Adiponectin produced in coronary circulation regulates coronary flow reserve in nondiabetic patients with angiographically normal coronary arteries

Date, Hiroyuki; Imamura, Takuroh; Ideguchi, Takeshi; Kawagoe, Junji; Sumi, Takahiro; Masuyama, Hiroyuki; Onitsuka, Hisamitsu; Ishikawa, Tetsunori; Nagoshi, Toshiro; Eto, Tanenao

doi:10.1002/clc.4960290508

Cited by 25 publications

(23 citation statements)

References 14 publications

(17 reference statements)

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“…A 2008 study demonstrated that local production of adiponectin by microvascular endothelial cells might be involved in the regulation of cardiac function in the diabetic rat heart 56. Similar results were also found in humans; adiponectin levels were found to correlate with microvascular coronary function and coronary blood flow in different regions of the myocardium 57. The possibility exists, therefore, that inflamed microvascular networks are not only directly affected by, but also contribute to, the generalized loss of physiological adiponectin levels in metabolic disease states.…”

Section: Adiponectin and The Microvasculaturementioning

confidence: 77%

Protective vascular and myocardial effects of adiponectin

Goldstein¹,

Scalia²,

L.³

2008

Nat Rev Cardiol

254

200

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SUMMARY Adiponectin is an abundant plasma protein secreted from adipocytes that elicits protective effects in the vasculature and myocardium. In obesity and insulin-resistant states, adiponectin levels are reduced and loss of its protective effects might contribute to the excess cardiovascular risk observed in these conditions. Adiponectin ameliorates the progression of macrovascular disease in rodent models, consistent with its correlation with improved vascular outcomes in epidemiological studies. The mechanisms of adiponectin signaling are multiple and vary among its cellular sites of action. In endothelial cells, adiponectin enhances production of nitric oxide, suppresses production of reactive oxygen species, and protects cells from inflammation that results from exposure to high glucose levels or tumor necrosis factor, through activation of AMP-activated protein kinase and cyclic AMP-dependent protein kinase (also known as protein kinase A) signaling cascades. In the myocardium, adiponectin-mediated protection from ischemia-reperfusion injury is linked to cyclo-oxygenase-2-mediated suppression of tumor necrosis factor signaling, inhibition of apoptosis by AMP-activated protein kinase, and inhibition of excess peroxynitrite-induced oxidative and nitrative stress. In this Review, we provide an update of studies of the signaling effects of adiponectin in endothelial cells and cardiomyocytes.

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Section: Adiponectin and The Microvasculaturementioning

confidence: 77%

Protective vascular and myocardial effects of adiponectin

Goldstein¹,

Scalia²,

L.³

2008

Nat Rev Cardiol

254

200

View full text Add to dashboard Cite

show abstract

“…In obesity, adiponectin levels are decreased (Arita et al 1999), contributing to reduced vascular function (Pilz et al 2005). In the coronary circulation, adiponectin produced by epicardial adipose tissue regulates the cardiac flow reserve (Date et al 2006). …”

Section: Adipokinesmentioning

confidence: 99%

Endothelial dysfunction and diabetes: roles of hyperglycemia, impaired insulin signaling and obesity

et al. 2008

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Endothelial dysfunction comprises a number of functional alterations in the vascular endothelium that are associated with diabetes and cardiovascular disease, including changes in vasoregulation, enhanced generation of reactive oxygen intermediates, inflammatory activation, and altered barrier function. Hyperglycemia is a characteristic feature of type 1 and type 2 diabetes and plays a pivotal role in diabetesassociated microvascular complications. Although hyperglycemia also contributes to the occurrence and progression of macrovascular disease (the major cause of death in type 2 diabetes), other factors such as dyslipidemia, hyperinsulinemia, and adipose-tissue-derived factors play a more dominant role. A mutual interaction between these factors and endothelial dysfunction occurs during the progression of the disease. We pay special attention to the possible involvement of endoplasmic reticulum stress (ER stress) and the role of obesity and adipose-derived adipokines as contributors to endothelial dysfunction in type 2 diabetes. The close interaction of adipocytes of perivascular adipose tissue with arteries and arterioles facilitates the exposure of their endothelial cells to adipokines, particularly if inflammation activates the adipose tissue, and thus affects vasoregulation and capillary recruitment in skeletal muscle. Hence, an initial dysfunction of endothelial cells underlies metabolic and vascular alterations that contribute to the development of type 2 diabetes.

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“…19) We previously reported that adiponectin is locally produced in the coronary circulation and might participate in modulating the coronary circulation in individuals with normal coronary arteries. 13) We speculate that adiponectin secreted from epicardial fat directly affects the coronary artery in a vasocrine or paracrine manner. 20) We also reported that patients with CAD had lower adiponectin production in the coronary circulation than non-CAD patients; 14) however, in some patients with CAD, adiponectin in GCV was lower than in LCA, namely the adiponectin-negative production group in the present study.…”

Section: Discussionmentioning

confidence: 89%

“…13) We also reported that signifi cantly less adiponectin was produced locally in the coronary circulation of patients with than without CAD. 14) These fi ndings suggested that lower adiponectin production in the coronary circulation is related to the progression of coronary atherosclerosis; however, there is uncertainty about the association of adiponectin production levels in the coronary circulation with CAD and MACE.…”

mentioning

confidence: 84%

Association Between Adiponectin Production in Coronary Circulation and Future Cardiovascular Events in Patients With Coronary Artery Disease

Kawagoe

Ishikawa

Iwakiri³

et al. 2014

Int. Heart J.

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SummaryAdiponectin has antiatherosclerotic properties and is also produced in the local coronary circulation. We previously reported that signifi cantly less adiponectin was produced in the coronary circulation of patients with than without coronary artery disease (CAD). The goal of this study was to determine whether adiponectin production in the coronary circulation could predict future cardiovascular events in patients with CAD.Forty-eight CAD patients whose left anterior descending coronary arteries required percutaneous coronary intervention (PCI) were enrolled. The amount of adiponectin production in the coronary circulation was defi ned as the plasma adiponectin level at the great cardiac vein minus that at the orifi ce of the left coronary artery. All patients were divided by adiponectin production level in the coronary circulation into the adiponectin-positive production group (> 0 µg/ mL) and adiponectin-negative production group (≤ 0 µg/mL). Median follow-up period was 66 months (maximum, 108 months). The primary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization due to unstable angina, heart failure, nonfatal myocardial infarction, revascularization with PCI or coronary artery bypass grafting, ischemic stroke, and cardiovascular death.Sixteen MACE occurred. The incidence of MACE was signifi cantly higher in the adiponectin-negative production group than in the adiponectin-positive production group (P = 0.02). In multivariate analysis, adiponectin-negative production was a predictor of MACE (P = 0.03). Kaplan-Meier analysis revealed that the MACE-free rate was signifi cantly lower in the adiponectin-negative production group than in the adiponectin-positive production group.Adiponectin production in the coronary circulation with CAD may be associated with MACE. (Int Heart J 2014; 55: 239-243)

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Adiponectin produced in coronary circulation regulates coronary flow reserve in nondiabetic patients with angiographically normal coronary arteries

Cited by 25 publications

References 14 publications

Protective vascular and myocardial effects of adiponectin

Protective vascular and myocardial effects of adiponectin

Endothelial dysfunction and diabetes: roles of hyperglycemia, impaired insulin signaling and obesity

Association Between Adiponectin Production in Coronary Circulation and Future Cardiovascular Events in Patients With Coronary Artery Disease

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