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PubMed2005

Persistent endothelial dysfunction is related to elevated C-reactive protein (CRP) levels in Type II diabetic patients after acute myocardial infarction.

The atherosclerotic process is an ongoing dynamic and progressive state arising from endothelial dysfunction and inflammation. Although suffering from an acute coronary artery disease, patients with Type II diabetes have a poor outcome compared with non-diabetic patients, which may only partly be explained by traditional risk factors. Our purpose was to compare non-traditional risk factors, such as endothelial function, C-reactive protein (CRP) and adiponectin, in Type II diabetic and non-diabetic patients following AMI (acute myocardial infarction). Twenty Type II diabetic patients were compared with 25 non-diabetic patients at baseline (1-3 days from the onset of chest pain) and at 60 days follow-up after an AMI. Using high-resolution ultrasound, brachial artery responses to FMD (flow-mediated vasodilatation; endothelium-dependent vasodilatation) and NTG (nitroglycerine-induced vasodilatation; endothelium-independent vasodilatation) were measured. Plasma levels of CRP and adiponectin were measured by ELISA. At baseline, FMD (1.9 compared with 3.2%; P=0.22) and CRP levels (6.95 compared with. 5.51 mg/l; P=0.40) did not differ between Type II diabetic and non-diabetic patients, whereas adiponectin levels were lower in Type II diabetic patients (2.8 compared with 5.0 ng/ml; P<0.05). At 60 days follow-up, there were significant differences in FMD (1.5 compared with 4.1%; P<0.02), CRP (4.23 compared with 1.46 mg/ml; P<0.01) and adiponectin (3.3 compared with 5.3 ng/ml; P<0.05) levels between Type II diabetic and non-diabetic patients. In contrast, NTG responses improved in both groups between baseline and follow-up (Type II diabetic patients, 9.7 compared with 13.2% respectively, P<0.05; non-diabetic patients, 7.9 compared with 12.4% respectively, P<0.01). These results show a persistent endothelium-dependent dysfunction and inflammatory activity in patients with Type II diabetes, but not in non-diabetic patients, after AMI. These findings may, in part explain, the poor outcome in coronary artery disease seen in Type II diabetes.

Adiponectin↗

PubMed1996

Macro-microangiopathy and endothelial dysfunction in NIDDM patients with and without diabetic nephropathy.

The Steno hypothesis suggests that albuminuria reflects widespread vascular damage (proliferative retinopathy and severe macroangiopathy) due to a generalized vascular (endothelial) dysfunction. We assessed this concept in NIDDM (non-insulin-dependent diabetic) patients with (13 female/ 39 male, age 60 +/- 7 years, group 1) and without (12 female /41 male, age 61 +/- 7 years, group 2) diabetic nephropathy compared to matched non-diabetic subjects (7 female/15 male, age 58 +/- 8 years, group 3). A 12-lead ECG was recorded and coded blindly using the Minnesota Rating Scale; the World Health Organization cardiovascular questionnaire was used to assess past and present evidence of myocardial infarction, angina pectoris, stroke, and peripheral vascular disease (digital systolic blood pressure determination). The degree of diabetic retinopathy was scored from fundus photography. The following variables were measured: transcapillary escape rate of albumin (initial disappearance of intravenously injected 125I-labelled human serum albumin), plasma concentrations of prorenin (radioimmunoassay) and serum concentrations of von Willebrand factor (enzyme-linked immunoadsorbent assay). Prevalence of ischaemic heart disease (ECG reading) (49/20/5)% and peripheral vascular disease as indicated by reduced systolic blood pressure on big toe (69/30/ 14)% was significantly higher in group 1 vs group 2 (p < 0.01) and in group 2 vs group 3 (p < 0.01), respectively. The prevalence and severity of retinopathy was higher in group 1 vs 2 (p < 0.01). Transcapillary escape rate of albumin (%/h) was elevated in group 1 and 2 as compared to control subjects: 7.9 (4.3-13.7); 7.4 (3.7-16.4) vs 6.0 (3.4-8.7), (p < 0.005), respectively. Plasma prorenin activity (IU/ml) was raised in group 1 and group 2 as compared to group 3: 272 (59-2405); 192 (18-813), and 85 (28-246), p < 0.001, respectively. Serum von Willebrand factor (IU/ ml) was elevated in group 1 as compared to group 2 and 3: 2.07 (0.83-4.34); 1.60 (0.30-2.99) and 1.50 (1.00-2.38), p < 0.001, respectively. Our study demonstrated that NIDDM patients with and without albuminuria had increased transcapillary escape of albumin and raised prorenin activity, whereas only those with albuminuria had increased von Willebrand factor. Patients with NIDDM may have abnormal endothelial function in the absence of albuminuria.

