Adipose Tissue Inflammation and Adiponectin Resistance in Patients With Advanced Heart Failure

Khan, Raffay; Kato, Tomoko S.; Chokshi, Aalap; Chew, Michael; Yu, Shan; Wu, Christina; Singh, Parvati; Cheema, Faisal H.; Takayama, Hiroo; Harris, Collette; Reyes‐Soffer, Gissette; Knöll, Ralph; Milting, Hendrik; Naka, Yoshifumi; Mancini, Donna; Schulze, P. Christian

doi:10.1161/circheartfailure.111.964031

Cited by 87 publications

(45 citation statements)

References 32 publications

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“…In support of our findings, Bobbert and colleagues have reported the increase of adverse clinical events for patients with cardiomyopathy, which is associated with higher levels of circulating resistin levels 31 . On this same spectrum, heart failure patients destined for left ventricular assist device (LVAD) therapy show elevated resistin levels compared to the control groups until LVAD implantation, after which implantation resulted in a downward trend in plasma resistin 32 .…”

Section: Discussionmentioning

confidence: 99%

The association of resistin with cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

Muse¹,

Feldman²,

Blaha³

et al. 2015

Atherosclerosis

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Objective To describe the relationship between circulating resistin levels and cardiovascular diseases (CVD) and all-cause death in a multi-ethnic cohort. Methods and Results We studied 1,913 participants from the Multi-Ethnic Study of Atherosclerosis with measurements of plasma resistin levels. Absolute proportions experiencing new-onset atrial fibrillation (AF), atherosclerotic CVD (myocardial infarction, angina, resuscitated cardiac arrest, stroke), heart failure (HF), and all-cause death were calculated for each quartile of resistin. We used adjusted Cox proportional regression modeling resistin as a continuous variable per standard deviation of log-transformed resistin and secondarily as a categorical variable using resistin quartiles. Results were stratified by sex and race/ethnicity. The mean age of the population was 64.5 ± 10 years with half being female and a median resistin concentration of 15.1 ng/mL (11.9–19.1). Mean follow-up time was 7.2 ± 1.8 years. There was a graded increase in the occurrence of all outcomes across increasing quartiles of resistin. Modeled as a continuous variable, after adjustment for anthropomorphic measures, traditional risk factors, markers of inflammation, and other adipokines, significant associations were noted for HF (HR 1.4, CI 1.0–2.0), hard and all CVD (HR 1.3, 1.1–1.7 and 1.3, 1.1–1.6, respectively), and CHD (HR 1.31, 1.0–1.6), but not for AF or death. Significant interaction terms were noted between resistin and race, with Hispanic race/ethnicity showing the strongest relationship between resistin and outcomes. Conclusions In an ethnically diverse population without known CVD at baseline, there was a strong, independent association between higher resistin levels and incident CVD, CHD and HF.

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Section: Discussionmentioning

confidence: 99%

The association of resistin with cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

Muse¹,

Feldman²,

Blaha³

et al. 2015

Atherosclerosis

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“…Another possible explanation for the conflicting results is that elevated levels of adiponectin might mirror an impaired adiponectin signalling in patients with cardiovascular disease. Khan et al 18 found that, in patients with advanced heart failure, increased levels of adiponectin were accompanied by downregulation of adiponectin receptors in the myocardium. Adiponectin resistance might therefore also explain the direct association between adiponectin and PWV in patients after STEMI.…”

Section: Discussionmentioning

confidence: 99%

“…ultrasound techniques), PC-CMR is not affected by geometrical assumptions on the course and length of the aorta and the need for an accurate acoustic window. 8,17 Because of the inverse correlation of adiponection with aortic stiffness in recent cohort studies 5,18 and the conflicting results in patients with established CAD, 13 we sought to investigate the relationship between plasma levels of adiponectin and PWV after STEMI for the first time.…”

Section: Introductionmentioning

confidence: 99%

Relation of plasma adiponectin levels and aortic stiffness after acute ST-segment elevation myocardial infarction

