Valsartan improves resting skin blood flow in type 2 diabetic patients and reduces poly(adenosine diphosphate-ribose) polymerase activation

Shrikhande, Gautam; Khaodhiar, Lalita; Scali, Salvatore T.; Lima, Christina; Hubbard, Matthew; Dudley, Katherine A.; Ganda, Om P; Ferran, Christiane; Veves, Aristidis

doi:10.1016/j.jvs.2005.12.059

Cited by 20 publications

(15 citation statements)

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“…A recent study that included diabetic patients without hypertension or heart disease who were treated for 6 months with candesartan, another ARB, showed an improvement in diastolic dysfunction and attenuation of myocardial fibrosis, suggesting that ARBs may regulate collagen turnover by facilitating collagen degradation [20]. Previous studies in our unit have shown that valsartan treatment for 3 months, at the same dose as in the present study, results in considerable improvement of blood flow in the skin microcirculation of diabetic patients but had no effect in the skin microcirculation of healthy control subjects [21]. Furthermore, the same studies indicated that valsartan exerts its beneficial effects by reducing the activity of poly (adenosine diphosphate-ribose) polymerase, which is increased in diabetes and is associated with endothelial dysfunction [22,23].…”

Section: Discussionsupporting

confidence: 59%

Effect of valsartan on left ventricular anatomy and systolic function and aortic elasticity

et al. 2009

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Section: Discussionsupporting

confidence: 59%

Effect of valsartan on left ventricular anatomy and systolic function and aortic elasticity

et al. 2009

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“…All techniques were performed according to published guidelines (8). The skin blood flow was evaluated by employing a LASER Doppler Perfusion Imager (LDPI Lisca 2.0, Lisca Development AB, Linkoping, Sweden), as previously described (9). The above methods, including information regarding their coefficient of variation, have been previously described (7,8,9).…”

Section: Methods and Proceduresmentioning

confidence: 99%

“…The skin blood flow was evaluated by employing a LASER Doppler Perfusion Imager (LDPI Lisca 2.0, Lisca Development AB, Linkoping, Sweden), as previously described (9). The above methods, including information regarding their coefficient of variation, have been previously described (7,8,9). Vascular reactivity was measured in 165 subjects (22 healthy nonobese nondiabetic control subjects, 40 nonobese diabetic patients, 31 obese nondiabetic, control subjects, and 72 obese diabetic patients).…”

Section: Methods and Proceduresmentioning

confidence: 99%

Effects of Diabetes and Obesity on Vascular Reactivity, Inflammatory Cytokines, and Growth Factors

Doupis

Rahangdale

Gnardellis

et al. 2011

Obesity

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We examined the influences of obesity and diabetes on endothelium-dependent and -independent vasodilation, inflammatory cytokines, and growth factors. We included 258 subjects, age 21–80 years in four groups matched for age and gender: 40 healthy nonobese (BMI <30 kg·m−2) nondiabetic subjects, 76 nonobese diabetic patients, 37 obese (BMI >30) nondiabetic subjects, and 105 obese (BMI >30) diabetic patients. The flow-mediated dilation (FMD, endothelium-dependent) and nitroglycerin-induced dilation (NID, endothelium-independent) in the brachial artery, the vascular reactivity at the forearm skin and serum growth factors and inflammatory cytokines were measured. FMD was reduced in the nonobese diabetic patients, obese nondiabetic controls, and obese diabetic patients (P < 0.0001). NID was different among all four groups, being highest in the obese nondiabetic subjects and lowest in the obese diabetic patients (P < 0.0001). The resting skin forearm blood flow was reduced in the obese nondiabetic subjects (P < 0.01). Vascular endothelial growth factor (VEGF) was higher in the obese nondiabetic subjects (P < 0.05), tumor necrosis factor–α was higher in the obese diabetic patients (P < 0.0001) and C-reactive protein was higher in both the obese nondiabetic and diabetic subjects (P < 0.0001). Soluble intercellular adhesion molecule-1 was elevated in the two diabetic groups and the obese nondiabetic subjects (P < 0.05). We conclude that diabetes and obesity affect equally the endothelial cell function but the smooth muscle cell function is affected only by diabetes. In addition, the above findings may be related to differences that were observed in the growth factors and inflammatory cytokines.

