The role of inflammation in cardiac and vascular remodelling

Leiden Repository

The role of inflammation in cardiac and vascular remodelling

Type: Doctoral Thesis
Title: The role of inflammation in cardiac and vascular remodelling
Author: Jong, R.C.M. de
Issue Date: 2019-01-31
Keywords: Vascular remodelling
Cardiac remodelling
Myocardial infarction
Inflammation
Epigenetics
MicroRNA
Phosphorylcholine
PCAF
Annexin A5
Abstract: Cardiovascular disease (CVD) is the collective term for diseases that involve the heart or circulation and CVDs are a major cause of mortality and morbidity worldwide. The aim of thesis was to investigate the role of inflammation in CVD related cardiac and vascular remodelling, which may lead to potential therapeutic agents. We investigated the therapeutic potential of antibodies directed against phosphorylcholine (PC), an endogenous ligand capable of triggering the innate immune system, which is expressed by apoptotic cells and oxidized LDL, in mouse models for myocardial infarction (MI). We found that treatment with anti-PC antibodies reduces adverse cardiac remodelling after both permanent MI as myocardial ischemia reperfusion (MI-R) injury. Furthermore, we found that treatment with annexin A5 also reduces adverse cardiac remodelling after MI-R injury. Interestingly, both anti-PC as annexin A5 treatment reduced the post MI inflammatory response. Next, we investigated the role of PCAF, an inflammatory related epigenetic factor, in vascular remodelling. We found that PCAF deficiency and treatment with a PCAF inhibitor reduces adverse vascular remodelling. Finally, we investigated the role of microRNAs, small RNA molecules that can affect expression of many different gene simultaneously, in vascular remodelling. We show that inhibition of microRNA-495 reduces adverse vascular remodelling.
Promotor: Supervisor: Quax P.H.A., Jukema J.W. Co-Supervisor: Vries M.R. de
Faculty: Faculty of Medicine, Leiden Uiversity Medical Center (LUMC)
University: Leiden University
Uri: urn:isbn:9789402813098
Handle: http://hdl.handle.net/1887/68468
 

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