IOM and POM3. The findings of this study show that optimizing the operative protocol decreases mortality related to RAAA. The main predictor of POM1 was hemodynamic status while the main predictor of POM3 was infection. Isolated acute renal insufficiency was not a risk factor for mortality. Age should not be considered a contraindication for operative treatment.
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PMID:Ruptured aneurysm of the infrarenal abdominal aorta: impact of age and postoperative complications on mortality. 1270 41

Ehlers-Danlos syndrome type IV (EDS-IV) is an autosomal-dominant disorder caused by a defect of type III collagen which leads to ruptures of arteries and hollow organs. Neurological presentation with muscle involvement and flexion contractures of the finger joints is uncommon. We clinically characterized seven members of a family with EDS-IV. The index patient, a young woman with an acrogeric face, suffered chronic muscle pain and cramps, Achilles tendon retraction, finger flexion contractures and seizures. The mother had similar features and had experienced an ischemic stroke. Biochemical study in cultured fibroblasts and molecular analysis of the COL3A1 gene led to the diagnosis of EDS-IV. A glycine substitution, p.G883V, within the triple helix of the alpha 1(III) chain, was found in the index patient and in the mother. The maternal grandfather and an aunt each had an abdominal aortic aneurysm, the rupture of which was the cause of death in the latter, at 40 years of age. Surprisingly, we found the mutation, as a mosaic, in the asymptomatic maternal grandmother. This expands the clinical spectrum of EDS type IV and confirms that in some families mosaicism can be identified as the source of the mutation.
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PMID:Neurological presentation of Ehlers-Danlos syndrome type IV in a family with parental mosaicism. 1278 57

Treatment options for crescentic glomerulonephritis include the use of steroids, cytotoxic therapy, and, in severe cases, intravenous immunoglobulins and plasmapheresis. Injury and lysis of capillary glomerular basement membrane, which is made up of type IV collagen, laminin, fibronectin, and proteoglycans, by serine proteinases and matrix metalloproteinases (MMPs) likely is an important participant in the pathogenesis of crescentic glomerulonephritis. Tetracycline derivatives inhibit not only the activity of MMPs, but also their production, and have been investigated for the treatment of disorders in which the MMP system becomes amplified, such as degenerative osteoarthritis, periodontitis, cancer, and abdominal aortic aneurysm. We report an interesting case of crescentic glomerulonephritis in a young man who was treated with cyclophosphamide and prednisone. The patient developed steroid-induced acne that was treated with long-term oral doxycycline therapy. During the period the patient was administered doxycycline, proteinuria decreased by 70% and recurred when doxycycline was stopped. To our knowledge, this is the first report of possible benefits of a metalloproteinase inhibitor (doxycycline) in glomerulonephritis in humans. Future studies are urgently required to explore the option of metalloproteinase inhibitors in the treatment of proliferative glomerulonephritis.
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PMID:Doxycycline decreases proteinuria in glomerulonephritis. 1290 Aug 22

Abdominal aortic aneurysms (AAAs) occur in 5-7% of people over age 60 in the United States. Early intervention in the disease process could have a significant impact on the incidence of complications and on patient survival, but identifying incipient aneurysms can be difficult. ApoE knockout mice develop AAAs following infusion of angiotensin II (AngII) by osmotic minipump into the subcutaneous space of mice at doses ranging from 500 to 1000 ng kg(-1) min(-1) for 7-28 days. These mice are used as models of AAA development. This study tested the hypothesis that near-IR spectrometry and PCR can determine AngII dose (SEE = 26 ng kg(-1) min(-1), SEP = 37 ng kg(-1) min(-1), r2 = 0.99) and collagen/elastin (C/E) ratio (SEE = 0.38, SEP = 0.39, r2 = 0.85) in mouse aortas.
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PMID:Near-infrared spectrometry of abdominal aortic aneurysm in the ApoE-/- mouse. 1457 Feb 22

Degradation of the extracellular matrix components elastin and collagen has been implicated in vascular diseases, including abdominal aortic aneurysm (AAA) and atherosclerotic plaque rupture. Increased expression of matrix metalloproteinases (MMPs) is involved in these disease processes. Our previous studies have demonstrated that MMP-2 derived from mesenchymal cells is required for aneurysm development in a murine model. Doxycycline is a nonspecific inhibitor of MMPs. In the present study, the mechanisms of the inhibitory effects of doxycycline on MMP-2 expression from cultured human aortic smooth muscle cells (SMCs) and human aortic aneurysm tissue explants were studied. Doxycycline inhibited MMP-2 expression from cultured SMCs in a concentration-dependent manner (5-40 microg/mL; inhibitory concentration of 50%, 6.5 microg/mL). At normal therapeutic serum concentration (5 microg/mL) doxycycline significantly reduced MMP-2 production from SMCs (37%; P <.05), which were stimulated with conditioned media from macrophage or lymphocyte co-culture simulating the inflammatory milieu of AAA tissue. This correlated with a decrease in MMP-2 mRNA half-life, from 49 hours to 28 hours, which suggests that doxycycline inhibits SMC MMP-2 production in part by reducing MMP-2 mRNA stability. When AAA tissue was cultured for 10 days with doxycycline at concentrations of 2.5 to 40 microg/mL, the media exhibited a concentration-dependent decrease in both active and latent forms of MMP-2 and MMP-9. Doxycycline at a concentration of 5 microg/mL reduced active and latent MMP-2 secreted from cultured AAA tissue by 50% and 30%, respectively (P <.05). These study findings demonstrate that doxycycline at standard therapeutic serum concentrations inhibits MMP-2 expression from cultured human aortic SMCs and AAA tissue explants. Inasmuch as MMP activity contributes to extracellular matrix degradation in AAAs and atherosclerotic plaque, doxycycline may have potential value in treating these diseases.
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PMID:Mechanism of inhibition of matrix metalloproteinase-2 expression by doxycycline in human aortic smooth muscle cells. 1468 44