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“…DM2 is a common co-morbidity encountered with peripheral arterial disease (PAD), and together account for the majority of non-traumatic amputations among the diabetic population. Studies have demonstrated that in human diabetic tissues there is an increase in oxidative, nitrosative stresses and genomic instability, leading to an up-regulation in poly ADP-Ribose polymerase activity (PARP) 3–6 . PARP is a nuclear and mitochondrial enzyme involved in numerous cellular activities, including DNA repair, maintenance of genomic integrity, modulation of various proteins at the transcriptional and post-transcriptional levels, regulation of cell death, cellular replication and differentiation 7, 8 .…”

Section: Introductionmentioning

confidence: 99%

“…Under pathologic conditions however, extensive PARP activation in response to stress can lead to NAD+ depletion, which compromises glycolysis and ATP generation 5, 9 . Increased PARP activity is believed to play a critical role in the etiology of vascular injury and complications seen in DM2 patients by decreasing vasomotor reactivity in skin and systemic arteries 6, 10, 11 .…”

Section: Introductionmentioning

confidence: 99%

Poly-ADP-Ribose-Polymerase Inhibition Ameliorates Hind Limb Ischemia Reperfusion Injury in a Murine Model of Type 2 Diabetes

et al. 2013

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Introduction Diabetes is known to increase poly-ADP-ribose-polymerase (PARP) activity and posttranslational poly-ADP-ribosylation of several regulatory proteins involved in inflammation and energy metabolism. These experiments test the hypothesis that PARP inhibition will modulate hind limb ischemia reperfusion (IR) in a mouse model of type-II diabetes; ameliorate the ribosylation and the activity/transnuclear localization of the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Methods db/db mice underwent 1.5hrs of hind limb ischemia followed by 1, 7, or 24hrs reperfusion. The treatment group received the PARP inhibitor PJ34 (PJ34) over a 24hrs period; the untreated group received Lactated ringer’s (LR) at the same time points. IR muscles were analyzed for indices of PARP activity, fiber injury, metabolic activity, inflammation, GAPDH activity /intracellular localization and poly-ADP-ribosylation of GAPDH. Results PARP activity was significantly lower in the PJ34 treated groups compared to the LR group at 7 and 24 hours reperfusion. There was significantly less muscle fiber injury in the PJ34 treated group compared to LR treated mice at 24 hrs reperfusion. PJ34 lowered levels of select proinflammatory molecules at 7hrs and 24hrs IR. There were significant increases in metabolic activity only at 24 hours IR in the PJ34 group, which temporally correlated with increase in GAPDH activity, decreased GAPDH poly ADP-ribosylation and nuclear translocation of GAPDH. Conclusions PJ34 reduced PARP activity, GAPDH ribosylation, GAPDH translocation, ameliorated muscle fiber injury, and increased metabolic activity following hind limb IR injury in a murine model of type-II diabetes. PARP inhibition might be a therapeutic strategy following IR in diabetic humans.

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Valsartan improves resting skin blood flow in type 2 diabetic patients and reduces poly(adenosine diphosphate-ribose) polymerase activation

Abstract: Valsartan increases the resting skin blood flow in T2DM, likely through reduction of PARP activity.

Cited by 20 publications

References 35 publications

Effect of valsartan on left ventricular anatomy and systolic function and aortic elasticity

Effect of valsartan on left ventricular anatomy and systolic function and aortic elasticity

Effects of Diabetes and Obesity on Vascular Reactivity, Inflammatory Cytokines, and Growth Factors

Poly-ADP-Ribose-Polymerase Inhibition Ameliorates Hind Limb Ischemia Reperfusion Injury in a Murine Model of Type 2 Diabetes

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