Serum basic fibroblast growth factor levels in patients with ischemic heart disease

https://doi.org/10.1016/S0167-5273(97)02921-5Get rights and content

Abstract

Background: Being a potent promoter of endothelial and smooth muscle cell proliferation, basic fibroblast growth factor (bFGF) is presumed to play a key role in coronary collateral development and atherogenesis. Purpose: To characterize serum bFGF levels in patients with ischemic heart disease. Methods: The study population consisted of patients with angina (n=33) and after uncomplicated myocardial infarction (n=12). The number of significantly stenosed (≥50%) vessels and angiographic coronary collateral score were noted. Blood was drawn immediately prior to elective coronary angiography in study patients for bFGF levels. Twenty healthy, age-matched subjects served as control for serum bFGF. Results: Serum bFGF levels were undetectable in all 20 control subjects, but were detectable in 15/33 (45%) patients with angina and 3/12 (25%) post-infarction patients, respectively (P=0.002). Serum bFGF levels were detectable in 13/23 (57%) patients with 0- or 1-vessel disease, as compared with 5/22 (23%) patients with 2- or 3-vessel disease (P<0.05). Detectable serum bFGF levels were not in correlation with coronary collateral score (P=1). Conclusions: Serum levels of bFGF are elevated in patients with ischemic heart disease, particularly in those with minimal coronary artery disease. We postulate that detectable serum bFGF levels reflect active atherogenesis rather than myocardial collateral development.

Introduction

Basic fibroblast growth factor (bFGF) is a 18-kDa molecule with widespread tissue distribution, stored primarily in the endothelial basement membrane [1]. Being a potent mitogen of cells of mesenchymal origin, it promotes proliferation of endothelial and smooth muscle cells [1].

Angiogenesis is the key to coronary collateral development in response to myocardial ischemia [2]. Exogenously-administered bFGF has been shown to induce myocardial angiogenesis in different experimental models of myocardial ischemia/infarction 3, 4, 5, 6, 7, thus increasing coronary collateral flow 3, 5, 6, 7. Angiogenesis is also a fundamental process in tumor growth and metastasis [8]. Using an immunoassay for bFGF [9], increased serum and urine levels of bFGF have been reported in patients with different malignancies 10, 11, 12, supposedly due to bFGF production by tumor cells [13]. As a common process to tumor metastasis and myocardial ischemia, one could postulate that angiogenesis in response to myocardial ischemia would result in elevated systemic levels of bFGF.

Atherogenesis is a complex process entailing smooth muscle proliferation and angiogenesis within the vessel wall [14]. Several workers have previously shown that bFGF might be an important participant in atherogenesis 15, 16, 17, 18, 19. As atherosclerosis is a systemic process with widespread involvement, serum bFGF might be elevated in patients with ischemic heart disease and coronary artery atherosclerosis.

The purpose of the present study was to examine whether serum levels of bFGF are detectable in patients with ischemic heart disease, and to evaluate a possible correlation between serum bFGF levels and extent of coronary artery disease and coronary collateral circulation.

Section snippets

Study population

The study protocol was approved by our institutional review board. All patients gave informed consent after the purpose of the study was explained to them.

The study population consisted of 33 patients undergoing elective coronary angiography due to presence of typical anginal pain and 12 patients recovering from uncomplicated acute myocardial infarction (7.2±1.9 days post-infarction). Patients were not required to undergo noninvasive evaluation for ischemia prior to coronary angiography; the

Results

The demographic and clinical characteristics of the three subgroups comprising the study population are presented in Table 1. Patients with angina and minimal coronary artery disease tended to be younger, but there was no difference between the three subgroups in gender or risk factors. There were subtle differences in drug therapy between the subgroups. Among patients in subgroups II and III, patients in subgroup II had a significantly higher history of previous myocardial infarction, but no

Main findings

We found that serum levels of bFGF are elevated in patients with ischemic heart disease. Elevated serum bFGF levels are found more commonly in patients with minimal coronary artery disease, and are not indicative of status of coronary collateral circulation. Among patients recovering from myocardial infarction, in which bFGF is expected to participate not only in formation of collateral circulation, but also in wound repair and healing [4], bFGF is detectable in only a minority of patients.

Possible explanations

As

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