PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Vascular System Injuries”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMedDate not supplied

The role of the renin-angiotensin system in malignant vascular injury affecting the systemic and cerebral circulations.

Malignant hypertension is a rare but serious syndrome complicating 1% of essential hypertension and causing neurological, renal and cardiac complications. Despite improved anti-hypertensive medication, the incidence of this condition fails to decline. In the first part of this review, we discuss transgenic rat models of malignant hypertension, generated by over-expressing renin, to illustrate the role of the renin-angiotensin system in the development of systemic hypertensive vascular remodelling and hypertension. In the second part, we focus on the cerebrovascular response to hypertension and discuss new data using a conditional, transgenic model of malignant hypertension, the inducible hypertensive rat (IHR). Cerebral infarction associates strongly with hypertension in man and the mechanisms by which hypertension predisposes to different types of stroke remains poorly understood. Rats have similar cerebrovascular anatomy and structure to humans and as such provide a good experimental tool. To date, such models lack controllability and blood-pressure matched controls. Using the IHR, we have manipulated dietary salt and water intake to generate a novel, controllable stroke phenotype. Hypertensive small-vessel stroke develops over a predictable time period, permitting the study of developing cerebrovascular lesions. Systemic end-organ injury and hypertension are not affected. Dissociation of the systemic and central vascular responses in this way, will allow for comparative study of animals with equivalent hypertension, genetic background and systemic features of hypertension with or without stroke.

Animals↗
PubMed1998

Function of the plasminogen/plasmin and matrix metalloproteinase systems after vascular injury in mice with targeted inactivation of fibrinolytic system genes.

The matrix metalloproteinase (MMP) system, which may be activated via the plasminogen (Plg)/plasmin system, is claimed to play a role in matrix degradation and smooth muscle cell migration. To test the role of both systems, expression of fibrinolytic and gelatinolytic activity was quantified after vascular injury in mice with targeted inactivation of tissue-type Plg activator (tPA-/-), urokinase-type Plg activator (uPA-/-), or Plg (Plg-/-). Neointima formation 1 week after vascular injury was impaired in uPA-/- and Plg-/- mice compared with wild-type (WT) mice or tPA-/- mice (reduction of neointimal area to 30% and 10% of WT, respectively). Cell accumulation at the borders of the injury was significantly (P<0.01) impaired compared with that in WT mice. One week after injury of the femoral artery, tPA-mediated fibrinolytic activity in arterial sections or extracts of WT, uPA-/-, or Plg-/- mice was not altered, whereas uPA activity levels in tPA-/- and Plg-/- mice were 2- to 3-fold higher than in uninjured controls. Total levels (latent plus active) of MMP-2 (gelatinase A) were increased by 2- to 4-fold, whereas the contribution of active MMP-2 represented 38% to 63% of the total in the different genotypes. MMP-9 (gelatinase B) was not detectable in the majority of control arteries, whereas total MMP-9 levels after injury were dramatically increased (up to 50-fold above the detection limit). Active MMP-9 represented 20% to 46% of total MMP-9 in WT, tPA-/-, and uPA-/- mice but was not consistently detectable in Plg-/- mice. Similar results were obtained in carotid arteries. Thus, the unaltered ratios of active and latent MMP-2 suggest that proMMP-2 activation may occur in the absence of tPA, uPA, or Plg, whereas no active MMP-9 was detected in the absence of Plg. The data of this study confirm a role for uPA and Plg but not for tPA in smooth muscle cell migration and neointima formation after vascular injury and indicate that impairment of these phenomena may occur despite the observed increases in MMP-2 or MMP-9 levels after vascular injury.

Animals↗
PubMed1991

Abdominal trauma revisited.

