Hepatocyte growth factor production may be related to the inflammatory response in patients with acute myocardial infarction.
ABSTRACT Hepatocyte growth factor (HGF) is a well-known powerful proliferative factor of vascular endothelial cells and it has been reported that plasma HGF concentrations are increased in acute myocardial infarction (AMI), although the mechanisms are not yet well delineated. Serum HGF levels and C-reactive protein (CRP) were measured in 22 patients with unstable angina pectoris (UAP) (15 males, 7 females; class IIb or IIIb of the Braunwald classification), 60 patients with AMI (37 males, 23 females; average time from the onset of symptoms to admission 4.6+/-0.7h, range, 0.5-12h), and 20 normal subjects. Immediate angioplasties were performed in 51 patients with AMI, and the time course of the HGF levels were measured in 31 patients among them. Heparin dramatically increased the HGF level and it declined to the normal range 18h after heparin injection. Blood samples were taken before heparin treatment, or at least 24h after. Serum HGF levels on admission was significantly increased in UAP (mean+/-SE: 0.30+/-0.03ng/ml, p<0.01), and AMI (0.27+/-0.02ng/ml, p<0.01) compared with the normal subjects (0.19+/-0.01 ng/ml). Even in the early stage (within 3 h of onset of symptoms to admission, average time was 1.8+/-0.1 h), serum HGF levels were already elevated (0.25+/-0.02 ng/ml, p<0.05). There was no significant difference between the HGF levels in UAP and AMI. Fifty-one of the 60 patients with AMI underwent immediate percutaneous transluminal coronary angioplasty and blood samples were obtained from 31 of them on days 7, 14, and 21 after MI. Serum HGF levels peaked on day 7 (0.34+/-0.04ng/ml, p<0.01) and there was a weak relationship between peak creatine kinase and serum HGF levels at that time. A statistically significant correlation was found between peak CRP and serum HGF levels on day 7 (r=0.62: p<0.001). Serum HGF levels decreased to nearly normal by day 21 (0.22+/-0.01 ng/ml). The study shows that serum HGF levels during the early stage of AMI increased significantly and peaked by day 7 after the onset, at which time there was a strong correlation with peak CRP levels. These data suggest that HGF production may be related to the inflammatory response in AMI.
- SourceAvailable from: Giuseppina Caligiuri[show abstract] [hide abstract]
ABSTRACT: A growing body of evidence suggests a role for inflammation in acute coronary syndromes. The aim of this study was to assess the role of proinflammatory cytokines, their time course, and their association with prognosis in unstable angina. We studied 43 patients aged 62+/-8 years admitted to our coronary care unit for Braunwald class IIIB unstable angina. In each patient, serum levels of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6) (which represent sensitive markers of biologically active IL-1beta and tumor necrosis factor-alpha levels, respectively), and troponin T were measured at entry and 48 hours after admission. Troponin T-positive patients were excluded. Patients were divided a posteriori into 2 groups according to their in-hospital outcome: group 1 comprised 17 patients with an uneventful course, and group 2 comprised 26 patients with a complicated in-hospital course. In group 1, mean IL-1Ra decreased at 48 hours by 12%, and IL-6 diminished at 48 hours by 13%. In group 2, IL-1Ra and IL-6 entry levels were higher than in group 1 and increased respectively by 37% and 57% at 48 hours (P<0.01). These findings indicate that although they receive the same medical therapy as patients who do not experience an in-hospital event, patients with unstable angina and with complicated in-hospital courses have higher cytokine levels on admission. A fall in IL-1Ra and IL-6 48 hours after admission was associated with an uneventful course and their increase with a complicated hospital course. These findings may suggest novel therapeutic approaches to patients with unstable angina.Circulation 05/1999; 99(16):2079-84. · 15.20 Impact Factor
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ABSTRACT: Hepatocyte growth factor (HGF) functions as a hepatotrophic and renotrophic factor for regeneration of the liver and kidney. When 1 ng/ml of interleukin-1 alpha (IL-1 alpha) or interleukin-1 beta (IL-1 beta) was added to cultures of human skin fibroblasts, the production of HGF was 5-6 fold higher than levels in the controls. HGF mRNA level in the cells was increased to 4-fold higher levels at 6 h after exposure to IL-1 alpha. Tumor necrosis factor-alpha and interferon-gamma but no other cytokine tested had slightly stimulatory effects on HGF production. The tumor promoter, tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the stimulatory effect of IL-1 alpha and IL-1 beta on the production of HGF. The stimulatory effect of both IL-1 alpha and IL-1 beta and the synergistical stimulation with TPA were completely abrogated by 10 ng/ml TGF-beta 1 or 1 microM dexamethasone. These results suggest that IL-1 alpha and IL-1 beta are positive regulators for expression of the HGF gene and are likely have a role in regeneration of tissues following the occurrence of inflammatory diseases.Biochemical and Biophysical Research Communications 11/1992; 188(1):235-43. · 2.41 Impact Factor
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ABSTRACT: We measured serum hepatocyte growth factor (HGF) in patients with acute myocardial infarction, angina pectoris, and other heart diseases. In patients with acute myocardial infarction, blood was collected at the time of admission. Serum HGF was elevated within 3 hours in 8 of 10 patients (80%) with acute myocardial infarction after onset of chest pain (9.4 +/- 3.2 ng/mL, mean +/- SEM, values in normal subjects <0.39 ng/mL). Mean value of serum HGF was 11.0 +/-2.6 ng.mL (n=11) in patients who admitted to the hospital between 6 and 9 hours and 13.1 +/- 5.7 ng.mL between 12 and 24 hours after onset. Elevated HGF levels were significantly more frequent than those of creatine kinase within 3 hours, and elevated levels correlated well with those of serum creatine kinase at 6-9 hours after onset of acute myocardial infarction. No increase in serum HGF value was found in patients with angina pectoris or other heart diseases. Thus, measurement of HGF is a sensitive method for early diagnosis of acute myocardial infarction.Biochemical and Biophysical Research Communications 04/1996; 221(2):391-5. · 2.41 Impact Factor