Role of endothelial dysfunction in heart failure

Zuchi, Cinzia; Tritto, Isabella; Carluccio, Erberto; Mattei, Cristian; Cattadori, Gaia; Ambrosio, Giuseppe

doi:10.1007/s10741-019-09881-3

Cited by 117 publications

(109 citation statements)

References 105 publications

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“…Another factor that may lead to diminished functional capacity and reduced LBM is endothelial dysfunction, 29 which was shown to be present in Chagas disease patients without HF 30 and also in patients with HF regardless of aetiology 31 . In our study, patients with Chagas disease and HF showed a reduction in FBF compared with the other two aetiologies ( Figure ), and this decrease in peripheral blood flow was positively correlated with muscle strength, LBM, and ALM ( Figure ).…”

Section: Discussionsupporting

confidence: 56%

Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies

et al. 2020

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Aims Patients with Chagas disease and heart failure (HF) have a poor prognosis similar to that of patients with ischaemic or dilated cardiomyopathy. However, the impact of body composition and muscle strength changes in these aetiologies is still unknown. We aimed to evaluate these parameters across aetiologies in two distinct cohort studies [TESTOsterone-Heart Failure trial (TESTO-HF; Brazil) and Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF; Germany)]. Methods and results A total of 64 male patients with left ventricular ejection fraction ≤40% were matched for body mass index and New York Heart Association class, including 22 patients with Chagas disease (TESTO-HF; Brazil), and 20 patients with dilated cardiomyopathy and 22 patients with ischaemic heart disease (SICA-HF; Germany). Lean body mass (LBM), appendicular lean mass (ALM), and fat mass were assessed by dual energy X-ray absorptiometry. Sarcopenia was defined as ALM divided by height in metres squared <7.0 kg/m 2 (ALM/height 2) and handgrip strength cutoff for men according to the European Working Group on Sarcopenia in Older People. All patients performed maximal cardiopulmonary exercise testing. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Chagasic and ischaemic patients had lower total fat mass (16.3 ± 8.1 vs. 19.3 ± 8.0 vs. 27.6 ± 9.4 kg; P < 0.05) and reduced peak oxygen consumption (VO 2) (1.17 ± 0.36 vs. 1.15 ± 0.36 vs. 1.50 ± 0.45 L/min; P < 0.05) than patients with dilated cardiomyopathy, respectively. Chagasic patients showed a trend towards decreased LBM when compared with ischaemic patients (48.3 ± 7.6 vs. 54.2 ± 6.3 kg; P = 0.09). Chagasic patients showed lower handgrip strength (27 ± 8 vs. 37 ± 11 vs. 36 ± 14 kg; P < 0.05) and FBF (1.84 ± 0.54 vs. 2.75 ± 0.76 vs. 3.42 ± 1.21 mL/min/100 mL; P < 0.01) than ischaemic and dilated cardiomyopathy patients, respectively. There was no statistical difference in the distribution of sarcopenia between groups (P = 0.87). In addition, FBF correlated positively with LBM (r = 0.31; P = 0.012), ALM (r = 0.25; P = 0.046), and handgrip strength (r = 0.36; P = 0.004). In a logistic regression model using peak VO 2 as the dependent variable, haemoglobin (odds ratio, 1.506; 95% confidence interval, 1.043-2.177; P = 0.029) and ALM (odds ratio, 1.179; 95% confidence interval, 1.011-1.374; P = 0.035) were independent predictors for peak VO 2 adjusted by age, left ventricular ejection fraction, New York Heart Association, creatinine, and FBF. Conclusions Patients with Chagas disease and HF have decreased fat mass and exhibit reduced peripheral blood flow and impaired muscle strength compared with ischaemic HF patients. In addition, patients with Chagas disease and HF show a tendency to have greater reduction in total LBM, with ALM remaining an independent predictor of reduced functional capacity in these patients. The percentage of patients affected by sarcopenia was equal between groups.

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Section: Discussionsupporting

confidence: 56%

Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies

et al. 2020

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“…In fact, in contrast to our results, previous literature data have merely shown that endothelium-dependent vasodilation is blunted in patients with HF, which, in turn, contributes to the worsening of its progression. [14][15][16][17][18] The underlying pathogenetic mechanisms involved in this association may be recognized in an excess of oxidative stress that reduces the bioavailability of NO, induces a neurohormonal activation with associated release of inflammatory mediators, and produces alterations of local shear stress due to low cardiac output. 14 In addition, pre-existing traditional cardiovascular risk factors also contribute, through the increase in oxidative stress again, to the vascular motricity impairment, whose association with endothelial dysfunction has well established from long time.…”

Section: Discussionmentioning

confidence: 99%

“…As a consequence of the worldwide increase of cardiovascular risk factors, both coronary artery disease and diabetes represent the major underlying pathogenetic mechanisms involved in the appearance and progression of HF. It is likely that endothelial dysfunction contributes to HF appearance with different mechanisms, such as the reduction of vasoreactivity of epicardial and small coronary vessels, the after‐load increase, myocardial oxidative stress, and fibrotic process 14,15 . Conversely, several findings demonstrated that peripheral endothelial dysfunction is present in patients with chronic HF, in those with both reduced and preserved ejection fraction 15–18 .…”