This article retrospectively reviews 258 consecutive abdominal trauma admissions who required laparotomy from July 1985 to June 1989 at a level one urban trauma center to define the population at risk, the patterns of injury, and the resulting morbidity and mortality. The findings were compared with a series of 252 abdominal trauma patients reported in 1974 by one of the authors. The majority of injuries in this series were gunshot wounds (GSWs) (47%), followed by stab wounds (SWs) (43%) and blunt abdominal trauma (10%). Males predominated, and 96% of patients were black. Major vascular system injury was the primary cause of death. Prompt evaluation, resuscitation, and operative intervention are mandatory in all abdominal GSW patients. More than half of those patients with major vascular system injury did not present in shock but had a high associated mortality.

Abdominal Injuries↗
PubMed2004

Vascular injury in systemic sclerosis: angiotensin-converting enzyme insertion/deletion polymorphism.

The microvascular involvement in systemic sclerosis (SSc) is characterized by endothelial damage and smooth muscle cell migration in the intima. The vascular pathologic modifications in SSc are strikingly similar to those of atherosclerosis. SSc also is characterized by an accelerated macrovascular disease. The gene encoding for angiotensin-converting enzyme (ACE) is a 21-kb, 26-exon gene, localized on chromosome 17 (17q23). Polymorphic sites are an insertion/deletion (I/D) that consists of three genotypes: DD and II homozygotes, and ID heterozygote. ACE gene polymorphisms have been linked to vascular disorders (coronary artery disease, hypertension, cerebrovascular disease, hypertrophic cardiomyopathy, and diabetic or nondiabetic nephropathy). In particular, the possession of ACE D allele was associated with an increased risk of developing malignant vascular injury. ACE D allele frequency of the I/D polymorphism was associated with an increased risk of SSc, suggesting a genetic contribution to the disease. The discrepancy between the high prevalence of D allele and reduced ACE plasma levels in SSc demonstrate the lack of knowledge on the regulation and function of renin-angiotensin system in SSc.

Endothelium, Vascular↗
PubMed2000

Circulating endothelial cells and vascular injury in systemic lupus erythematosus.

In flares of systemic lupus erythematosus (SLE), endothelial cells activated by immune stimuli are potential participants in the inflammatory processes, which contribute to injury. Elevated levels of circulating endothelial cells (CEC) may be a proxy for vascular injury, as demonstrated in patients with sickle cell anemia during acute crises. In active SLE, CEC levels in peripheral blood are elevated (vs healthy controls and correlate with plasma C3a). CEC may reflect widespread unrecognized, ongoing injury despite the absence of clinical stigmata of vasculitis in patients with SLE.

Biomarkers↗
PubMed2004

[A case of chronic renal insufficiency due to vascular injury of systemic sclerosis].

A 48-year-old woman with systemic sclerosis (SSc) and rheumatoid arthritis was admitted to our hospital because of renal dysfunction. She had no hypertension at the time of admission and mild hypertension for only one and a half months until the time of admission. After admission, she received angiotensin-converting enzyme-inhibitor, but her renal dysfunction did not improve. She then had thrombotic microangiopathy with thrombocytopenia, and was treated with plasma exchange five times, but her renal dysfunction persisted. The renal biopsy specimens showed an arteriosclerotic lesion with intimal thickening and luminal narrowing and ischemic glomerular changes. These findings suggest that there is chronic vascular injury in a patient who has no hypertension with SSc and that once hypertension supervenes, whether severe or not, exacerbation of the vascular injury and renal dysfunction may occur.

Arthritis, Rheumatoid↗
PubMed2000

Roles of the AGE-RAGE system in vascular injury in diabetes.

This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy. AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE-exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE-RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic.

Animals↗
PubMed1997

Expression of intercellular adhesion molecule-1 (ICAM-1) on vascular endothelial cells and renal tubular cells in the generalized Shwartzman reaction as an experimental disseminated intravascular coagulation model.

