M. Candigliota

Universita' degli Studi "Magna Græcia" di Catanzaro, Catanzaro, Calabria, Italy

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Publications (11)46.74 Total impact

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    ABSTRACT: To test whether weight loss may improve endothelial dysfunction in human obesity, we recruited 28 healthy obese subjects, aged 30-46 years, with BMI 30-43 kg/m(2). Endothelium-dependent and -independent vasodilation were investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh; 7.5, 15, and 30 microg x ml(-1) x min(-1)) and sodium nitroprusside (0.8, 1.6, and 3.2 microg x ml(-1) x min(-1)). Insulin resistance was estimated by homeostasis model assessment (HOMA). Weight loss was obtained by caloric restriction and physical activity. We observed a significant reduction in BMI (from 33.1 +/- 4.2 to 27.5 +/- 4.5 kg/m(2), -16.9%, P < 0.0001) and in waist circumference (from 108.2 +/- 12.1 to 96.8 +/- 12.9 cm, -10.5%, P < 0.0001). Weight loss was also associated with a significant increase in ACh-stimulated forearm blood flow (FBF), from 7.4 +/- 2.8 to 12.9 +/- 3.4 ml. 100 ml(-1) of tissue x min(-1) kg/m(2) (P < 0.0001). Multivariate regression analysis demonstrated that the only independent predictor of FBF was HOMA, accounting for 44.5% of the variation, whereas the addition of BMI explained another 2.3% of the variation. Our data demonstrate that energy-restricted diet associated with physical activity induce a significant and clinically relevant improvement in ACh-stimulated vasodilation in obese healthy subjects.
    Diabetes Care 06/2003; 26(6):1673-8. DOI:10.2337/diacare.26.6.1673 · 8.57 Impact Factor
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    ABSTRACT: Reactive oxygen species play a critical role in inducing apoptosis. The small GTPase p21 Ras and the ERK1/2 MAPK have been proposed as key regulators of the signaling cascade triggered by oxidative stress (H2O2). Harvey-Ras (Ha-Ras) and Kirsten-Ras (Ki-Ras) isoforms are so far functionally indistinguishable, because they activate the same downstream effectors, including ERK1/2. Moreover, ERK1/2 signaling has been involved in both protection and induction of apoptosis. Human umbilical vein endothelial cells (HUVECs) were subjected to H2O2, and apoptosis was detected by fluorescence-activated cell sorting analysis, fluorescence microscopy, and caspase-3 activation. Transfection of Ha-Ras and Ki-Ras genes in HUVECs was performed to evaluate the response to H2O2. We have found that, whereas Ha-Ras decreases tolerance to oxidative stress, Ki-Ras has a potent antiapoptotic activity. Both effects are mediated by ERK1/2. Tolerance to H2O2 is encoded by a unique stretch of lysines at the COOH terminus of the Ki-Ras, lacking in Ha-Ras, and it is relatively independent of the farnesylated anchor. Inhibition of p21 Ras signaling by farnesylation inhibitors increased the resistance to apoptosis in Ha-Ras-expressing cells. These findings explain the opposite effects of ERK1/2 stimulation on apoptosis found in different cell types and suggest that local activation of ERK1/2 signaling may account for the opposing response to oxidative stress by Ha-Ras or Ki-Ras-expressing cells. Modulation of cell reactivity to oxidative stress by p21 Ras points to the specific and predictive effects of Ras inhibitors in vivo as potential therapeutic drugs in disorders produced by increase of reactive oxygen species inside the cells.