Aged↗

PubMed1999

Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity.

OBJECTIVE: To ascertain in obesity the role of body fat distribution (the strongest predictor of morbility and mortality in obese subjects) in determining the degree of endothelial dysfunction, an early marker of atherosclerotic disease. SUBJECTS: 18 premenopausal women with uncomplicated obesity excluding other cardiovascular risk factors and 12 age-matched slim healthy women. MEASUREMENTS: Endothelium-dependent vasodilation, studied as diameter variation in response to an increase in shear-stress, was evaluated in the right common femoral artery of obese and slim subjects by a non invasive approach and compared to glyceril-trinitrate vasodilation. To characterize better the vascular functional and/or structural properties, we studied the arterial wall distensibility by an echo-tracking system. Adipose tissue regional distribution was determined by computerised axial tomography. RESULTS: The endothelium-dependent vasodilation was significantly impaired in obese subjects (P<0.005 versus non-obese subjects) while glyceril-trinitrate vasodilation and arterial distensibility were similar in the two groups. In our obese subjects endothelial-dependent vasodilation was inversely correlated to body fat distribution (visceral/subcutaneous adipose tissue ratio: r=- 0. 624, P=0.0058). In contrast, metabolic parameters (except C-peptide response during oral glucose tolerance test (OGTT): r=-0.587, P=0. 01), blood pressure values and body weight did not correlate with the endothelial function. CONCLUSION: Uncomplicated obesity per se is characterised by an alteration of the endothelial function; the degree of this vascular damage is predicted by body fat distribution independently of body weight and metabolic and other haemodynamic parameters, and correlates with an index of insulin secretion.

Adipose Tissue↗

PubMedDate not supplied

No evidence of endothelial dysfunction in patients with Alzheimer's disease.

In view of accumulating evidence of vascular pathology in Alzheimer's disease (AD), we tested the hypothesis that AD patients have impaired endothelial function. This was assessed using the technique of strain-gauge venous occlusion plethysmography, which measures forearm blood flow (FBF). Intra-arterial (brachial) infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) was used to assess local endothelial dependent and independent responses, respectively. There was no difference in the basal FBF of patients and controls. ACh and SNP caused dose-related increases in FBF from baseline, but no difference was recorded between the AD and control group. This study provides no evidence of endothelial dysfunction in the systemic circulation of patients with AD.

Acetylcholine↗

PubMed2002

Asymmetric dimethylarginine (ADMA): a potential link between endothelial dysfunction and cardiovascular diseases in insulin resistance syndrome?

Endothelium-derived nitric oxide plays a major role in the regulation of vascular tone and in the maintenance of vascular homeostasis. Endothelial dysfunction with impaired nitric oxide biosynthesis and decreased bioavailability has been implicated in insulin resistance syndrome and Type II (non-insulin-dependent) diabetes mellitus. Nitric oxide is synthesised by nitric oxide synthase. Asymmetric dimethylarginine is a major endogenous nitric oxide synthase inhibitor. Increased circulating asymmetric dimethylarginine was initially found in patients with chronic renal failure and subsequently many other disease states. Increased asymmetric dimethylarginine plasma concentrations could contribute to the development of insulin resistance and coronary heart disease. Understanding of the pathophysiological role of asymmetric dimethylarginine could lead to novel therapies in the prevention of arteriosclerosis and coronary heart disease.

Animals↗

PubMed2002

Prognostic value of coronary vascular endothelial dysfunction.

