Carboxypeptidase N and Creatine Kinase-MB Isoforms in Acute Myocardial Infarction

Abstract

Summary: The aims of our study were to evaluate the plasma Carboxypeptidase N activity in normal subjects and in patients with acute myocardial infarction and to delineate its relationship with creatine kinase-MB isoforms in monitoring of acute myocardial infarction, Carboxypeptidase N being the major determinant of creatine kinase isoform conversion in plasma. The study was carried out in 34 healthy subjects and 19 patients with acute myocardial infarction diagnosed according to the World Health Organization (WHO) criteria in which the blood samples were collected immediately upon admission to the coronary care unit (median time 3.5 hours), every 4 to 6 hours for 24 hours, and every 12 hours until the third day post admission. Carboxypeptidase N activity, total creatine kinase, creatine kinase-MB mass concentration and creatine kinase-MB isoforms were determined in each sample from acute myocardial infarction patients, whereas only Carboxypeptidase N and total creatine kinase activities were assayed in samples from healthy subjects. The results showed a high variability in Carboxypeptidase N values among healthy subjects (median = 220 U/l; interquartile range = 190-247 U/l) and in the first available samples from acute myocardial infarction patients (median = 213 U/l; interquartile range = 197-234 U/l) without significant differences between groups and without a correlation between Carboxypeptidase N and creatine kinase activities either in healthy subjects or in acute myocardial infarction patients; in the latter group, however, a significant correlation (p < 0.01) with creatine kinase-MB calculated on all samples, was observed. In acute myocardial infarction patients Carboxypeptidase N showed time-related variations, reaching the highest levels about 48 h after onset of chest pain. A statistically significant difference in Carboxypeptidase N values (p = 0.0001) was found before and after creatine kinase-MB peak values as well as before and after MB 2 /MB! normalization. Worthy of note is the finding that in two acute myocardial infarction patients presenting MB 2 /MBj ratios lower than the cutoff value (1.5) throughout the period of observation, the baseline values for Carboxypeptidase N were higher than in other patients studied. Our results suggest that the increase of Carboxypeptidase N activity after infarction could be induced by an increase in endogenous substrate concentrations, in particular creatine kinase-MB released from damaged myocardium. Furthermore, high baseline levels of Carboxypeptidase N will reduce the diagnosis efficiency of creatine kinase-MB isoforms in the diagnosis of acute myocardial infarction.

Peptidomics for Cancer Diagnosis: Present and Future

“…A few years ago, van Hensbergen et al showed that in both malignant effusions and intratumoral fluid, as well as in plasma, there is increased aminopeptidase N activity which correlates with tumor load, suggesting that this enzyme may be originating from tumor cells . Similar observations for carboxypeptidase N activity increase in myocardial infarction have also been published by Zaninotto et al Thus, as Villanueva et al suggest, there is a chance that what they see may correlate with exoprotease activities originating from tumors.…”

Direct Tandem Mass Spectrometry Reveals Limitations in Protein Profiling Experiments for Plasma Biomarker Discovery

“…[39][40][41][42][43][44][45] Heightened activity of AMPN has been reported for cancer patients, 46 and CBPN activity is increased after myocardial infarction. 47 The proteins that were identified here also indicate some specificity in the cleavage patterns, i.e., the abundances of the plasma peptides observed here do not mirror the abundant proteins (see Table 2). In this data set, only one fragment was identified from serum albumin.…”

Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

“…Serum levels of CPN2 were not investigated in patients with stroke, but increased concentrations were found in patients with acute myocardial infarction (41). For FXII, studies showed high concentrations in patients with chronic cerebrovascular diseases (42), and FXII inhibition, as well as FXII deficiency improved outcome in experimental IS (45)(46)(47)(48)(49).…”