The participation of adhesion molecules in systemic vascular injuries of the generalized Shwartzman reaction was studied. The generalized Shwartzman reaction was induced in mice by two consecutive injections of lipopolysaccharide. Intercellular adhesion molecule-1 (ICAM-1) was expressed on vascular endothelial cells, renal tubular cells and alveolar wall in generalized Shwartzman reaction-induced mice. The preparative injection of lipopolysaccharides induced ICAM-1 expression in those cells, and the provocative injection of lipopolysaccharides for the generalized Shwartzman reaction augmented it further. The simultaneous administration of anti-gamma interferon antibody with the preparative injection of lipopolysaccharides completely inhibited ICAM-1 expression on vascular endothelial cells. The injection of recombinant gamma interferon in replacement of lipopolysaccharides resulted in ICAM-1 expression. The administration of anti-ICAM-1 antibody together with the provocative injection of lipopolysaccharides significantly blocked the apoptosis of vascular endothelial cells in generalized Shwartzman reaction-induced mice. It was suggested that ICAM-1 expression on vascular endothelial cells might be involved in systemic vascular injuries of the generalized Shwartzman reaction, and that it might be regulated by gamma interferon.

Animals↗
PubMed1987

Complement activation and vascular injury in systemic lupus erythematosus.

The deposition of immune complexes within blood vessel walls results in the potential for complement activation and the release of chemotactic factors, such as fragments of C5 (C5fr). The generation of C5fr results in the intravascular aggregation of neutrophils with subsequent leukostatic occlusion of the pulmonary arterioles. The generation of C5fr may contribute to the pathogenesis of adult respiratory distress syndrome and other diseases. Studies were undertaken to determine the role of circulating complement derived peptides and intravascular neutrophil activation in systemic lupus erythematosus.

Antigen-Antibody Complex↗
PubMed1989

Local skin burn causes systemic (lung and kidney) endothelial cell injury reflected by increased circulating and decreased tissue factor VIII-related antigen.

Inasmuch as xanthine oxidase (XO)-derived O2* metabolites may contribute to vascular endothelial injury and Factor VIII antigen (F8Ag) is a component of endothelial cells, we hypothesized that XO-derived O2* might damage and cause distant organ endothelial cells to release F8Ag in rats subjected to skin burn. We found that serum F8Ag (ELISA) increased in the blood of rats subjected to skin burn (70 degrees C water to shaved dorsal skin for 30 seconds) but not in sham control rats (30 degrees C water). Coincidentally, F8Ag levels also decreased in lung and kidney tissue sections (immunofluorescent staining) of burned rats but not sham rats. Increases in circulating F8Ag levels and decreases in tissue F8Ag levels appeared to result from XO-derived O2* metabolites: F8Ag levels did not increase in the blood and did not decrease in the tissues of rats pretreated with allopurinol (a specific XO inhibitor, 50 mg/kg) or dimethylthiourea (DMTU) (a permeable O2* metabolite scavenger, 250 mg/kg). Lung injury as assessed by permeability studies (I125-albumin leak) paralleled changes in blood F8Ag levels in sham, burn, allopurinol-, and DMTU-treated groups. We conclude that skin burn causes a systemic vascular injury that can be inhibited by allopurinol or DMTU and is reflected by increased circulating and tissue decreased Factor VIII antigen levels. Release of Factor VIII antigen may serve as a valuable marker of distant organ injury in patients with skin burn.

Allopurinol↗
PubMed1988

Kinins induce abnormal vascular reactivity.

Previous studies have shown that after experimental neural trauma or acute hypertension the brain produces superoxide anion radicals, and brain arterioles display endothelial lesions, dilation, and loss of normal reactivity in response to a decrease in CO2 tension. Because these abnormalities are prevented by pretreatment with free radical scavengers or inhibitors of the cyclooxygenase component of prostaglandin (PG) H synthase, arachidonic acid metabolism by PGH synthase with concomitant formation of tissue injuring oxygen radicals causes the vascular damage. The purpose of the present experiments was to determine whether kinins, which are known to stimulate arachidonate metabolism and to induce cerebral arteriolar dilation via production of superoxide anion, may be involved in initiating the cerebrovascular abnormalities produced by neural trauma in cats. The diameter and reactivity of untreated in vivo pial arterioles on one cerebral cortex was compared with the diameter and reactivity of pial arterioles on the contralateral cortex, which were pretreated topically with a competitive receptor antagonist, which is specific for kinins. Before fluid percussion neural trauma was induced, arterioles on both cerebral hemispheres constricted normally to a decrease in CO2 tension. After injury, the arterioles on the untreated cortex dilated and did not constrict in response to a decrease in arterial CO2 tension, whereas the arterioles pretreated with the kinin antagonist dilated less and displayed normal reactivity to CO2. These experiments demonstrate that a specific kinin receptor stimulates PGH synthase-dependent, free radical-mediated cerebrovascular injury. Given the ubiquitous distribution of the kallikrein-kinin system, we propose that kinins may be an important common mediator of systemic vascular injury and abnormal vascular reactivity.