BACKGROUND: Whether patients at increased risk can be identified from a relatively low-risk population by coronary vascular function testing remains unknown. We investigated the relationship between coronary endothelial function and the occurrence of acute unpredictable cardiovascular events (cardiovascular death, myocardial infarction, stroke, and unstable angina) in patients with and without coronary atherosclerosis (CAD). METHODS AND RESULTS: We measured the change in coronary vascular resistance (DeltaCVR) and epicardial diameter with intracoronary acetylcholine (ACh, 15 micro g/min) to test endothelium-dependent function and sodium nitroprusside (20 micro g/min) and adenosine (2.2 mg/min) to test endothelium-independent vascular function in 308 patients undergoing cardiac catheterization (132 with and 176 without CAD). Patients underwent clinical follow-up for a mean of 46+/-3 months. Acute vascular events occurred in 35 patients. After multivariate analysis that included CAD and conventional risk factors for atherosclerosis, DeltaCVR with ACh (P=0.02) and epicardial constriction with ACh (P=0.003), together with increasing age, CAD, and body mass index, were independent predictors of adverse events. Thus, patients in the tertile with the best microvascular responses with ACh and those with epicardial dilation with ACh had improved survival by Kaplan-Meier analyses in the total population, as did those in the subset without CAD. Similar improvement in survival was also observed when all adverse events, including revascularization, were considered. Endothelium-independent responses were not predictive of outcome. CONCLUSIONS: Epicardial and microvascular coronary endothelial dysfunction independently predict acute cardiovascular events in patients with and without CAD, providing both functional and prognostic information that complements angiographic and risk factor assessment.

Angina, Unstable↗

PubMed2004

Lipoprotein remnants and endothelial dysfunction in the postprandial phase.

The objective of this work was to study whether changes in remnant lipoprotein (RLP) plasma levels during the postprandial phase relate to alterations of the endothelial function. Fasted patients (15 moderately dyslipidemic men) were given an oral fat load (OFL), and blood samples were collected before the OFL ingestion (T0) and 2, 4, 6, and 8 h (T2, T4, T6, T8) thereafter. Endothelial function, determined as flow-mediated dilatation (FMD) of the brachial artery, was assessed at the same time points. Triglyceridemia peaked between T4 (5.48 +/- 0.64 mmol/liter) and T6 (5.34 +/- 0.89 mmol/liter) and decreased at 8 h (4.36 +/- 0.87 mmol/liter) after the OFL. FMD decreased significantly 6 h after the OFL consumption (from 16.03 +/- 1.32% to 11.53 +/- 1.42%, P < 0.01). Cholesterol in RLPs increased steadily up to 6 h and decreased at 8 h (T0 0.53 +/- 0.10, T6 0.81 +/- 0.11, T8 0.73 +/- 0.13 mmol/liter). Fasting levels of triglycerides and cholesterol-RLPs (C-RLPs) correlated significantly with FMD at baseline. The decrease in endothelial function at 6 h also significantly correlated with the area under the curve of triglycerides (R = 0.53, P = 0.04). Postprandial C-RLPs (area under the curve), however, showed the best correlation with the decrease of FMD (R = 0.63, P = 0.012). The correlation persisted in a multivariate analysis. We concluded that C-RLPs contribute significantly to the endothelial dysfunction occurring during the postprandial lipemia.

Adult↗

PubMed2005

[Decrease of nitric oxide (NO)-cGMP-dependent vasodilatation in the vessels of lesser circulation in endothelial dysfunction].

Inducible NO-synthase inhibitor aminoguanidine (AG) was used for investigation into enhanced nitric oxide (NO) production influence on elevated pressure in the pulmonary circulation (pulmonary hypertension, PH) under endothelial dysfunction. PH was simulated by subcutaneous injection of 60 mg/kg MCT to Wistar rats. Experimental groups were given AG in drinking water (15 mg/(kg x day)), and control groups were given drinking water. Rate of nitrite/nitrate excretion (RENOx) with urine was measured. The RENOx was elevated since second week as long as through the PH development. Chronic AG administration led to RENOx and soluble guanylate cyclase (sGC) NO-dependent activity restoration, and also it led to partial restoration of the right ventricular pressure. AG administration restored the perfusion pressure responses of isolated pulmonary arteries to acetylcholine. These results suggest that chronic inducible NO-synthase inhibition restores the impaired endothelium-dependent and sGC-dependent relaxation of pulmonary artery in MC-induced PH.

Animals↗

PubMed2006

[Pulmonary hypertension, endothelial dysfunction, and their correction with lisinopril in patients with heart failure in combination of ischemic heart disease and chronic obstructive pulmonary disease].

The paper contains review of the role of endothelial dysfunction in heart failure in patients with combination of ischemic heart disease and chronic obstructive pulmonary disease and discussion of results of a study in which it was established that lisinopril (10 mg/day) caused attenuation of pulmonary hypertension, improvement of right ventricular systolic function and diastolic ventricular filling at the background of correction of vascular tone.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension.

BACKGROUND: Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. METHODS: The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D-dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). RESULTS: Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =. 012), tPA antigen (P =.0001), fibrinogen (P =.0002), D-dimer (P =. 0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. CONCLUSIONS: Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension.

