Increased myocardial prevalence of C‐reactive protein in human coronary heart disease: relation to local endothelial injury and microvessel rarefaction

Abstract

Increased plasma C-reactive protein (CRP) is a biomarker of coronary heart disease (CHD) but its potential roles as a disease participant are not well defined. A key component of CHD is endothelial injury and dysfunction. Here we tested the hypotheses that CRP is detectable in human cardiac specimens and is elevated in patients with CHD, and these changes are related to local endothelial stress and/or microvessel rarefaction. Cardiac LV specimens were collected at autopsy within 4h of death and were classified as normal controls (CTL) or evidence of CHD (w/o MI) (n=12/group). Immunohistochemistry and digital image analyses were used to define discrete regional distributions of CRP in myocyte, coronary artery and microvessel regions. Prevalence of subendocardial microvessels was determined using an anti-CD31 antibody and automated macro. Increased interstitial fibrosis & hypertrophy was seen in CHD. CTL had detectable levels of CRP, which was increased in CHD group (p<0.05). Microvessel prevalence was significantly reduced in CHD myocardium vs. CTL, and rarefaction was inversely correlated to myocardial CRP prevalence (p<0.05). These findings provide evidence that locally produced myocardial CRP is a potential participant of myocardial toxicity and microvascular rarefaction. These observations may also help to explain the strong predictive value of increased blood CRP to CHD progression in humans