Relationship between activin A level and infarct size in patients with acute myocardial infarction undergoing successful primary coronary intervention
ABSTRACT Activin A, a member of the transforming growth factor-beta cytokine family, has been suggested to have a role in inflammation. We examined the serum level of activin A in patients with acute myocardial infarction (AMI) undergoing successful primary percutaneous coronary intervention (PCI).
The subjects were 30 AMI patients, 20 stable angina pectoris (AP) patients and 20 normal subjects. The serum levels of activin A in AMI patients were measured before PCI and on days 1, 2, 7, and 14.
Activin A levels before PCI in AMI patients (557+/-255 pg/ml) showed a significantly higher value than those in AP patients (364+/-159 pg/ml) and control subjects (316+/-144 pg/ml). Increased serum activin A level before PCI was decreased on day 2, and then gradually re-elevated on days 7 and 14. The serum activin A level before PCI was correlated with log-transformed peak creatine kinase (CK) as a surrogate of infarct size (r=0.48, p=0.008). Stepwise multiple regression analysis demonstrated that the serum activin A level before PCI was an independent predictor of peak CK.
The serum activin A level, increased in AMI, was positively correlated with peak CK and CK-MB levels which are measures of infarction size.
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ABSTRACT: Adipocyte fatty acid binding protein (A-FABP) has been reported to be involved in insulin resistance, lipid metabolism, and atherosclerosis; however, little is known about the effect of medication on the change in circulating A-FABP in human subjects. We evaluated the effects of angiotensin II type 1 receptor blocker (ARB) on arterial stiffness and its association with serum A-FABP in patients with hypertension. Thirty patients newly diagnosed with essential hypertension were treated with olmesartan (20 mg/day), an ARB, for 6 months. Serum levels of A-FABP and high-sensitivity C-reactive protein (hsCRP) were examined and the cardio-ankle vascular index (CAVI), which is a marker of arterial stiffness, was also determined. Serum A-FABP at baseline was significantly correlated with the body mass index (r = 0.45, P = 0.01), homeostasis model assessment as a marker of insulin resistance (r = 0.53, P < 0.01), and systolic blood pressure (r = 0.37, P = 0.047), and tended to be correlated with low-density lipoprotein cholesterol, triglyceride, and CAVI. Olmesartan treatment resulted in a significant decrease in CAVI, serum A-FABP levels, and hsCRP, besides a significant reduction of blood pressure. Multiple regression analysis revealed that the change in CAVI was independently correlated with the change in serum A-FABP. Olmesartan ameliorated arterial stiffness in patients with hypertension, which may be involved in the reduction of serum A-FABP.Heart and Vessels 11/2010; 26(4):408-13. DOI:10.1007/s00380-010-0060-x · 2.11 Impact Factor
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ABSTRACT: Activin A, a member of the transforming growth factor-β superfamily, is stimulated early in inflammation via the Toll-like receptor (TLR) 4 signalling pathway, which is also activated in myocardial ischaemia–reperfusion. Neutralising activin A by treatment with the activin-binding protein, follistatin, reduces inflammation and mortality in several disease models. This study assesses the regulation of activin A and follistatin in a murine myocardial ischaemia–reperfusion model and determines whether exogenous follistatin treatment is protective against injury. Myocardial activin A and follistatin protein levels were elevated following 30 min of ischaemia and 2 h of reperfusion in wild-type mice. Activin A, but not follistatin, gene expression was also up-regulated. Serum activin A did not change significantly, but serum follistatin decreased. These responses to ischaemia–reperfusion were absent in TLR4−/− mice. Pre-treatment with follistatin significantly reduced ischaemia–reperfusion induced myocardial infarction. In mouse neonatal cardiomyocyte cultures, activin A exacerbated, while follistatin reduced, cellular injury after 3 h of hypoxia and 2 h of re-oxygenation. Neither activin A nor follistatin affected hypoxia-reoxygenation induced reactive oxygen species production by these cells. However, activin A reduced cardiomyocyte mitochondrial membrane potential, and follistatin treatment ameliorated the effect of hypoxia-reoxygenation on cardiomyocyte mitochondrial membrane potential. Taken together, these data indicate that myocardial ischaemia–reperfusion, through activation of TLR4 signalling, stimulates local production of activin A, which damages cardiomyocytes independently of increased reactive oxygen species. Blocking activin action by exogenous follistatin reduces this damage.Cytokine 10/2014; 69(2). DOI:10.1016/j.cyto.2014.06.017 · 2.87 Impact Factor
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ABSTRACT: On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucometabolic abnormalities in patients with acute myocardial infarction (MI). Activin A measurement and oral glucose tolerance tests (OGTTs) were performed in patients (n = 115) with acute MI, without previously known diabetes, and repeated after 3 months. Release of activin A and potential anti-inflammatory effects of activin A were measured in human endothelial cells. Activin A effects on insulin secretion and inflammation were tested in human pancreatic islet cells. 1) In patients with acute MI, serum levels of activin A were significantly higher in those with abnormal glucose regulation (AGR) compared with those with normal glucose regulation. Activin A levels were associated with the presence of AGR 3 months later (adjusted odds ratio 5.1 [95% CI 1.73-15.17], P = 0.003). 2) In endothelial cells, glucose enhanced the release of activin A, whereas activin A attenuated the release of interleukin (IL)-8 and enhanced the mRNA levels of the antioxidant metallothionein. 3) In islet cells, activin A attenuated the suppressive effect of inflammatory cytokines on insulin release, counteracted the ability of these inflammatory cytokines to induce mRNA expression of IL-8, and induced the expression of transforming growth factor-β. We found a significant association between activin A and newly detected AGR in patients with acute MI. Our in vitro findings suggest that this association represents a counteracting mechanism to protect against inflammation, hyperglycemia, and oxidative stress.Diabetes 04/2011; 60(5):1544-51. DOI:10.2337/db10-1493 · 8.47 Impact Factor