Blood Coagulation↗

PubMedDate not supplied

The renin angiotensin system and endothelial dysfunction in chronic heart failure: role of endogenous fibrinolysis.

Regulation of vascular tone by the endothelium is abnormal in patients with heart failure and contributes to the characteristic peripheral vasoconstriction and increased afterload. This endothelial dysfunction is mediated through several endothelium-derived factors, including nitric oxide; there is an important interplay between the endothelium and the renin angiotensin system. The benefits of ACE inhibition in heart failure relate, in part, to a reduction in ischemic events which may be mediated by improvements in endothelial function and the endothelium derived fibrinolytic parameters: tissue plasminogen activator (t-PA) and its inhibitor, plasminogen activator inhibitor type 1 (PAI-1). In addition to potential improvements in the regulation of vasomotion, ACE inhibitor therapy may increase bradykinin induced t-PA release and/or reduce angiotensin II mediated PAI-1 release. Recent evidence suggests that both angiotensin II type 1 receptor (AT(1)) antagonism and ACE inhibition improve basal fibrinolytic parameters in patients with heart failure which may facilitate the acute endogenous fibrinolytic response. 1999 by CHF, Inc.

Journal Article↗

PubMed2004

A novel apoA-I mutation (L178P) leads to endothelial dysfunction, increased arterial wall thickness, and premature coronary artery disease.

OBJECTIVES: We investigated the consequences of an apolipoprotein A-I (apoA-I) gene defect with regard to lipid metabolism, endothelial function, arterial wall thickness, and coronary artery disease (CAD) risk. BACKGROUND: Due to limited numbers of carriers of the apoA-I defects, data on the consequences of such defects have remained inconclusive. METHODS: Lipids and lipoproteins were measured in 54 apoA-I (L178P) carriers and 147 nonaffected siblings. Flow-mediated dilation (FMD) was assessed in 29 carriers and 45 noncarriers, and carotid intima-media thickness (IMT) could be determined in 33 heterozygotes and 40 controls. Moreover, CAD risk was evaluated for all apoA-I mutation carriers. RESULTS: Heterozygotes exhibited lower plasma levels of apoA-I (-50%; p < 0.0001) and high-density lipoprotein cholesterol (-63%; p < 0.0001). In addition, carriers had impaired FMD (p = 0.012) and increased carotid IMT (p < 0.001), whereas multivariate analysis revealed that heterozygotes had a striking 24-fold increase in CAD risk (p = 0.003). CONCLUSIONS: Heterozygosity for a novel apoA-I mutation underlies a detrimental lipoprotein profile that is associated with endothelial dysfunction, accelerated carotid arterial wall thickening, and severely enhanced CAD risk. Importantly, the extent of atherosclerosis in these subjects was similar to the burden of premature arterial wall abnormalities seen in patients with familial hypercholesterolemia. These data illustrate the pivotal role in humans of apoA-I in the protection against CAD.

Adult↗

PubMed2005

Obesity, insulin resistance, and the metabolic syndrome: determinants of endothelial dysfunction in whites and blacks.

BACKGROUND: Insulin resistance is strongly associated with obesity and other components of the metabolic syndrome (MS). The relative importance of these components in the determination of endothelial function is unknown. Furthermore, there is conflicting evidence about whether ethnic differences exist in the relative importance of these components in regard to other cardiovascular outcomes. We evaluated the contributions of insulin resistance, obesity, and the other components of the MS to impaired endothelial function. METHODS AND RESULTS: The relationships of the MS components (as defined according the National Cholesterol Education Program) and insulin resistance (estimated using the homeostasis model) with endothelium-dependent vasodilation were examined in 42 white and 55 black subjects. Endothelium-dependent vasodilation was assessed as the increment in leg blood flow (measured by thermodilution) after exposure to methacholine chloride. Waist circumference, glucose, blood pressure, and insulin resistance distributions did not differ between ethnic groups; blacks in our sample had higher HDL cholesterol (1.31 versus 1.09 mmol/L; P<0.001) and lower triglyceride levels (1.01 versus 1.37 mmol/L; P=0.005) than white subjects. In the absence of the MS, black subjects exhibited reduced endothelium-dependent vasodilation compared with white subjects (P=0.005), and both groups demonstrated significantly worse endothelial function when the MS was present (maximal increase in leg blood flow: blacks: 107+/-9% MS absent, 53+/-16% MS present; whites: 163+/-16% MS absent, 54+/-18% MS absent; P=0.007, MS absent versus present; P=NS for interaction of ethnicity and MS). Multivariable regression analysis examining relationships of endothelial function with the 5 MS components (analyzed as continuous variables) revealed independent relationships only with waist circumference (P=0.01) and systolic blood pressure (P=0.02). Waist circumference was no longer independently associated after adding insulin resistance to the modeling (P=0.02 for log of homeostasis model index of insulin resistance, P=0.02 for systolic blood pressure). Ethnicity still exerted an independent effect on endothelial function after accounting for the above components (P=0.04 for an additional effect of ethnic status on endothelial function), with an ethnic difference in the effect of insulin resistance on endothelial function (P=0.046 for interaction of ethnicity and log of homeostasis model index of insulin resistance). CONCLUSIONS: These findings suggest that insulin resistance and systolic blood pressure are the principal determinants of endothelial dysfunction in the MS and that there are ethnic differences in the relative importance of these factors. These differences may imply different benefits from treatments targeting blood pressure or insulin resistance in different ethnic groups.

