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1.
Thromb Res ; 117(3): 271-7, 2006.
Article in English | MEDLINE | ID: mdl-15890390

ABSTRACT

INTRODUCTION: Thrombomodulin (TM) has been described as a marker of endothelial injury in atherosclerosis. The role of TM as a predictor of PAD severity is to be proven. The goal of the present study is to compare the level of plasmatic (TMp) in patients with intermittent claudication with patients with critical ischemia in the lower limbs. MATERIALS AND METHODS: TMp was measured using ELISA in the plasma of 41 patients with intermittent claudication degree 1 and in 40 patients presenting critical ischemia in the lower limbs degrees 2 and 3, according to TASC. The hypotheses of normality and homogeneity of the variance had been proven via Shapiro-Wilk and Levene tests, respectively. The comparison of the TMp between the groups was done using the t-Student test. RESULTS: No statistically significant difference was observed. The average levels of TMp for intermittent claudication were 5.2 ng/ml (0.78-13.61 ng/ml) and TMp for critical ischemia in the lower limbs were 6.34 (0.82-18.22 ng/ml) where p=0.265. CONCLUSION: TMp does not seem to be an appropriate marker for PAD severity.


Subject(s)
Endothelium, Vascular/pathology , Intermittent Claudication/pathology , Ischemia/pathology , Thrombomodulin/blood , Aged , Arterial Occlusive Diseases/pathology , Atherosclerosis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Inflammation , Male , Middle Aged , Models, Statistical , Reproducibility of Results , Time Factors
2.
Braz J Med Biol Res ; 36(4): 491-4, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12700827

ABSTRACT

Hormone replacement therapy (HRT) reduces cardiovascular risks, although the initiation of therapy may be associated with transient adverse ischemic and thrombotic events. Antibodies against heat shock protein (Hsp) and oxidized low density lipoprotein (LDL) have been found in atherosclerotic lesions and plasma of patients with coronary artery disease and may play an important role in the pathogenesis of atherosclerosis. The aim of the present study was to assess the effects of HRT on the immune response by measuring plasma levels of antibodies against Hsp 65 and LDL with a low and high degree of copper-mediated oxidative modification of 20 postmenopausal women before and 90 days after receiving orally 0.625 mg equine conjugate estrogen plus 2.5 mg medroxyprogesterone acetate per day. HRT significantly increased antibodies against Hsp 65 (0.316 +/- 0.03 vs 0.558 +/- 0.11) and against LDL with a low degree of oxidative modification (0.100 +/- 0.01 vs 0.217 +/- 0.02) (P<0.05 and P<0.001, respectively, ANOVA). The hormone-mediated immune response may trigger an inflammatory response within the vessel wall and potentially increase plaque burden. Whether or not this immune response is temporary or sustained and deleterious requires further investigation.


Subject(s)
Autoantibodies/blood , Bacterial Proteins , Chaperonins/immunology , Hormone Replacement Therapy , Lipoproteins, LDL/immunology , Medroxyprogesterone Acetate/therapeutic use , Postmenopause/immunology , Progesterone Congeners/therapeutic use , Aged , Analysis of Variance , Autoantibodies/drug effects , Chaperonin 60 , Female , Humans , Middle Aged , Postmenopause/drug effects
3.
Braz. j. med. biol. res ; 36(4): 491-494, Apr. 2003. ilus, tab
Article in English | LILACS | ID: lil-331225

ABSTRACT

Hormone replacement therapy (HRT) reduces cardiovascular risks, although the initiation of therapy may be associated with transient adverse ischemic and thrombotic events. Antibodies against heat shock protein (Hsp) and oxidized low density lipoprotein (LDL) have been found in atherosclerotic lesions and plasma of patients with coronary artery disease and may play an important role in the pathogenesis of atherosclerosis. The aim of the present study was to assess the effects of HRT on the immune response by measuring plasma levels of antibodies against Hsp 65 and LDL with a low and high degree of copper-mediated oxidative modification of 20 postmenopausal women before and 90 days after receiving orally 0.625 mg equine conjugate estrogen plus 2.5 mg medroxyprogesterone acetate per day. HRT significantly increased antibodies against Hsp 65 (0.316 ± 0.03 vs 0.558 ± 0.11) and against LDL with a low degree of oxidative modification (0.100 ± 0.01 vs 0.217 ± 0.02) (P<0.05 and P<0.001, respectively, ANOVA). The hormone-mediated immune response may trigger an inflammatory response within the vessel wall and potentially increase plaque burden. Whether or not this immune response is temporary or sustained and deleterious requires further investigation


Subject(s)
Humans , Female , Middle Aged , Autoantibodies , Heat-Shock Proteins , Hormone Replacement Therapy , Lipoproteins, LDL , Medroxyprogesterone Acetate , Postmenopause , Analysis of Variance , Autoantibodies , Postmenopause
4.
J Lipid Res ; 37(12): 2510-24, 1996 Dec.
Article in English | MEDLINE | ID: mdl-9017504

