Coronary C-reactive protein distribution: its relation to development of atherosclerosis

Abstract

Two hundred and ninety-nine paraffin-embedded human coronary artery sections from 68 autopsies, both male and female and with various causes of death, were examined for distribution of C-reactive protein (CRP) using the indirect immunofluorescence technique and high-resolution confocal microscopy. The results demonstrate, for the first time, the existence of CRP in human coronary arteries, with evidence of CRP deposits being associated with lipids within in the artery walls. Grades of CRP immunoreactivity positively correlate with relative intimal thickness and negatively correlate with relative lumen size. It is suggested, therefore, that CRP may be related to the development of atherosclerosis and that the development of coronary atherosclerosis is associated with a relapsing inflammatory/necrotic process occurring within the coronary intima.

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 C1_q[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.