Adult↗

PubMed2002

Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction.

BACKGROUND: The functional changes associated with cellular senescence may be involved in human aging and age-related vascular disorders. We have shown the important role of telomere and telomerase in vascular cell senescence in vitro. Progressive telomere shortening in vivo has been observed in the regions susceptible to atherosclerosis, implying contributions to atherogenesis. However, whether senescent vascular cells are present in the vasculature and contribute to the pathogenesis of atherosclerosis remains unclear. METHODS AND RESULTS: Senescence-associated beta-galactosidase (beta-gal) activity was examined in the coronary arteries and the internal mammary arteries retrieved from autopsied individuals who had had ischemic heart diseases. Strong beta-gal stainings were observed in atherosclerotic lesions of the coronary arteries but not in the internal mammary arteries. An immunohistochemical analysis using anti-factor VIII antibody demonstrated that beta-gal stained cells are vascular endothelial cells. To determine whether endothelial cell senescence causes endothelial dysfunction, we induced senescence in human aortic endothelial cells (HAECs) by inhibiting telomere function and examined the expression of intercellular adhesion molecule (ICAM)-1 and endothelial nitric oxide synthase (eNOS) activity. Senescent HAECs exhibited increased ICAM-1 expression and decreased eNOS activity, both of which are alterations implicated in atherogenesis. In contrast, introduction of telomerase catalytic component significantly extended the life span and inhibited the functional alterations associated with senescence in HAECs. CONCLUSIONS: Vascular endothelial cells with senescence-associated phenotypes are present in human atherosclerotic lesions, and endothelial cell senescence induced by telomere shortening may contribute to atherogenesis.

Cells, Cultured↗

PubMed2003

[Endothelial cell senescence in human atherosclerosis: role of telomeres in endothelial dysfunction].

BACKGROUND: The functional changes associated with cellular senescence may be involved in human aging and age-related vascular disorders. We have shown the important role of telomeres and telomerase in vascular cell senescence in vitro. Progressive telomere shortening in vivo has been observed in the regions susceptible to atherosclerosis, implicating its contributions to atherogenesis. However, whether senescent vascular cells are present in the vascularture and contribute to the pathogenesis of atherosclerosis remains unclear. METHODS AND RESULTS: Senescence-associated beta-galactosidase (beta-gal) activity was examined in the coronary arteries and the internal mammary arteries retrieved from autopsied individuals who had ischemic heart diseases. Strong beta-gal staining was observed in atherosclerotic lesions of the coronary arteries but not in the internal mammary arteries. An immunohistochemical analysis using anti-factor VIII antibody demonstrated that beta-gal stained cells are vascular endothelial cells. To determine whether endothelial cell senescence causes endothelial dysfunction, we induced senescence in human aortic endothelial cells (HAECs) by inhibiting telomere function and examined the expression of intercellular adhesion molecule (ICAM)-1 and endothelial nitric oxide synthase (NOS) activity. Senescent HAECs exhibited increased ICAM-1 expression and decreased eNOS activity, both of which are alterations implicated in atherogenesis. In contrast, introduction of telomerase catalytic component significantly extended the life span and inhibited the functional alterations associated with senescence in HAECs. CONCLUSIONS: Vascular endothelial cells with senescence-associated phenotypes are present in human atherosclerotic lesions, and endothelial cell senescence induced by telomere shortening may contribute to atherogenesis.

Aging↗

PubMed2001

Endothelial dysfunction in endocrine disease.