ABSTRACT

Several studies have demonstrated that lipid-free apolipoproteins can promote cholesterol and phospholipid efflux from cells; however, the mechanisms and the role of cell-mediated pathways involved remain incompletely elucidated. We have recently demonstrated that brefeldin A or monensin, agents that disrupt Golgi apparatus structure and function, inhibit intracellular cholesterol efflux from cells to high density lipoproteins. In the present study we examined the effects of those agents on cell cholesterol and phospholipid efflux to purified apolipoprotein A-I (apoA-I) and apolipoprotein-depleted acceptors from cholesterol-loaded fibroblasts. Brefeldin A or monensin treatment of cells during incubation with apoA-I inhibited efflux of cellular cholesterol by greater than 80% compared with control cells, measured by changes in cellular cholesterol radioactivity, mass, and the substrate pool of cholesterol available for esterification by acyl coenzyme A:cholesterol acyltransferase. Inhibition of cholesterol efflux by these agents could not be overcome by increasing the apoA-I concentration and persisted during incubations up to 24 h. Similarly, brefeldin A and monensin inhibited up to 80% of apoA-I-mediated efflux of labeled phospholipids from cholesterol-loaded cells relative to controls. In contrast, lipid efflux mediated by apolipoprotein-depleted acceptors (trypsin-modified HDL and sonicated phospholipid vesicles) was not sensitive to these drugs. On the basis the known effects of brefeldin A and monensin on Golgi apparatus structure and function, these results are consistent with the notion that efflux of cell lipids by apolipoprotein-dependent mechanisms, but not by apolipoprotein-independent mechanisms, require active cellular processes involving an intact and functional Golgi apparatus.


Subject(s)
Apolipoproteins/metabolism , Cholesterol/metabolism , Golgi Apparatus/metabolism , Phospholipids/metabolism , Biological Transport/drug effects , Brefeldin A , Cyclopentanes/pharmacology , Fibroblasts/metabolism , Fibroblasts/ultrastructure , Golgi Apparatus/drug effects , Humans , Monensin/pharmacology , Protein Synthesis Inhibitors/pharmacology
5.
J Neurochem ; 66(6): 2429-35, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8632166

ABSTRACT

Inheritance of the epsilon 4 allele of apolipoprotein (apo) E is associated with increased risk of Alzheimer's disease (AD) and with increased beta-amyloid peptide (A beta) deposition in the cortex. Apo E is a member of a family of exchangeable apos, characterized by the presence of amphipathic alpha-helical segments that allow these molecules to act as surfactants on the surface of lipoprotein particles. Two members of this family, apo E and apo J, have been shown to bind soluble A beta, and both are associated with senile plaques in the AD cortex. We now have studied the pattern of brain apo expression and found that five members of this class are present: apo A-I, A-IV,D,E, and J. By contrast, apos A-II, B, and C-II were not detectable. Immunohistochemistry revealed that, in addition to apo E and apo J, apo A-I immunostained occasional senile plaques in AD cortex. Immunoblot analysis showed no difference in the relative amounts of any of these apos in tissue homogenates of frontal lobe from AD or control patients. Comparison by APO E genotype showed no differences in the amount of apo E in brain among APO E epsilon 3/3, epsilon 3/4, or epsilon 4/4 individuals; however, a significant decrease in the amount of apo J was associated with the APO E epsilon 4 allele. No differences in apo J levels were detected in CSF samples of AD subjects. We propose that several members of the exchangeable apo family may interact with A beta deposits in senile plaques through common amphipathic alpha-helical domains. Competition among these molecules for binding of A beta or A beta aggregates may influence the deposition of A beta in senile plaques.


Subject(s)
Alzheimer Disease/metabolism , Apolipoproteins/biosynthesis , Molecular Chaperones , Aged , Aged, 80 and over , Alzheimer Disease/physiopathology , Apolipoprotein A-I/analysis , Apolipoprotein A-I/biosynthesis , Apolipoproteins/analysis , Apolipoproteins E/analysis , Apolipoproteins E/biosynthesis , Brain Chemistry/genetics , Brain Chemistry/physiology , Clusterin , Glycoproteins/analysis , Glycoproteins/biosynthesis , Humans , Immunoblotting , Immunohistochemistry , Middle Aged
6.
Circulation ; 83(5): 1705-15, 1991 May.
Article in English | MEDLINE | ID: mdl-1850666