Section: Introductionmentioning

confidence: 99%

Endothelial dysfunction and C‐reactive protein predict the incidence of heart failure in hypertensive patients

et al. 2020

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Aims Endothelial dysfunction and heart failure are associated, but no prospective studies demonstrated that impaired endothelium‐dependent vasodilation predicts incident heart failure. We designed this study to test whether endothelial dysfunction is associated with incident heart failure in a group of hypertensives. Methods and results We enrolled 735 White never‐treated hypertensive outpatients free from heart failure, diabetes, chronic kidney disease, and previous cardiovascular events. Endothelium‐dependent vasodilation was investigated by intra‐arterial infusion of acetylcholine, and laboratory determinations were obtained by standard procedures. During the follow‐up [median 114 months (range 26–206)], there were 208 new cases of heart failure (3.1 events/100 patient‐years). Dividing the study population in progressors and non‐progressors, we observed that progressors were older, showed a higher prevalence of being female, and had a higher baseline heart rate, glucose, insulin, Homeostatic Model Assessment (HOMA), creatinine, and high‐sensitivity C‐reactive protein (hs‐CRP) mean values, while estimated glomerular filtration rate and maximal acetylcholine‐stimulated forearm blood flow were lower. In the multiple Cox regression analysis, female gender [hazard ratio (HR) = 1.454, 95% CI = 1.067–1.981], fasting glucose (HR = 1.186, 95% CI = 1.038–1.357), hs‐CRP (HR = 1.162, 95% CI = 1.072–1.259), HOMA (HR = 1.124, 95% CI = 1.037–1.219), acetylcholine‐stimulated forearm blood flow (HR = 0.779, 95% CI = 0.695–0.874), and estimated glomerular filtration rate (HR = 0.767, 95% CI = 0.693–0.849) maintained an independent association with the outcome. Successively, testing the interaction between forearm blood flow and hs‐CRP, we observed that patients who have hs‐CRP values above the median and forearm blood flow under the median show a higher risk of developing heart failure (HR = 7.699, 95% CI = 4.407–13.451). Conclusions The present data demonstrate that an impaired endothelium‐dependent vasodilation and hs‐CRP predict development of incident heart failure in hypertensives.

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“…Endothelial cells that line the interior surface of blood vessels are particularly susceptible to OS, mainly resulting from ROS production by neutrophils and other PMNs as well as by endothelial cells themselves [ 172 ]. It is well known that OS-induced vascular endothelial dysfunction plays a significant role in the pathophysiology of multiple cardiovascular diseases, including I/R injury, hypertension, heart failure, diabetes, pulmonary inflammation and atherosclerosis [ 23 , 24 , 28 , [173] , [174] , [175] , [176] , [177] , [178] , [179] ]. Hecquet et al were the first to examine endothelial expression of the TRPM2 channel using human pulmonary artery endothelial cells [ 74 ].…”

Section: Trpm2 In Endothelial Cell Death Associated With Vascular Dysmentioning

confidence: 99%

“…Such an imbalance can lead to the accumulation of ROS at high levels that induces a noxious condition termed oxidative stress (OS) [ 4 ]. A wealth of evidence exists to indicate that OS is an important pathological factor for, as well as a salient feature of, various diseases and conditions, including ischemia/reperfusion (I/R) damage, Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, neurovascular dysfunction, cardiovascular disorders, diabetes, pancreatitis, chronic kidney disease, liver injury, hearing loss, inflammatory diseases, and cancers [ 3 , 6 , 7 , 10 , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] ].…”

Section: Introductionmentioning

confidence: 99%

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

Malko

Jiang

2020

Redox Biology

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Oxidative stress resulting from the accumulation of high levels of reactive oxygen species is a salient feature of, and a well-recognised pathological factor for, diverse pathologies. One common mechanism for oxidative stress damage is via the disruption of intracellular ion homeostasis to induce cell death. TRPM2 is a non-selective Ca 2+ -permeable cation channel with a wide distribution throughout the body and is highly sensitive to activation by oxidative stress. Recent studies have collected abundant evidence to show its important role in mediating cell death induced by miscellaneous oxidative stress-inducing pathological factors, both endogenous and exogenous, including ischemia/reperfusion and the neurotoxicants amyloid-β peptides and MPTP/MPP + that cause neuronal demise in the brain, myocardial ischemia/reperfusion, proinflammatory mediators that disrupt endothelial function, diabetogenic agent streptozotocin and diabetes risk factor free fatty acids that induce loss of pancreatic β-cells, bile acids that damage pancreatic acinar cells, renal ischemia/reperfusion and albuminuria that are detrimental to kidney cells, acetaminophen that triggers hepatocyte death, and nanoparticles that injure pericytes. Studies have also shed light on the signalling mechanisms by which these pathological factors activate the TRPM2 channel to alter intracellular ion homeostasis leading to aberrant initiation of various cell death pathways. TRPM2-mediated cell death thus emerges as an important mechanism in the pathogenesis of conditions including ischemic stroke, neurodegenerative diseases, cardiovascular diseases, diabetes, pancreatitis, chronic kidney disease, liver damage and neurovascular injury. These findings raise the exciting perspective of targeting the TRPM2 channel as a novel therapeutic strategy to treat such oxidative stress-associated diseases.

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Role of endothelial dysfunction in heart failure

Cited by 117 publications

References 105 publications

Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies

Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies

Endothelial dysfunction and C‐reactive protein predict the incidence of heart failure in hypertensive patients

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

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