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

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• 作者：Reindert W. Emmens^a ; ^e ; ^f ; ^{r.emmens@vumc.nl" class="auth_mail" title="E-mail the corresponding author} ; Umit Baylan^a ; ^e ; ^{u.baylan@vumc.nl" class="auth_mail" title="E-mail the corresponding author} ; Lynda J.M. Juffermans^b ; ^e ; ^g ; ^{ljm.juffermans@vumc.nl" class="auth_mail" title="E-mail the corresponding author} ; Rashmi V. Karia^a ; ^{rashmi.v.karia@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Bauke Ylstra^a ; ^{b.ylstra@vumc.nl" class="auth_mail" title="E-mail the corresponding author} ; Diana Wouters^f ; ^{d.wouters@sanquin.nl" class="auth_mail" title="E-mail the corresponding author} ; Sacha Zeerleder^f ; ^h ; ^{s.s.zeerleder@amc.uva.nl" class="auth_mail" title="E-mail the corresponding author} ; Suat Simsek^c ; ⁱ ; ^{s.simsek@mca.nl" class="auth_mail" title="E-mail the corresponding author} ; Marieke van Ham^f ; ^{m.vanham@sanquin.nl" class="auth_mail" title="E-mail the corresponding author} ; Hans W.M. Niessen^a ; ^d ; ^e ; ^{jwm.niessen@vumc.nl" class="auth_mail" title="E-mail the corresponding author} ; Paul A.J. Krijnen^a ; ^e ; ^{paj.krijnen@vumc.nl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Acute myocardial infarction ; Ischemia ; Complement ; C1-inhibitor
• 刊名：Cardiovascular Pathology
• 出版年：2016
• 出版时间：January-February 2016
• 年：2016
• 卷：25
• 期：1
• 页码：33-39
• 全文大小：1164 K

文摘

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 12 h and 5 days old. C1-inhibitor protein expression coincided in time and colocalized with C3d and C4d. In the rat heart, serping1 transcript levels were increased from 2 h up until 7 days 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.