Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a risk factor for the development of cardiovascular diseases that are associated with impaired angiogenesis. Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties, and its plasma levels are reduced in association with obesity-linked diseases. Here, we investigated whether adiponectin regulates angiogenesis in response to tissue ischemia using adiponectin knock-out (KO) mice. Angiogenic repair of ischemic hind limbs was impaired in adiponectin-KO mice compared with wild-type (WT) mice as evaluated by laser Doppler flow method and capillary density analyses. Adenovirus-mediated supplement of adiponectin accelerated angiogenic repair in both adiponectin-KO and WT mice. Intramuscular injection of an adenovirus encoding dominant-negative AMP-activated kinase diminished the improvement in limb perfusion seen in WT mice and abolished the adiponectin-induced enhancement of perfusion. These data indicate that adiponectin can function to stimulate angiogenesis in response to ischemic stress by promoting AMP-activated kinase signaling. Therefore, adiponectin may be useful in the treatment for obesity-related vascular deficiency diseases.
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PMID:Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of amp-activated protein kinase signaling. 1512 26

Obesity-related disorders are associated with the development of ischemic heart disease. Adiponectin is a circulating adipose-derived cytokine that is downregulated in obese individuals and after myocardial infarction. Here, we examine the role of adiponectin in myocardial remodeling in response to acute injury. Ischemia-reperfusion in adiponectin-deficient (APN-KO) mice resulted in increased myocardial infarct size, myocardial apoptosis and tumor necrosis factor (TNF)-alpha expression compared with wild-type mice. Administration of adiponectin diminished infarct size, apoptosis and TNF-alpha production in both APN-KO and wild-type mice. In cultured cardiac cells, adiponectin inhibited apoptosis and TNF-alpha production. Dominant negative AMP-activated protein kinase (AMPK) reversed the inhibitory effects of adiponectin on apoptosis but had no effect on the suppressive effect of adiponectin on TNF-alpha production. Adiponectin induced cyclooxygenase (COX)-2-dependent synthesis of prostaglandin E(2) in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of adiponectin on TNF-alpha production and infarct size. These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2-dependent mechanisms.
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PMID:Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. 1621 Oct 35

Obesity-related disorders are closely associated with the pathogenesis of cardiovascular disease. Adiponectin is a circulating adipose tissue-derived hormone that is down-regulated in obese individuals. Hypoadiponectinemia has been identified as an independent risk factor for type 2 diabetes, coronary artery disease, and hypertension, and experimental studies show that adiponectin plays a protective role in the development of insulin resistance, atherosclerosis, and inflammation. More recent findings have shown that adiponectin directly affects signaling in myocardial cells and exerts beneficial actions on the heart after pressure overload and ischemia-reperfusion injury. This review focuses on the role of adiponectin in the regulation of myocardial remodeling and acute cardiac injury.
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PMID:Cardioprotection by adiponectin. 1678 46

Adiponectin is a circulating cytokine with important cardioprotective effects. Plasma adiponectin levels are significantly reduced in patients with insulin resistance and type II diabetes mellitus and cardiovascular disease. Although adiponectin is primarily synthesized by adipocytes, new studies reveal that adiponectin is secreted by other cell types, including cardiomyocytes. Control of adiponectin gene expression in heart and microvasculature is poorly understood. We investigated the regulation of adiponectin expression by the transcription factor hypoxia inducible factor-1 (HIF-1) and its role in attenuating cardiac reperfusion injury. HIF-1 regulation of adiponectin was examined by isolating and characterizing the murine adiponectin promoter. HIF-1-dependent activation of the murine adiponectin promoter was verified via electrophoretic mobility shift assays, transient transfection assays, and QPCR. We show for the first time that HIF-1 activation via an siRNA-mediated prolyl 4-hydroxylase-2 gene silencing strategy induced adiponectin mRNA expression in murine microvascular endothelium in vitro (17-fold), intact hearts (22-fold, wild type; 5-fold, obese/diabetic) and white adipose tissue (37-fold, wild-type; 9.6-fold, obese/diabetic). HIF-1-induced adiponectin expression was associated with improved myocardial viability in obese/diabetic mice (32% increase) and preservation of left ventricular function (36% increase in rate pressure product). Our studies suggest that local production of adiponectin by cardiomyocytes/microvascular endothelial cells may regulate cardiac function and indicate a novel strategy for protecting diabetic hearts from ischemia/reperfusion injury.
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PMID:Hypoxia inducible factor-1 upregulates adiponectin in diabetic mouse hearts and attenuates post-ischemic injury. 1828 86

Obesity-linked diseases are associated with suppressed endothelial progenitor cell (EPC) function. Adiponectin is an adipose-derived protein that is downregulated in obese and diabetic subjects. Here, we investigated the effects of adiponectin on EPCs. EPC levels did not increase in adiponectin deficient (APN-KO) in response to hindlimb ischemia. Adenovirus-mediated delivery of adiponectin increased EPC levels in both WT and APN-KO mice. Incubation of human peripheral blood mononuclear cells with adiponectin led to an increase of the number of EPCs. Adiponectin induced EPC differentiation into network structures and served as a chemoattractant in EPC migration assays. These data suggest that hypoadiponectinemia may contribute to the depression of EPC levels that are observed in patients with obesity-related cardiovascular disorders.
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PMID:Adiponectin promotes endothelial progenitor cell number and function. 1842 3

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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PMID:Protective vascular and myocardial effects of adiponectin. 1902 92