Many mouse models of abdominal aortic aneurysms have been developed that use a diverse array of methods for producing the disease, including genetic manipulation and chemical induction. These models could provide insight into potential mechanisms in the development of this disease. Although experimental studies on abdominal aortic aneurysms (AAAs) have used a variety of mammalian and avian approaches, there is an increasing reliance on the use of mice. The models recapitulate some facets of the human disease including medial degeneration, inflammation, thrombus formation, and rupture. Most of the mouse models of AAA are evoked either by genetically defined approaches or by chemical means. The genetic approaches are spontaneous and engineered mutations. These include defects in extracellular matrix maturation, increased degradation of elastin and collagen, aberrant cholesterol homeostasis, and enhanced production of angiotensin peptides. The chemical approaches include the intraluminal infusion of elastase, periaortic incubations of calcium chloride, and subcutaneous infusion of AngII. A common feature of these models is the reduction of AAA incidence and severity by the prophylactic administration of matrix metalloproteinase (MMP) inhibitors or genetically engineered deficiencies of specific members of this proteolytic protein family. The validation of mouse models of AAAs will provide insight into the mechanisms of progression of the human disease.
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PMID:Mouse models of abdominal aortic aneurysms. 1473 19

Abdominal aortic aneurysm is accompanied by the impairment of collagen metabolism in arterial wall. Metalloproteinases and collagen-stimulating factors play an important role in the maintenance of balance between collagen biosynthesis and degradation in tissues. Insulin-like growth factor-I (IGF-I) plays a major role in the stimulation of collagen biosynthesis. Its activity and bioavailability to target cells are modulated by IGF binding proteins (IGFBPs). The potential role of these factors in the mechanism of collagen metabolism deregulation in aortic aneurysm is the purpose of this study. Therefore, we have compared the content of collagen, gelatinolytic activity, IGF-I, IGFBP-1 and IGFBP-3 in normal human aorta and aortic aneurysm. The content of hydroxyproline (representing collagen content) in the proteins of aortic aneurysm was found to be similar to that found in normal aorta. Taking into account that some of the hydroxyproline may be derived from collagen degradation products (CDPs), they were separated and hydroxyproline was determined. It has been found that CDP-derived hydroxyproline content in aortic aneurysm was increased as compared with normal aorta, suggesting an increased collagen degradation. In contrast, zymography showed a decrease of collagenolytic activity in aortic aneurysm tissue, but an increase in mural thrombus, compared to respective controls. IGF-I concentration in aortic aneurysm was decreased, while the concentrations of BP-1 and BP-3 were both increased compared to control. The data suggest that increased collagen degradation in aortic aneurysm is due to the increase in collagenolytic activity in mural thrombus accompanying aneurysm tissue. It suggests that the mural thrombus may play a critical role in the pathogenesis of abdominal aortic aneurysm.
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PMID:Metalloproteinases, insulin-like growth factor-I and its binding proteins in aortic aneurysm. 1525 69

Among the fatal vascular complications associated with autosomal dominant polycystic disease (ADPKD), ruptured intracerebral aneurysm and ruptured abdominal aortic aneurysm are widely known. However, there are few reports on the dissecting thoracic aortic aneurysm as a fatal complication of ADPKD. We report a case of a 58-year-old man with a history of ADPKD who presented to the emergency department with out-of-hospital cardiac arrest. Immediate cardiopulmonary resuscitation restored a spontaneous circulation successfully and subsequent image study revealed a type I dissecting thoracic aortic aneurysm. Emergency aortic grafting was performed--but he died from postoperative haemorrhage. The surgical specimen of the aorta showed cystic medial necrosis. This rare case emphasizes the need to consider such a diagnosis in a patient with ADPKD who presents to the emergency department with sudden cardiac arrest. In addition, the histological finding indicates the aetiological role of a collagen defect in addition to chronic hypertension in the pathogenesis of aortic dissection in ADPKD patients.
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PMID:Sudden death caused by dissecting thoracic aortic aneurysm in a patient with autosomal dominant polycystic kidney disease. 1545 91


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