Animals↗
PubMed1992

Claudication induces systemic capillary endothelial swelling.

An in vivo model of intermittent claudication has been developed to investigate systemic reperfusion injury associated with transient muscle ischaemia. Rats were subjected to unilateral common iliac artery ligation and two weeks of intermittent hind limb muscle stimulation. Electron microscopy demonstrated a significantly increased percentage of swollen capillary endothelial cells both locally and systemically in these "claudicant" rats, compared with controls or those undergoing muscle stimulation or artery ligation alone. These results support human data suggesting that claudication induces an inflammatory response which results in systemic vascular injury.

Animals↗
PubMed1989

Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) react with constituents of neutrophil primary granules and monocyte lysosomes. Indirect immunofluorescence microscopy using alcohol-fixed neutrophils demonstrates two ANCA types: one causing cytoplasmic staining (C-ANCA), and a second causing artifactual perinuclear staining (P-ANCA) that frequently has specificity for myeloperoxidase. Using indirect immunofluorescence microscopy (IIFM) and enzyme immunoassays (EIA), sera from over 300 patients with renal disease, with and without systemic vasculitis, were analyzed. Of 76 patients with pauci-immune glomerulonephritis with crescents or necrosis, 87% had ANCA by IIFM (38% of C-ANCA type, 49% of P-ANCA type), and 78% had ANCA by EIA. Of 55 patients with nonlupus immune complex-mediated glomerulonephritis, only 11% had ANCA by IIFM and 5% had ANCA by EIA. Of 24 patients with anti-GBM antibody-mediated glomerulonephritis, none had ANCA. Renal and extrarenal lesions were studied in 81 patients with ANCA-associated glomerulonephritis. These patients formed a pathologic continuum ranging from renal-limited to widespread systemic vascular injury, including patients with primary crescentic glomerulonephritis, Wegener's granulomatosis, and polyarteritis nodosa. In ANCA-positive patients the frequency of C-ANCA and P-ANCA correlated with disease distribution. P-ANCA was most frequent with renal-limited disease and C-ANCA was most frequent when there was lung and sinus involvement. It is proposed that ANCA are not only useful diagnostic markers, but may also be directly involved in a novel pathogenetic mechanism that is a frequent cause of crescentic glomerulonephritis and systemic necrotizing vasculitis.

Adolescent↗
PubMed1996

The somatostatin analog angiopeptin does not reduce chronic hypoxic pulmonary hypertension in rats.

Angiopeptin is an analog of somatostatin-14, which has been found to inhibit cellular proliferation in several models of systemic vascular injury. As proliferation plays a major role in pulmonary hypertension, we examined the hypothesis that angiopeptin would inhibit the development of chronic hypoxic pulmonary hypertension in the rat. Angiopeptin was infused intravenously (90-100 microg/kg/day) by minipumps in 10 rats during a 3-week exposure to hypobaric hypoxia and in six normoxic rats. Normal saline was infused in six hypoxic control rats and in seven normoxic control rats. Angiopeptin produced no significant difference in mean pulmonary arterial pressure and resistance, right ventricular weight, or medial thickness of small pulmonary vessels. Vasoconstrictor responses of isolated lungs to acute hypoxia were not affected by angiopeptin. We conclude that angiopeptin, at the high intravenous dose used, does not significantly reduce the development of chronic hypoxic pulmonary hypertension in rats.

Animals↗