Endogenous C1-inhibitor production and expression in the heart after acute myocardial infarction.

Abstract

BACKGROUND:

Complement activation contributes significantly to inflammation-related damage in the heart after acute myocardial infarction. Knowledge on factors that regulate postinfraction complement activation is incomplete however. In this study, we investigated whether endogenous C1-inhibitor, a well-known inhibitor of complement activation, is expressed in the heart after acute myocardial infarction.

MATERIALS AND METHODS:

C1-inhibitor and complement activation products C3d and C4d were analyzed immunohistochemically in the hearts of patients who died at different time intervals after acute myocardial infarction (n=28) and of control patients (n=8). To determine putative local C1-inhibitor production, cardiac transcript levels of the C1-inhibitor-encoding gene serping1 were determined in rats after induction of acute myocardial infarction (microarray). Additionally, C1-inhibitor expression was analyzed (fluorescence microscopy) in human endothelial cells and rat cardiomyoblasts in vitro.

RESULTS:

C1-inhibitor was found predominantly in and on jeopardized cardiomyocytes in necrotic infarct cores between 12h and 5days old. C1-inhibitor protein expression coincided in time and colocalized with C3d and C4d. In the rat heart, serping1 transcript levels were increased from 2h up until 7days after acute myocardial infarction. Both endothelial cells and cardiomyoblasts showed increased intracellular expression of C1-inhibitor in response to ischemia in vitro (n=4).

CONCLUSIONS:

These observations suggest that endogenous C1-inhibitor is likely involved in the regulation of complement activity in the myocardium following acute myocardial infarction. Observations in rat and in vitro suggest that C1-inhibitor is produced locally in the heart after acute myocardial infarction.

• Authors: Reindert W Emmens, Umit Baylan, Lynda J M Juffermans, Rashmi V Karia, Bauke Ylstra, Diana Wouters, Sacha Zeerleder, Suat Simsek, Marieke van Ham, Hans W M Niessen, Paul A J Krijnen
• Journal: Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology (Cardiovasc Pathol) 2016 Jan-Feb Vol. 25 Issue 1 Pg. 33-9 ISSN: 1879-1336 [Electronic] United States
• PMID: 26476955 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Complement C1 Inactivator Proteins
• Complement C1 Inhibitor Protein
• Peptide Fragments
• RNA, Messenger
• SERPING1 protein, human
• Complement C3d
• Complement C4b
• complement C4d

Topics

• Animals
• Cell Line
• Complement C1 Inactivator Proteins (metabolism)
• Complement C1 Inhibitor Protein
• Complement C3d (metabolism)
• Complement C4b (metabolism)
• Disease Models, Animal
• Human Umbilical Vein Endothelial Cells (metabolism, pathology)
• Humans
• Male
• Myoblasts, Cardiac (metabolism, pathology)
• Myocardial Infarction (genetics, metabolism, pathology)
• Myocardium (metabolism, pathology)
• Necrosis
• Peptide Fragments (metabolism)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Wistar
• Retrospective Studies
• Time Factors
• Up-Regulation