ABSTRACT

BACKGROUND: Active oxygen species can influence vascular tone and platelet activation through a variety of mechanisms. This study assessed the role of the superoxide anion, the hydroxyl radical, and hydrogen peroxide in vasoconstriction and mural thrombosis after coronary artery angioplasty in intact dogs. METHODS AND RESULTS: Injury was induced by inflation of a balloon catheter 50 +/- 6% above baseline arterial diameter; dogs were followed for 2 hours before death. Epicardial coronary diameters at arteriography and extent of thrombus deposition at serial histological sections were analyzed in controls (n = 20) and in dogs pretreated with superoxide dismutase (SOD, a superoxide radical scavenger, n = 10); other dogs were pretreated with the hydrogen peroxide scavenger catalase (n = 8), the iron chelator deferoxamine (n = 6), or the hydroxyl radical scavenger 1,3-dimethyl-2-thiourea (n = 9). Angioplasty-induced injury was similar among groups. After angioplasty, control dogs exhibited localized and persistent vessel constriction, which was maximal at the initial 5 minutes (28.9 +/- 6.3% diameter decrease versus baseline). Corresponding arterial diameters of SOD-treated dogs were 24-69% larger (95% confidence interval, p less than 0.001) than controls at 5 minutes and, on average, 32% larger than controls thereafter (p less than 0.01). Vasoconstriction was not prevented by the other treatments. The SOD dose used accounted for inhibition of zymosan-stimulated blood cytochrome c reduction versus baseline (7 +/- 3 versus 30 +/- 6 nmol/min/10(6) cells, respectively, p = 0.003); such inhibition occurred in no other group. Prevalence of mural thrombosis was similar among all groups, but large thrombi (greater than 15% of lumen area) were absent in SOD-treated dogs, contrary to control group (p = 0.028); other groups were similar to control. In the absence of injury, SOD alone induced no change in coronary diameter, coronary blood flow, or platelet aggregation. CONCLUSIONS: These data provide evidence implicating the superoxide radical in the genesis of vasoconstriction after coronary angioplasty in vivo. Such effects seem to be independent of its conversion to hydroxyl radicals and availability of hydrogen peroxide or catalytic iron complexes.


Subject(s)
Angioplasty, Balloon, Coronary/adverse effects , Coronary Vasospasm/etiology , Superoxides/metabolism , Angiography , Animals , Blood Cell Count , Coronary Circulation/drug effects , Coronary Vasospasm/diagnostic imaging , Coronary Vasospasm/physiopathology , Cytochrome c Group/blood , Dogs , Female , Free Radicals , Heart Diseases/etiology , Hemodynamics , Male , Microscopy, Electron, Scanning , Oxidation-Reduction , Platelet Aggregation/drug effects , Superoxide Dismutase/pharmacology , Thrombosis/etiology
7.
Braz J Med Biol Res ; 22(7): 913-5, 1989.
Article in English | MEDLINE | ID: mdl-2629957

ABSTRACT

To investigate the cellular reactions to arterial injuries and the influence of a cholesterol-rich diet, 18 rabbits underwent endothelial denudation of the abdominal aorta with a balloon catheter. Fourteen animals were fed a 2% cholesterol diet and 4 were fed normal rabbit chow for 8 weeks. In the cholesterol-fed group, 6 animals had only the expected intimal lesions; however, 8 animals exhibited different degrees of balloon-induced medial layer injury, with fibrous healing. Similarly, in the control rabbits, 1 had intimal lesions and 3 had both intimal and medial layer lesions. We conclude that removal of the endothelium with a balloon catheter promotes arterial wall injury deeper than expected. This unexpected result could influence the effect of interventions usually employed in experimental atherosclerosis.


Subject(s)
Aorta/pathology , Catheterization/adverse effects , Endothelium, Vascular/pathology , Animals , Arteriosclerosis/etiology , Cholesterol/administration & dosage , Diet , Male , Rabbits
8.
Braz. j. med. biol. res ; 22(7): 913-5, 1989. tab
Article in English | LILACS | ID: lil-83375

ABSTRACT

To investigate the cellular reactions to arterial injuries and the influence of a cholesterol-rich diet, 18 rabbits underwent endothelial denudation of the abdominal aorta with a balloon catheter. Fourteen animals were fed a 2% cholesterol diet and 4 were fed normal rabbit chow for 8 weeks. In the cholesterolfed group, 6 animals had only the expected intimal lesions; however, 8 animals exhibited different degrees of balloon=induced medial layer injury, with fibrous healing. Similarly, in the control rabbits, 1 had intimal lesions and 3 had both intimal and medial layer lesions. We conclude that removal of the endothelium with a balloon catheter prometes arterial wall injury deeper than expected. This unexpected result could influence the effect of interventions usually employed in experimental atherosclerosis


Subject(s)
Rabbits , Animals , Male , Aorta/pathology , Catheterization/adverse effects , Endothelium, Vascular/pathology , Arteriosclerosis/etiology , Cholesterol/administration & dosage , Diet
11.
A cardiologia para formação do especialista; (2021), p. 206-221; 1088 p.
in Portuguese | DANTEPAZZANESE, SESSP-IDPCPROD, Sec. Est. Saúde SP, SESSP-IDPCACERVO | ID: dan-4633
12.
Cardiologia condutas terapêuticas; (2018), p. 245-256; 1372 p. : il.
in Portuguese | DANTEPAZZANESE, SESSP-IDPCPROD, Sec. Est. Saúde SP, SESSP-IDPCACERVO | ID: dan-4352
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