Coronary C-reactive protein distribution: its relation to development of atherosclerosis
Introduction
C-reactive protein (CRP) is a constituent of the blood that increases dramatically in concentration in the presence of various diseases. It was first identified in the sera of patients with pneumonia and received its name because of its precipitation with the C-polysaccharide of the pneumococcus [1]. Serum CRP levels have been found to rise in patients with most forms of infectious disease, with non-infective inflammatory processes, with tissue necrosis and with malignant neoplasms [2], [3]. CRP is synthesized and secreted by hepatocytes within hours of an injury or of the onset of inflammation [2]. It is now categorized as an acute-phase reactant, and the detection of CRP levels in serum is widely used as a sensitive indicator of the presence of inflammation or of tissue injury.
Raised serum CRP levels have been found recently in patients with both acute myocardial infarction [4] and unstable angina [5]. The concentration of CRP in patients with angina pectoris was positively correlated with the subsequent incidence of myocardial infarction or sudden coronary death [6], [7], [8]. The base-line plasma concentration of CRP in apparently healthy men is reported to predict the risk of future myocardial infarction, stroke or coronary heart disease death [9], [10].
The function of CRP is not fully understood. It binds to a wide variety of substances, such as microbial polysaccharides [11], phosphatidylcholine [12] and damaged cell membranes [13], [14]. CRP also enhances the activity of phagocytic cells [2] and activates the classical complement pathway commencing at C1q[15]. Of more interest with regard to atherosclerosis, the aggregated CRP can selectively bind to low-density lipoproteins (LDL) in vitro [16], which may possibly be a factor in the pathogenesis of atherosclerosis.
Whether CRP binds LDL in atherosclerotic lesion is not known. CRP has been extracted from human aortic atherosclerotic lesions [17]. But immunohistochemical investigations of the anatomic distribution of CRP in artery walls are few and are inconsistent in their results [18], [19].
This study was designed, therefore, to determine the immunohistochemical distribution of CRP in human coronary arteries and to correlate it with the development of atherosclerosis and with severity of arterial stenosis.
Section snippets
Materials and methods
The details concerning the sources of the coronary arteries, their fixation, and examination and of the morphometric techniques used have been described previously [20].
Briefly, 68 human hearts (43 male and 25 female, ages from 19 to 89) were obtained at autopsy. The causes of death of these subjects were grouped under six headings, namely, coronary heart disease, other cardiovascular diseases, infectious diseases, cancer, other medical causes and suicide/accident. Coronary arteries from these
C-reactive protein distribution
CRP-specific immunofluorescence was not detected in normal human coronary arteries.
CRP immunofluorescence first appeared in thickened intimas and in early plaques. It showed, initially, either as a subendothelial band or else in the form of minute spots or circles in the bases of small plaques (Fig. 1). CRP immunofluorescence grades increased with increasing size of atherosclerotic plaques. It was associated histologically with lipid-laden macrophages, ceroid pigment and cholesterol crystals (
Discussion
CRP does not react in vitro with the membranes of normal cells but binds to damaged cell membranes [13], [14]. The present investigation showed the absence of CRP in walls of normal coronary arteries and its first appearance in thickened coronary intimas just beneath the endothelium. It is apparently the endothelial cells that have changed, with, at the least, their cell membranes being modified at this stage, which implies that initial coronary intimal thickening has an aetiological basis
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