Serum Resistin is Associated With High Risk in Patients With Congestive Heart Failure A Novel Link Between Metabolic Signals and Heart Failure

Takeishi, Yasuchika; Niizeki, Takeshi; Arimoto, Takanori; Nakatani, Naoki; Hirono, Osamu; Nitobe, Joji; Watanabe, Tetsu; Takabatake, Noriaki; Kubota, Isao

doi:10.1253/circj.71.460

Cited by 92 publications

(82 citation statements)

References 21 publications

(36 reference statements)

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“…Resistin has been reported to contribute to the worsening of ischemia/reperfusion injury in isolated rat heart preparations [39] and to be associated with high risk in patients with congestive heart failure [40]. In addition, elevated resistin levels correlated with endothelial dysfunction [41] and with the development of atherosclerosis in mice and in patients with premature coronary artery disease [42].…”

Section: Discussionmentioning

confidence: 99%

Role of resistin in cardiac contractility and hypertrophy

Kim

Satoh

et al. 2008

Journal of Molecular and Cellular Cardiology

141

120

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Cardiovascular sequelae including diabetic cardiomyopathy constitute the major cause of death in diabetic patients. Although several factors may contribute to the development of this cardiomyopathy, the underlying molecular/cellular mechanisms leading to cardiac dysfunction are still partially understood. Recently, a novel paradigm for the role of the adipocytokine resistin in diabetes has emerged. Resistin has been proposed to be a link between obesity, insulin resistance and diabetes. Using microarray analysis, we have recently found that cardiomyocytes isolated from type 2 diabetic hearts express high levels of resistin. However, the function of resistin with respect to cardiac function is unknown. In this study we show that resistin is not only expressed in the heart, but also promotes cardiac hypertrophy. Adenovirus-mediated overexpression of resistin in cultured neonatal rat ventricular myocytes (NRVM) significantly increased sarcomere organization and cell size, increased protein synthesis and increased the expression of atrial natriuretic factor and β-myosin heavy chain. Overexpression of resistin in NRVM was also associated with activation of the mitogenactivated protein (MAP) kinases, ERK1/2 and p38, as well as increased Ser-636 phosphorylation of insulin receptor substrate-1 (IRS-1), indicating that IRS-1/MAPK pathway may be involved in the observed hypertrophic response. Overexpression of resistin in adult cultured cardiomyocytes significantly altered myocyte mechanics by depressing cell contractility as well as contraction and relaxation velocities. Intracellular Ca 2+ measurements showed slower Ca 2+ transients decay in resistin-transduced myocytes compared to controls, suggesting impaired cytoplasmic Ca 2+ clearing or alterations in myofilament activation. We conclude that resistin overexpression alters cardiac contractility, confers to primary cardiomyocytes all the features of the hypertrophic phenotype and promotes cardiac hypertrophy possibly via the IRS-1/MAPK pathway.

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Section: Discussionmentioning

confidence: 99%

Role of resistin in cardiac contractility and hypertrophy

Kim

Satoh

et al. 2008

Journal of Molecular and Cellular Cardiology

141

120

View full text Add to dashboard Cite

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“…Indeed, in a study of patients hospitalized for heart failure, in which 27% patients were ischemic cardiomyopathy, serum resistin was related to the severity of heart failure and a high risk for adverse cardiac events. 24 Recently revascularization by PCI or thrombolysis have become the main therapy in ACS. However, ischemia reperfusion injury is an emerging problem that impairs myocardium and cardiac function.…”

Section: Discussionmentioning

confidence: 99%

Plasma Resistin Associated With Myocardium Injury in Patients With Acute Coronary Syndrome

Chu

Ding

et al. 2008

Circ J

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esistin was first found in 2001 by Steppan and coworkers as a novel peptide synthesized and secreted from murine adipocytes. 1 Circulating resistin level was increased in diet-induced and genetic forms of obesity but could be decreased using rosiglitazone therapy. Administration of anti-resistin antibodies improved blood glucose control and insulin action in mice with dietinduced obesity. 1 Resistin is thought to be an adipokine associated with insulin resistance.Subsequent studies of its role in human obesity and insulin resistance, however, showed conflicting results. 2 Contrary to the distribution in rodents, in humans, the main sources of resistin seem to be monocytes and macrophages. 3 Resistin level was positively associated with levels of inflammatory markers, including soluble tumor necrosis factor-receptor-2, interleukin-6 and lipoprotein-associated phospholipase A2. 4 Moreover, resistin up-regulates the expression of adhesion molecules in cultured endothelial cells and promotes the proliferation of smooth muscle cells, which suggests that it may be an inflammatory marker. 4 inflammation and atherosclerosis. 7,8 Indeed, resistin levels were also correlated with high-sensitivity C-reactive protein (hs-CRP) level, insulin level and homeostasis model assessment of insulin resistance. In a study adjusting for age, sex and established risk factors, the concentration of resistin was also associated with increasing coronary artery calcification (CAC); resistin levels further predicted CAC in subjects with metabolic syndrome. 4 Also, Ohmori reported resistin levels increased in 157 patients with coronary artery disease, even after adjusting for age and gender. Resistin levels were found to increase stepwise, depending on number of stenotic vessels and/or segments. 7 Acute coronary syndrome (ACS) is an acute cardiac event resulting from rupture of vulnerable atherosclerotic plaque in the coronary artery. In ACS, a large amount of inflammatory cells and cytokines are released to the circulation and accelerate the development of atherosclerosis, which results from chronic metabolic abnormality. In the present study, we observed plasma resistin level in patients with ACS during the first week after symptom onset, analyzed the relation of plasma resistin level and clinical index, and investigated the potential significance of resistin in ACS pathogenesis. Method SubjectsThe study was reviewed and approved by the Ethics Committee of Peking University First Hospital, and informed consent was obtained from each subject before the study began. The aim of the present study was to investigate the alteration in level of plasma resistin in patients with acute coronary syndrome (ACS) to uncover the role of resistin. Methods and ResultsThe 39 patients with ACS and 26 age-matched healthy subjects in this cross-sectional study were investigated. Plasma resistin levels were measured using radioimmunoassay. Plasma resistin levels were significantly increased in patients with ACS at 24 h after symptoms onset and remained at a high...

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“…45 ), whose inhibition results in a significant decrease in LDL cholesterol. Serum resistin levels are elevated in people with heart failure and levels positively correlate with severity of heart failure according to the NYHA classification 46 . Interestingly, the opposite results were obtained in the case omentin (see below).…”

Section: Resistinmentioning

confidence: 99%