Vascular Endothelial Dysfunction and Mortality Risk in Patients With Chronic Heart Failure

Katz, Stuart D.; Hryniewicz, Katarzyna; Hriljac, Ingrid; Balidemaj, Kujtim; Dimayuga, Clarito; Hudaihed, Alhakam; Yasskiy, Aleksandr

doi:10.1161/01.cir.0000153349.77489.cf

Cited by 365 publications

(289 citation statements)

References 55 publications

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“…5,[33][34][35] In our present work, of note, despite no significant effect of olmesartan on food intake, olmesartan markedly prevented cardiac inflammation, cardiac interstitial fibrosis, coronary arterial remodeling, and vascular endothelial dysfunction in obese and diabetic mice (Figures 1 and 2). On the other hand, similar blood pressure lowering by hydralazine treatment failed to prevent cardiac remodeling, vascular endothelial dysfunction, and hepatic fibrosis in high-fat diet-fed mice (see Table S1).…”

Section: Discussionsupporting

confidence: 48%

Olmesartan Prevents Cardiovascular Injury and Hepatic Steatosis in Obesity and Diabetes, Accompanied by Apoptosis Signal Regulating Kinase-1 Inhibition

et al. 2008

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Abstract-Dietary obesity is associated with type 2 diabetes and cardiovascular diseases, although the underlying mechanism is unknown. This study was undertaken to elucidate the role of angiotensin II and apoptosis signal regulating kinase-1 (ASK1) in obesity/diabetes-associated cardiovascular complications and hepatic steatosis. Mice fed a high-fat diet were treated with olmesartan, an angiotensin II type 1 receptor blocker, to elucidate the role of angiotensin II in diabetic mice. Treatment of mice fed a high-fat diet with olmesartan markedly suppressed cardiac inflammation and fibrosis, as well as vascular endothelial dysfunction and remodeling, induced by obesity/diabetes. Moreover, olmesartan suppressed the disruption of the vascular endothelial NO synthase dimer in diabetic mice. Olmesartan also significantly prevented hepatic steatosis and fibrosis in diabetic mice. These beneficial effects of olmesartan on diabetic mice were associated with the attenuation of ASK1 activation in these mice. ASK1-deficient mice and wild-type mice were compared, regarding the effects of a high-fat diet. A comparison between ASK1-deficient and wild-type mice showed that ASK1 deficiency attenuated cardiac inflammation and fibrosis, as well as vascular endothelial dysfunction and remodeling induced by obesity/diabetes. The amelioration of vascular endothelial impairment by ASK1 deficiency was attributed to the prevention of endothelial NO synthase dimer disruption. ASK1 deficiency also significantly lessened hepatic steatosis in diabetic mice. In conclusion, our work provided the evidence that ASK1 is significantly activated in diet-induced diabetic mice and contributes to cardiovascular diseases and hepatic steatosis in diabetic mice. Moreover, the beneficial effects of angiotensin II inhibition on dietary diabetic mice seem to be mediated by the inhibition of ASK1 activation. Key Words: diabetes Ⅲ obesity Ⅲ angiotensin Ⅲ ASK1 Ⅲ reactive oxygen species Ⅲ vascular endothelial function Ⅲ cardiac injury O besity, particularly dietary obesity, is associated with type 2 diabetes 1 and an increased risk of cardiovascular diseases. 2-5 However, the underlying mechanism is poorly understood. Accumulating experimental and clinical evidence indicate that the renin-angiotensin system is involved not only in hypertension but also in various cardiovascular diseases. 6 Furthermore, emerging experimental and clinical data support the notion that the renin-angiotensin system participates in the pathophysiology of obesity and type 2 diabetes, 7-13 although the underlying mechanism remains to be elucidated.Reactive oxygen species (ROS) are supposed to be involved in obesity, 14 -17 insulin resistance, diabetes, 1,18 and cardiovascular diseases. 19,20 Apoptosis signal regulating kinase-1 (ASK1), one of the mitogen-activated protein kinase kinase kinases, is markedly activated by ROS and plays a critical role in a variety of cellular responses induced by ROS, including cell apoptosis, growth, differentiation, gene expression, etc. 21-23 Previous...

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Section: Discussionsupporting

confidence: 48%

Olmesartan Prevents Cardiovascular Injury and Hepatic Steatosis in Obesity and Diabetes, Accompanied by Apoptosis Signal Regulating Kinase-1 Inhibition

et al. 2008

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“…Conversely, a few years after the publication by Hare et al, 33 Katz et al showed results similar to ours, where adults with low eNO were more likely to experience the same end point we examined, that of HTx or death 34. Indeed, Hare et al 33 point out, in their discussion, that there are several conflicting studies on eNO and heart failure.…”

Section: Discussionsupporting

confidence: 75%

Low Nasal NO in Congenital Heart Disease With Systemic Right Ventricle and Postcardiac Transplantation

