Angiogenesis in myocardial infarction. An acute or chronic process?
BACKGROUND
In the acute phase of myocardial infarction (acute MI) marked endothelial damage occurs within the first 24h following thrombolysis with streptokinase. We investigated whether this is associated with a change in levels of vascular endothelial growth factor (VEGF, possibly marking angiogenesis) in the first 24h post thrombolysis compared to chronic MI patients (defined as MI>3 months previously).


METHODS
We recruited 15 patients (nine male, mean age 59+/-SD 10 years) with first-presentation acute MI, who were given 1.5 million U streptokinase over 1h and aspirin 300mg orally as standard treatment. Plasma samples were taken prior to the start of thrombolysis, followed every 15 min for 1h, at 3h and finally at 24h post-thrombolysis. Baseline levels of measured indices in the acute MI patients were compared to two control groups: (i) 26 chronic MI patients (18 male, mean age 59.9+/-7.0 years); and (ii) 26 apparently healthy controls (17 male, mean age 59.6+/-14.1 years). Plasma VEGF and the soluble form of its receptor Flt-1 (sFlt-1) were measured by ELISA.


RESULTS
Plasma levels of VEGF were significantly higher in patients with a history of chronic MI compared to patients with acute MI (P=0.007) and healthy controls (P=0.002) with similar levels between acute MI patients and healthy controls (P=0.755). Levels of sFlt-1 in the acute (P=0.013) and chronic (P<0.001) MI groups were lower compared to healthy controls. In the first 24h post-thrombolysis in the acute MI group, levels of sFlt-1 changed significantly (P=0.039), but there was no change in levels of VEGF (P=0.207).


CONCLUSIONS
In the first 24h of acute MI, significant changes in levels of VEGF receptor sFlt-1, but not VEGF, are seen. Plasma VEGF and sFlt-1 levels are markedly changed in chronic MI patients, suggesting that the activation of angiogenesis in MI patients may be a delayed response.
D000208:Acute Disease; D000368:Aged; D002908:Chronic Disease; D016228:Endothelial Growth Factors / Q000097:blood; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008222:Lymphokines / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000209:etiology*; D012016:Reference Values; D015912:Thrombolytic Therapy; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1