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Abstract: The purpose of this study was to evaluate whether age influences collateral development in patients with coronary artery disease. The extent of collateral development to the area perfused by the infarct-related artery was graded, depending on the degree of opacification of the occluded infarct-related artery. We evaluated the extent of collateral development using coronary cineangiography in 102 patients with an acutely occluded infarct-related coronary artery within 12 h after the onset of the first acute myocardial infarction, and who had a history of long-standing effort angina. Well-developed collateral circulation was observed in 54 (53%) of the patients. The patients were divided into two groups based on their age. The prevalence of well-developed collateral circulation in the younger group (≤64 years, n = 48) was 69% (33 of 48), being significantly (P = 0.003) higher than 39% (21 of 54) in the older group (≥65 years, n = 54). We conclude that in the presence of stimuli for collateral development i.e., long-standing effort angina accompanied by severe coronary stenosis, the age of patients is a key determinant of collateral development.

Abstract: The expression of genes encoding fatty acid utilization enzymes is coordinately downregulated during the development of cardiac hypertrophy and failure. However, molecular mechanisms that mediate this downregulation are unknown. Peroxisome proliferator-activated receptor (PPAR) response elements (PPREs) have been identified in promoters of many genes involved in fatty acid utilization, where they function as positive regulatory elements. PPARs bind to PPREs as heterodimers with retinoid X receptors (RXRs). Primary cardiac myocytes from neonatal rats were transfected with a reporter construct driven by the C promoter of rat acyl-coenzyme A synthetase (ACS) gene. Stimulation with phenylephrine, a potent inducer of hypertrophy, markedly downregulated the activity of this promoter. By use of electrophoretic mobility-shift assays (EMSAs) using PPRE in the rat ACS promoter as a probe, we found a sequence-specific protein–DNA complex in the nuclear extract from adult rat left ventricular (LV) myocardium. Supershift experiments revealed that this complex was immunoreactive for PPARα and RXRα. We compared the activity of this complex in LV nuclear extracts from Dahl salt-sensitive rats (DSs) with hypertension and control age-matched Dahl salt-resistant rats (DRs). Even at the stage of concentric LV hypertrophy with normal systolic function, the activity of the band was markedly diminished in DSs compared with DRs. However, immunoblot analyses showed no difference in LV expression levels of PPARα or RXRα between DSs and DRs. These findings indicate that a nuclear complex of PPARα/RXRα is present in adult rat LV and is markedly downregulated in the hypertrophied LV from DS rats, which may account for the loss of transcriptional activation. The downregulation of this complex precedes LV systolic dysfunction and is mediated at the posttranslational levels.

Abstract: Acidic fibroblast growth factor (FGF) is a potent mitogen that can induce angiogenesis in vivo. We have recently reported a marked increase of basic FGF in the pericardial fluid of patients with severe coronary stenosis and an increase in vascular endothelial growth factor (VEGF) in the pericardial fluid of patients with severe myocardial ischemia. The purpose of this study was to evaluate whether acidic FGF levels in the pericardial fluid are associated with severe myocardial ischemia. Immediately after incision of the pericardium in 48 patients during open-heart surgery, 3–5 ml of pericardial fluid was obtained. Concentrations of basic FGF and VEGF in the pericardial fluid were measured using an enzyme-linked immunosorbent assay (ELISA). The ELISA system for human acidic FGF was newly developed using a rabbit antibovine acidic FGF antibody. The patients were divided into three groups (group A: 13 patients undergoing emergency coronary artery bypass grafting (CABG) for unstable angina; group B: 17 patients undergoing elective CABG for stable angina; group C: 18 patients undergoing nonischemic open-heart surgery). The VEGF level in the pericardial fluid in group A was 68 ± 59 pg/ml, which was significantly higher than 33 ± 9 pg/ml in group B and 31 ± 20 pg/ml in group C (P < 0.05). The concentrations of basic FGF in the pericardial fluid in groups A and B were 722 ± 601 and 773 ± 763 pg/ml, respectively, significantly higher than 263 ± 349 pg/ml in group C. The pericardial acidic FGF level in group A was 4 291 ± 2 336 pg/ml, which was also significantly higher than 2 386 ± 1 048 pg/ml in group B and 2 589 ± 990 pg/ml in group C (P < 0.05). The acidic FGF level correlated well with the level of VEGF (r = 0.61, P < 0.0001). It is concluded that the level of acidic FGF in pericardial fluid is associated with severe myocardial ischemia. This result indicates that the release of acidic FGF from the myocardial tissue into pericardial fluid is closely related to severe myocardial ischemia.