Enhanced Expression of the S100A8/A9 Complex in Acute Myocardial Infarction Patients

Abstract

Background: S100A8/A9 complex (S100A8/A9) is expressed in activated human neutrophils and macrophages. Enhanced expression of S100A8/A9 in atherosclerotic plaque of patients with unstable angina pectoris (UAP) has been demonstrated, but its profile in acute myocardial infarction (AMI) has not been clarified. Methods and Results:Serum S100A8/A9 levels were serially measured in patients with AMI (n=55) and UAP (n=16) during the acute period. The expression of S100A8/A9 was examined immunohistochemically in the infarcted myocardium of 7 autopsied patients with AMI. Serum S100A8/A9 levels on the 1st day were 1,118±115 (SE) ng/ml in AMI patients as compared with 787±147 ng/ml in UAP patients. On days 3-5, serum S100A8/A9 levels in AMI patients reached a peak value and were significantly higher than the values in UAP patients (1,690±144 ng/ml vs 844±100 ng/ml; P<0.0001). In AMI patients, peak S100A8/A9 levels positively correlated with peak white blood cell and neutrophil counts, and peak creatine kinase-MB and peak C-reactive protein levels. Double immunostaining revealed that S100A8/A9 was specifically expressed in neutrophils and macrophages infiltrating the infarcted myocardium.Conclusions: S100A8/A9 is implicated in the pathophysiology of AMI and may be an additional biomarker of the local inflammatory response following AMI. (Circ J 2010; 74: 741 - 748)

Calgranulins May Contribute Vascular Protection In Atherogenesis

“…46 In acute MI patients, serum S100A8/A9 levels positively correlate with peak neutrophil count and activated neutrophils infiltrating border regions of infarcts in early acute lesions, and macrophages, represent possible sources. 43 S100A12 is elevated in sera from patients with carotid atherosclerosis, 42,47 possibly released from ruptured plaque 42 and is even more prominent in sudden cardiac death patients with diabetes. 48 S100A12 has been found in macrophages 42 and smooth muscle cells (SMC) in ruptured plaque and localized to the medial layer at sites of degeneration and dissection of thoracic aneurysms.…”

Plasma S100A8/A9 Correlates With Blood Neutrophil Counts, Traditional Risk Factors, and Cardiovascular Disease in Middle-Aged Healthy Individuals

“…15,16 Plasma S100A8/A9 levels are highly elevated in MI compared with stable and unstable angina, and S100A8/A9 correlates with the incidence of recurrent CV events in MI survivors. 16,17 The purpose of our study was to elucidate whether plasma S100A8, S100A9, and S100A8/A9 reflect the severity of existing carotid artery disease and correlate with long-term CV risk in apparently healthy middle-aged individuals.…”

“…15,16 Plasma S100A8/A9 levels are highly elevated in MI compared with stable and unstable angina, and S100A8/A9 correlates with the incidence of recurrent CV events in MI survivors. 16,17 The purpose of our study was to elucidate whether plasma S100A8, S100A9, and S100A8/A9 reflect the severity of existing carotid artery disease and correlate with long-term CV risk in apparently healthy middle-aged individuals. We measured baseline concentrations of S100A8, S100A9, and S100A8/A9 in 664 subjects with no previous history of CVD and examined their correlations with circulating leukocyte populations, smoking, diabetes mellitus, body mass index (BMI), blood pressure, plasma lipids, glycemic control, plasma cytokines, carotid intima-media thickness (IMT), and IM area, as well as with the risk for incident CV events during a median followup period of 16.2 years.…”

“…11 In patients with MI, S100A9 mRNA transcripts are increased in circulating platelets 14 and S100A8/ A9-positive neutrophils and macrophages infiltrate both the occluding thrombus and the infarcted myocardium. 15,16 S100A8/A9 is released early into the systemic circulation during the acute coronary event and correlates with markers of myocardial injury and neutrophil counts. 15,16 In MI survivors, elevated S100A8/A9 levels at 30 days postevent are associated with a higher risk for recurrent CV events within the next 30-day period.…”

S100A8/A9 Complex

“…In this issue of the Journal, Katashima et al report enhanced expression of the S100A8/A9 complex in acute MI patients. 7 In serial measurements, S100A8/A9 serum levels were consistently 1.5-to 2.0-fold higher in patients presenting with acute MI (n=55) compared with those presenting with unstable angina pectoris (n=16). Immunohistochemical analysis also demonstrated that infiltrating neutrophils and macrophages express high levels of S100A8/A9 at the site of acute MI.…”