Adams

Zahid

Khalifa

et al. 2017

JAHA

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BackgroundNO bioavailability has not been systematically examined in congenital heart disease (CHD). To assess NO in patients with CHD, we measured nasal NO (nNO) generated by the nasal epithelia, given blood NO is difficult to measure (half‐life, <2 ms). Given NO's role in hemodynamic regulation and the association of NO bioavailability with heart failure risk, we hypothesized NO levels may differ with varying severity of CHD physiologic characteristics.Methods and ResultsSix‐hundred eighteen subjects, 483 with CHD and 135 controls, had nNO measured noninvasively via the nares using American Thoracic Society/European Respiratory Society guidelines. Subjects were dichotomized as having low or normal nNO based on age‐specific cutoff values. Prevalence of low nNO was examined by various CHD physiologic feature types. Low nNO was more prevalent with CHD than controls (odds ratio, 2.28; P=0.001). A logistic regression model showed overall significance (P=0.035) for single ventricle, systemic right ventricle, ventricular dysfunction, oxygen desaturation, and heterotaxy predicting low nNO, with systemic right ventricle independently having twice the odds of low nNO (odds ratio, 2.04; P=0.014). Patients with low nNO had a higher risk of experiencing heart transplant or death (hazard ratio, 2.75; P=0.048), and heart transplant recipients (N=16) exhibited 5 times the odds of low nNO (69% versus 30%; odds ratio, 5.1; P=0.001).ConclusionsPatients with CHD have increased prevalence of low nNO, with highest odds seen with systemic right ventricle and heart transplant. Further studies are needed to investigate heart failure risks in patients with CHD with left versus right systemic ventricle physiologic characteristics and utility of low nNO for predicting heart failure risk.

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“…Vascular endothelial dysfunction is associated with atherosclerosis progression and increased risk of morbidity and mortality in cardiovascular disease populations (22). The increased risk of cardiovascular events in diabetic patients is thought to be partly attributable to vascular endothelial dysfunction caused by altered glucose and insulin metabolism (8,23).…”

Section: Figure 1-flow-mediated Dilation (Fmd In Low-frequency [Low Fmentioning

confidence: 99%

Insulin Sensitivity, Vascular Function, and Iron Stores in Voluntary Blood Donors

et al. 2007

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OBJECTIVE -Reduced iron stores after blood donation are associated with improved vascular function and decreased cardiovascular risk. We sought to determine whether irondependent changes in glucose metabolism may contribute to improved vascular function in blood donors.RESEARCH DESIGN AND METHODS -We conducted a prospective cross-sectional study in 21 high-frequency blood donors (more than eight donations in the last 2 years) and 21 low-frequency blood donors (one to two donations in the last 2 years) aged 50 -75 years. Serum markers of iron stores, whole-body insulin sensitivity index (WBISI) during oral glucose tolerance testing, and flow-mediated dilation in the brachial artery were determined in all subjects.RESULTS -Serum ferritin was decreased (median values 23 vs. 36 ng/ml, P Ͻ 0.05) and flow-mediated dilation in the brachial artery was increased (median values 5.9 vs. 5.3%, P Ͻ 0.05) in high-frequency donors compared with low-frequency donors, respectively, but WBISI (median values 4.8 vs. 4.7) and related measures of glucose tolerance did not differ between groups. Flow-mediated dilation significantly decreased at 1 h after oral glucose loading in both groups, but the decrease in flow-mediated dilation at 1 h did not differ between high-and low-frequency donors.CONCLUSIONS -High-frequency blood donation reduced serum ferritin and increased flow-mediated dilation compared with low-frequency donation but did not improve insulin sensitivity or protect the vascular endothelium from the adverse effects of acute hyperglycemia after oral glucose loading. These findings suggest that the mechanisms linking blood donation to improved vascular function are not likely related to changes in glucose metabolism. Diabetes Care 30:2685-2689, 2007I ron is a prooxidant cofactor that has been proposed to be associated with increased risk of cardiovascular events in humans (1,2). Chronic reduction in iron stores in response to frequent blood donation is associated with improved vascular function in the brachial artery and biochemical evidence of decreased oxidative stress (3). In a randomized trial of patients with peripheral vascular disease, reduction of iron stores with serial phlebotomy decreased mortality compared with conventional therapy in the subjects in the youngest age quartile (aged 43-61 years) (4).A potential mechanistic link between iron stores, vascular function, and cardiovascular risk may be related to irondependent effects on glucose metabolism (5,6). Diabetes is a well-recognized modifiable cardiovascular risk factor associated with increased serum ferritin levels and evidence of vascular endothelial dysfunction (7,8). Iron overload is associated with decreased insulin production, increased insulin resistance, and increased risk of diabetes (5,6). We hypothesized that improved vascular function associated with reduction in iron stores after blood donation might be partly attributable to improved insulin sensitivity. To test this hypothesis, we assessed insulin sensitivity during an oral glucose tolerance...

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Vascular Endothelial Dysfunction and Mortality Risk in Patients With Chronic Heart Failure

Cited by 365 publications

References 55 publications

Olmesartan Prevents Cardiovascular Injury and Hepatic Steatosis in Obesity and Diabetes, Accompanied by Apoptosis Signal Regulating Kinase-1 Inhibition

Olmesartan Prevents Cardiovascular Injury and Hepatic Steatosis in Obesity and Diabetes, Accompanied by Apoptosis Signal Regulating Kinase-1 Inhibition

Low Nasal NO in Congenital Heart Disease With Systemic Right Ventricle and Postcardiac Transplantation

Insulin Sensitivity, Vascular Function, and Iron Stores in Voluntary Blood Donors

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