To establish whether there are differences in monocyte function in patients with high expression levels compared to low expression levels of microRNA *x*.
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
monocyte function by FACS analysis and cytokine measurement after LPS
stimulation. Moreover, we will perform ChIP analysis for epigenetics and
measure gene expression levels in the monocytes.
Secondary outcome
none
Background summary
Worldwide, tobacco use is the most important avoidable cause of cardiovascular
disease. The risk of developing a myocardial infarction (MI) is twice as high
amongst smokers compared to non-smoking individuals. The mechanism by which
cigarette smoke induces atherosclerosis has not been completely unravelled yet,
but many cell types, amongst which circulating monocytes, are reported to be
involved. Monocytes play a key role in the inflammatory immune response to
external agents. Therefore, circulating monocytes might be influenced by
cigarette smoking.
MicroRNAs (miRNAs) are 18 to 25 nucleotides long, noncoding RNAs, that
downregulate gene expression by suppression of messenger RNA (mRNA)
translation.
Recently, in an unpublished study we discovered that microRNA *x* in monocytes
of smoking individuals exhibit either high or low expression levels, whereas
all non-smokers exhibit only low expression levels.
A subsequent study (hereafter referred to as *smoking study*) unrevealed that
expression levels of microRNA *x* are significantly higher in smoking subjects
with atherosclerosis compared to smoking subjects without atherosclerosis.
Therefore, we hypothesize that smoking in individuals with high microRNA *x*
expression levels induces a change in monocyte function thereby promoting
atherosclerosis.
To test our hypothesis we will assess the monocyte function these specific
patients with high expression levels and compare the monocyte function to
patients with low expression levels of microRNA *x*. Since monocyte function
analysis can only be performed in fresh blood samples, we will need to invite
these patients once to the AMC for blood collection.
Study objective
To establish whether there are differences in monocyte function in patients
with high expression levels compared to low expression levels of microRNA *x*.
Study design
case-control study
Study burden and risks
The burden for participants is a venapuncture. The risks are haematomas or mild
bleeding. There is no direct benefit for the participants. However in general
more insight will be created in the molecular basis of cardiovascular disease.
meibergdreef 9
Amsterdam 1105 AZ
NL
meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- smoking
- known calcium score assessed with a coronary CT scan
- known microRNA 'x' levels
Exclusion criteria
Patients in which statin therapy is a necessity according to standard European guidelines.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL48342.018.14 |