    Circulation 03/2002; 105(8):968-74. · 14.95 Impact Factor
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    ABSTRACT: Endothelial dysfunction has been reported in obese subjects, but its mechanism has not been elucidated. We have therefore investigated 1) the possible relationship among BMI, waist-to-hip ratio (WHR), and endothelium-dependent vasodilation and 2) whether oxidative stress participates in endothelial dysfunction. We recruited 76 healthy subjects (50 men and 26 women aged 21-45 years) and measured their BMI (kg/m2), WHR, and insulin resistance (IR) estimated by the homeostasis model assessment (HOMA). Endothelium-dependent and -independent vasodilation were assessed by increasing doses of acetylcholine (ACh) (7.5, 15, and 30 pg x ml(-1) x min(-1)) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 microg x ml(-1) x min(-1)) during saline and vitamin C coinfusion (24 mg/min). The effects of cyclooxygenase activity were evaluated by a dose-response curve to intrabrachial coinfusion of ACh and indomethacin (500 microg/min). Three different groups have been identified according to their BMI: group A (BMI <25), consisting of 10 men and 5 women; group B (BMI between 25 and 29), consisting of 16 men and 8 women; and group C (BMI > or =30), consisting of 24 men and 13 women. Obese subjects had significantly lower forearm blood flow (FBF) during ACh infusions (means +/- SD): 19.8 +/- 2.8, 10.8 +/- 2.7, and 6.5 +/- 1.8 ml x 100 ml(-1) tissue x min(-1) (P < 0.0001) for groups A, B, and C, respectively. SNP caused comparable increments in FBF in all groups. Regression analysis revealed a significant negative correlation between BMI (r = -0.676, P < 0.0001), WHR (r = -0.631, P < 0.0001), fasting insulin (r = -0.695, P < 0.0001), HOMA-IR (r = -0.633, P < 0.0001), and percent peak increase in FBF during ACh infusion. In obese subjects, both vitamin C and indomethacin increased the impaired vasodilating response to ACh, whereas the SNP effect was unchanged. In conclusion, in obese subjects, ACh-stimulated vasodilation is blunted, and the increase in FBF is inversely related to BMI, WHR, fasting insulin, and HOMA-IR. The effects of both vitamin C and indomethacin on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction in human obesity.
    Diabetes 01/2001; 50(1):159-65. DOI:10.2337/diabetes.50.1.159 · 8.47 Impact Factor
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    ABSTRACT: We tested the effects of vitamin C and atorvastatin treatment on endothelium-dependent and endothelium-independent vasodilation in 18 hypercholesterolemic patients (ten men and eight women, aged 20-46 years) in comparison with 12 normal volunteers (seven men and five women, aged 20-45 years). The responses of the forearm blood flow (FBF) to acetylcholine (ACh) (7.5, 15 and 30 microg/min), sodium nitroprusside (SNP) (0.8, 1.6, 3.2 microg/min) and L-NMMA (2, 4, 8 micromol/min) were evaluated at baseline and after 1 month of atorvastatin (10 mg/day) treatment. Drugs were infused into the brachial artery and FBF was measured by strain-gauge plethysmography. At baseline, the response to ACh was significantly attenuated in hypercholesterolemics versus controls: at the highest dose (30 microg/min), FBF was 27.0+/-3.4 versus 11.5+/-1.9 ml.100 ml tissue(-1).min(-1) respectively (P<0.0001). No significant differences were found between groups during SNP infusion. The atorvastatin treatment significantly improved ACh-stimulated FBF: at highest dose the FBF increased to 14.9+/-1.5 ml.100 ml tissue(-1). min(-1) (P<0.0001). Similarly, the L-NMMA endothelial effects were significantly enhanced by lipid-lowering treatment, supporting the improvement of basal nitric oxide. Vitamin C increased ACh-vasodilation in the same way before and after atorvastatin treatment. In conclusion, the endothelial dysfunction in hypercholesterolemics is due to an oxidative stress and atorvastatin rapidly improves both basal and stimulated endothelium-dependent vasodilation.