Adiponectin (APN), a circulating adipose-derived hormone regulating inflammation and energy metabolism, has beneficial actions on cardio- and cerebrovascular disorders. Hypoadiponectinemia is associated with ischemic cerebrovascular disease, however, little is known about the cerebroprotective action of APN as well as its molecular mechanisms. In the present study, the role of APN in the pathogenesis of acute cerebral injury was investigated. Rats were divided into three groups: (i) a sham operation group; (ii) an ischemia/reperfusion (I/R) group, rats were subjected to 1 h middle cerebral artery occlusion followed by 23 h reperfusion (I/R); (iii) a APN-treated group, two bolus of 5 microg APN was administered through jugular vein before and after operation. I/R resulted in obvious cerebral infarct size, neurological deficits, and increased expression of endogenous immunoglobin G and matrix metalloproteinase 9, which can be significantly diminished by administration of APN. We also found that APN can significantly inhibited cerebral expression of myeloperoxidase, a distinct indicator of inflammatory cell infiltration, and inflammatory cytokines, interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-8 in response to I/R, suggesting that APN exerts potent anti-inflammatory actions. Furthermore, nuclear factor (NF)-kappaB (p65), a critical transcription factor involved in inflammatory reactions, was observed predominantly located in the nucleus after I/R, whereas APN can obviously inhibit its translocation from cytoplasm into the nucleus. Results of this study demonstrate that APN exerts a potent cerebroprotective function through its anti-inflammatory action, and NF-kappaB (p65) is a key component in this process. APN might be potential molecular targets for ischemic stroke therapy.
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PMID:Adiponectin protects against cerebral ischemia-reperfusion injury through anti-inflammatory action. 1936 80

Adiponectin is a fat-derived plasma protein that has cardioprotective roles in obesity-linked diseases. Because cyclooxygenase 2 (COX-2) is an important modulator of endothelial function, we investigated the possible contribution of COX-2 to adiponectin-mediated vascular responses in a mouse hind limb model of vascular insufficiency. Ischemic insult increased COX-2 expression in endothelial cells of wild-type mice, but this induction was attenuated in adiponectin knockout mice. Ischemia-induced revascularization was impaired in mice in which the Cox-2 gene is deleted in Tie2-Cre-expressing cells. Adenovirus-mediated overexpression of adiponectin enhanced COX-2 expression and revascularization of ischemic limbs in control mice, but not in targeted Cox-2-deficient mice. In cultured endothelial cells, adiponectin protein increased COX-2 expression, and ablation of COX-2 abrogated the adiponectin-stimulated increases in endothelial cell migration, differentiation, and survival. Ablation of calreticulin (CRT) or its adaptor protein CD91 diminished adiponectin-stimulated COX-2 expression and endothelial cell responses. These observations provide evidence that adiponectin promotes endothelial cell function through CRT/CD91-mediated increases in COX-2 signaling. Thus, disruption of the adiponectin-COX-2 regulatory axis in endothelial cells could participate in the pathogenesis of obesity-related vascular diseases.
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PMID:Adiponectin promotes revascularization of ischemic muscle through a cyclooxygenase 2-dependent mechanism. 1939 82

Angiogenic cell therapy with the transplantation of endothelial progenitor cells (EPC) or bone marrow mononuclear cells (BM-MNC) receives considerable attention as an approach to revascularize ischemic tissues. Adiponectin is a circulating hormone produced by the apM1 gene in adipocytes. Adiponectin modulates lipid metabolism and obesity, and it was recently found to promote physiological angiogenesis in response to ischemia. Patients with multiple cardiovascular disease risk factors or myocardial infarction may benefit from progenitor cell therapy, but they display depressed adiponectinemia. We hypothesized that adiponectin stimulation of transplanted cells is critical for their pro-angiogenic function. We aimed to establish whether adiponectinemia in the cell donor or in the cell recipient determines the success of pro-angiogenic cell therapy. In vitro, we found that conditioned media derived from wild-type adipocytes (adipo-CM) or purified adiponectin strongly enhanced BM-MNC survival and proliferation and stimulated EPC differentiation, whereas adipo-CM from apM1-/- adipocytes was one-half less effective. On the other hand, wild-type and apM1-/- BM-MNC displayed similar resistance to apoptosis and proliferation rates. In vivo, wild-type, and apM1-/- BM-MNC induced similar angiogenic reactions in wild-type ischemic hindlimbs. In contrast, wild-type BM-MNC had much diminished effects in apM1-/- ischemic hindlimbs. We concluded that adiponectin enhances BM-MNC survival and proliferation, and adiponectinemia in the cell therapy recipient is essential for the pro-angiogenic benefits of cell therapy. These observations imply that progenitor cell transplantation might only induce angiogenesis in patients with high adiponectinemia.
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PMID:Adiponectinemia controls pro-angiogenic cell therapy. 1978 8

In this review, we focus on the role of adiponectin as a cardioprotective agent in several pathological heart conditions. Obesity is closely associated with Type 2 diabetes, hypertension and heart disease. Adiponectin is an adipose tissue-derived hormone whose concentration is downregulated in subjects with obesity-related diseases. Hypoadiponectinemia has been identified as an independent risk factor for Type 2 diabetes, coronary artery disease, acute coronary syndrome and hypertension. More recent experimental findings have shown that adiponectin directly affects signaling in cardiac myocytes and has beneficial effects on several pathological heart conditions, including cardiac hypertrophy and myocardial infarction. The favorable effects of adiponectin are associated with attenuated inflammatory response, decreased myocyte death, decreased hypertrophic response, maintained ischemia-induced angiogenesis and reduced interstitial fibrosis. Therefore, adiponectin could represent a molecular target for treating obesity-linked cardiac diseases.
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PMID:Potential of adiponectin as a cardioprotective agent. 1980 85


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