In addition to diabetes mellitus and obesity, acromegaly, Cushing's syndrome, hypopituitarism, hypo- and hyperthyroidism, hyperparathyroidism and polycystic ovary syndrome are associated with either increased mortality from, or increased prevalence of, cardiovascular disease (CVD). Recently, endothelial dysfunction has been identified as an early marker of CVD and has been shown to predict future coronary artery disease, before atherosclerotic changes appear in arteries. Thus, measurement of endothelial function might identify at-risk individuals early and be a useful means of assessing response to treatment aimed at reducing long-term morbidity and/or mortality from CVD. Such studies are being undertaken in hypopituitarism and other endocrinopathies, and are reviewed herein. Endothelial function in large vessels can be measured noninvasively by ultrasound measurement of flow-mediated endothelium-dependent dilation (FMD). Serum markers of endothelial function, such as von Willebrand's factor, thrombomodulin, E-selectin and intercellular adhesion molecule 1, could be increased and be useful for evaluation of treatment, because they correlate inversely with FMD.

Acromegaly↗

PubMed1999

Elevated serum TNF-alpha level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients.

AIMS: The aim of the study was to analyse the role of tumour necrosis factor-alpha (TNF-alpha) in insulin resistance and endothelial dysfunction in patients with different types of obesity. PATIENTS AND METHODS: Fasting serum TNF-alpha immunoreactive concentration (enzyme-linked immunosorbent assay, ELISA) and bioactivity (L929 cell cytotoxicity assay), endothelin-1 and C-peptide levels (radioimmunoassay, RIA) were measured in 15 patients with android- and 13 patients with gynoid-type obesity and 15 lean healthy controls with normal glucose tolerance and blood pressure. RESULTS: Significantly (P<0.01) higher TNF-alpha concentration (8.92 +/- 0.44 pg/ml) and bioactivity (3.12 +/- 0.48 U/ml) were found in patients with android obesity as compared to patients with gynoid obesity (7.01 +/- 0.30 pg/ml, 0.97 +/- 0.11 U/ml) and to the lean controls (6.88 +/- 0.26 pg/ml, 0.88 +/- 0.08 U/ml). Serum endothelin-1 (5.38 +/- 0.30 pg/ml) and C-peptide levels (4.82 +/- 0.71 ng/ml) were also significantly higher (P < 0.01) in patients with android-type obesity than in controls (3.89 +/- 0.43 pg/ml, 1.46 +/- 0.25 ng/ml, respectively). In patients with gynoid-type obesity, only the C-peptide levels proved to be significantly higher (2.84 +/- 0.29 ng/ ml). Endothelin-1 levels, although were found to be slightly higher, did not differ statistically from in controls (4.56 +/- 0.31 pg/ml). There were significant positive linear correlations only in patients with android-type obesity between TNF-alpha, body mass index (BMI), serum endothelin-1 and C-peptide levels. CONCLUSIONS: TNF-alpha may be one of the factors contributing to insulin resistance and vascular dysfunction in patients with android obesity.

Adult↗

PubMed1983

Pulmonary endothelial dysfunction in the presence or absence of interstitial injury induced by intratracheally injected bleomycin in rabbits.

Previously, we reported that repeated subcutaneous administration of bleomycin (BLM) to rabbits produced functional and structural endothelial damage with no evidence of interstitial fibrosis. In the present study, rabbits received intratracheally a single injection of BLM (6 units/kg, n = 6: "low dose" or 11 units/kg, n = 4: "high dose"); 6 additional animals received intratracheally an injection of saline and served as controls. Four weeks after BLM administration, the low-dose group demonstrated significant reduction in the single-pass pulmonary removal of 14C-5-hydroxytryptamine (5-HT) (p less than 0.05; n = 4), whereas 3H-norepinephrine (NE) removal and 3H-benzoyl-phe-ala-pro (BPAP) substrate for lung angiotensin converting enzyme (ACE) metabolism in vivo, as well as lung and serum ACE activity in vitro remained at control levels. No morphologic or biochemical evidence of fibrosis was observed. In contrast, the high-dose BLM group exhibited significant reductions in 14C-5-HT and 3H-NE removal and 3H-BPAP metabolism in vivo, but no significant changes in lung or serum ACE activity in vitro. Furthermore, there was evidence of fibrosis, as revealed by a 59% increase in lung hydroxyproline content and by light microscopic examination of lung tissue. We conclude that intratracheal administration of BLM to rabbits can produce endothelial dysfunction in the presence or absence of interstitial injury.

Animals↗