    Atherosclerosis 10/2000; 152(2):511-8. DOI:10.1016/S0021-9150(00)00370-1 · 3.97 Impact Factor
  • F. Perticone · R. Ceravolo · M. Candigliota · A. Mongiardo · G. Cuda
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    ABSTRACT: Cellular stress elicits biochemical responses that either enhance cells survival or lead to cells death or apoptosis. The Ca2+ involvement in apoptosis was demonstrated by several experimental studies using calcium channel blockers (CCBs). Thus, Ca2+ increasing could be an important trigger mechanism for apoptosis. However, the CCBs effects on apoptosis, cells proliferation, cells death induced by oxidative stress remains still unclear. The aim of our study was to assess the effects of amlodipine (AML) (a dydropyridine CCBs) on humbelical vein endothelial cells (HUVEc) stressed with H2O2 (2 mM). We tested the cells death by triphan bleu, and apoptosis by annexin and caspases. The oxidative stress (2 hrs of H2O2 administration) on HUVEc induced a 22% of cells death (Fig. A) and a 20% of apoptosis (Fig. C). On the other hand, AML overnight pretreatment induced a significant reduction of cells death (Fig. B) and apoptosis (Fig. C). The free radical formation (dyclo-roflurescein) in unstressed HUVEc was also significantly reduced by AML treatment (p < 0.0001, by ANOVA). In conclusion, the AML pretreatment reduces cells death and apoptosis, probably, by its antioxidant effects.
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    ABSTRACT: The association between angiotensin-converting enzyme (ACE)-gene polymorphism and insulin resistance (IR) in hypertensives remains controversial. Thus, the aim of present study was to evaluate the possible association between IR and ACE-gene polymorphism and in a group of hypertensive patients in comparison with normotensive control group. We enrolled 200 (114M/86F; age = 45.5 ± 4.7 years) never treated hypertensive patients compared with 96 (54M/42F; age = 44.0 ± 4.7 years) normotensive subjects. Using a double PCR assay identified ACE genotypes. Blood was analyzed for glucose and insulin levels by using the glucose oxidase method and standard radioimmunoassay technique, respectively. IR was estimated by using the homeostasis model assessment (HOMA IR). Both fasting glucose (5.0 ± 0.3 mmol/L vs 4.7 ± 0.3 mmol/L; p < 0.0001) and insulin levels (12.3 ± 4.7 μU/mL vs 4.9 ± 1.5 μU/mL; p < 0.0001) were significantly higher in hypertensive patients than in normotensive control group. HOMA IR was significantly higher (2.7 ± 1.1 vs 1.1 ± 0.3; p < 0.0001) in hypertensives than in normotensives. When we subdivided hypertensive patients according to ACE genotype, we observed: fasting insulin levels and HOMA IR were 16.3 ± 3.3 μU/mL and 3.6 ± 0.8 in DD genotype, 9.4 ± 3.1 μU/mL and 2.1 ± 0.7 in ID, and 8.3 ± 2.8 μU/mL and 1.9 ± 0.7 II group (p < 0.0001, by ANOVA). No significant differences were observed in the normotensive control group. We extended previous data regarding the relationship of hypertension and insulin resistance by demonstrating a dependence of this relationship upon the ACE genotype.
  • American Journal of Hypertension 04/1999; 12(4):71-71. DOI:10.1016/S0895-7061(99)80236-2 · 3.40 Impact Factor
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    ABSTRACT: Am J Hypertens (1999) 12, 195A–195A; doi:10.1016/S0895-7061(99)80705-5 F005: Vitamin C improves acetylcholine-stimulated vasodilation in post-ischemic dilated cardiomyopathy. F. Perticone1, R. Ceravolo1, C. Cosco1, C. Cloro1, S. Iacopino1, M. Candigliota1 and P.L. Mattioli11Dpt of Medicina Sperimentale e Clinica “G Salvatore”, University of Catanzaro, Italy.
    American Journal of Hypertension 03/1999; DOI:10.1016/S0895-7061(99)80705-5 · 3.40 Impact Factor
  • R. Maio · M. Candigliota · F. Perticone · P. L. Mattioli
    Atherosclerosis 12/1997; 135. DOI:10.1016/S0021-9150(97)80003-2 · 3.97 Impact Factor