Reinstadler

Klug

Feistritzer

et al. 2013

European Heart Journal: Acute Cardiovascular Care

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Background: Pulse wave velocity is a measure of aortic stiffness and an independent predictor of cardiovascular morbidity and mortality. Adiponectin is involved in atherosclerosis and inflammation. In the present study we aimed to explore the association between plasma adiponectin concentrations and pulse wave velocity in the acute phase after STsegment elevation myocardial infarction (STEMI). Methods: Forty-six consecutive STEMI patients (mean age 57±11 years) treated with primary percutaneous coronary intervention (PCI) were enrolled in this cross-sectional study. Plasma adiponectin was measured 2 days after index event by enzyme-linked immunosorbent assay. Aortic pulse wave velocity (PWV) was calculated by the transit-time method with the use of a velocity-encoded, phase-contrast cardiac magnetic resonance protocol. Results: Median plasma adiponectin concentration was 2385 ng/ml (interquartile range 1735-5403). Males had lower plasma adiponectin values than females and current smokers had lower values than non-smokers (all p<0.02). Adiponectin was significantly associated with PWV (r=0.505, p<0.001), age (r=0.437, p=0.002), and total cholesterol (r=0.468, p=0.001). Multiple linear regression analysis revealed adiponectin as a predictor of PWV independently of age, sex, smoking status, total cholesterol, and N-terminal pro-B-type natriuretic peptide (p=0.027). Conclusions: Plasma adiponectin concentrations are strongly associated with aortic stiffness in patients after acute STEMI treated with primary PCI. Our data support a possible role for adiponectin as an independent risk marker for increased aortic stiffness in STEMI patients.

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“…However, higher adiponectin serum levels are reported to correlate with increased mortality in patients with chronic heart failure (Beatty et al, 2012), thus raising questions about the beneficial role of adiponectin. It is likely that functional adiponectin resistance develops in patients with advanced heart failure with down regulation of adiponectin receptors (Springer et al, 2010;Khan et al, 2012). These findings indicate the importance to clearly delineating the downstream signaling and cross-talk of adiponectin regulation before we can use adiponectin as a future therapeutic regimen for cardiovascular disease.…”

Section: Adiponectin Attenuates Iron-overload Cardiomyopathymentioning

confidence: 99%

Adiponectin Ameliorates Iron-Overload Cardiomyopathy through the PPARα–PGC-1–Dependent Signaling Pathway

et al. 2013

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Adiponectin is a circulating adipose-derived cytokine that may act as an antioxidative and anti-inflammatory protein. Although adiponectin has been reported to exert cytoprotective effects in acute cardiac diseases, its effects on chronic heart failure are less clear. Therefore, we aimed to investigate whether adiponectin would have a beneficial effect in iron-induced chronic heart failure and to elucidate its regulation in cardiomyocytes. Mice were first treated with iron dextran for 4 weeks to induce iron-overload cardiomyopathy. They exhibited decreased survival with impaired left ventricle contractility and decreased serum adiponectin levels. In vivo cardiac adiponectin gene (ADIPOQ) overexpression with adenoassociated virus (AAV)-ADIPOQ ameliorated cardiac iron deposition and restored cardiac function in iron-overloaded mice. In addition, AAV-ADIPOQ-treated iron-overload mice had lower expression of inflammatory markers, including myeloperoxidase activity, monocyte chemotactic protein-1, tumor necrosis factor-a, interleukin-6, and intercellular adhesion molecule-1, than iron-overloaded mice not treated with AAV-ADIPOQ. Our in vitro study showed that adiponectin induced heme oxygenase-1 (HO-1) expression through the peroxisome proliferator-activated receptor (PPAR)a-HO-1 signaling pathway. Furthermore, the adiponectin-mediated beneficial effects were PPARa-dependent as the adiponectinmediated attenuation of iron deposition was abolished in PPARa-knockout mice. Finally, PPARa-HO-1 signaling involved PPARa and peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) binding and nuclear translocation, and their levels were increased by adiponectin therapy. Together, these findings suggest that adiponectin acts as an antiinflammatory signaling molecule and induces the expression of HO-1 through the PPARa-PGC-1 complex-dependent pathway in cardiomyocytes, resulting in the attenuation of iron-induced cardiomyopathy. Using adiponectin for adjuvant therapies in iron-overload cardiac dysfunction may be an option in the future.

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Adipose Tissue Inflammation and Adiponectin Resistance in Patients With Advanced Heart Failure

Cited by 87 publications

References 32 publications

The association of resistin with cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

The association of resistin with cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

Relation of plasma adiponectin levels and aortic stiffness after acute ST-segment elevation myocardial infarction

Adiponectin Ameliorates Iron-Overload Cardiomyopathy through the PPARα–PGC-1–Dependent Signaling Pathway

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