1. Elevated Circulating Levels of Inflammatory Markers in
Patients with Acute Coronary Syndrome
Hamad Al Shahi, Kazunori Shimada, Katsumi Miyauchi, Takuma Yoshihara, Eiryu Sai, Tomoyuki Shiozawa,
Tatsuro Aikawa, Shohei Ouchi, Tetsuro Miyazaki, Hiroyuki Daida.
Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine.
Background
Expression of IL-23A , IL-27, IL-33 and IL-37
Clinical Characteristics
Acute coronary syndrome (ACS) usually occur in response to inflammation, plaque rupture, subsequent thrombosis, and eventually progressive obstruction.
Armstrong et al. Circulation. 2006;113:72-75
Atherosclerosis is recognized as a chronic inflammatory disease in patients with the atherosclerotic process and increased levels of systemic inflammatory markers are expected.
Shimada K. Circulation Journal. 2009;73:
Characteristics
CAD (n = 50)
ACS (n = 20)
Age (years)
70 ± 7
65 ± 11
Sex (male/female)
40/10
19/1
BMI, kg/m2
24 ± 3
23 ± 2
Family history, 𝑛 (%)
13 (26)
6 (30)
Hypertension, 𝑛 (%)
38 (76)
12 (60)
Diabetes, 𝑛 (%)
21 (42)
5 (25)
Smoking, 𝑛 (%)
35 (70)
13 (65)
Systolic BP-mm Hg
138 ± 19
139 ± 25
Diastolic BP -mm Hg
78 ± 12
81 ± 17
Laboratory measurements
TC (mg/dl)
165 ± 28
189 ± 44*
TG (mg/dl)
120 ± 48
155 ± 106*
LDL-cholesterol (mg/dl)
96 ± 26
114 ± 34*
HDL-cholesterol (mg/dl)
45 ± 13
48 ± 10
Creatinine (mg/dl)
0.84 ± 0.22
0.77 ± 0.26
HbA1c %
5.8 ± 0.7
5.7 ± 0.8
Hs-CRP (mg/dl)
0.12 ± 0.16
0.13 ± 0.07
BNP (pg/ml)
57 ± 72
89 ± 121
Medications, 𝑛 (%)
Antiplatelet
50 (100)
20 (100)
beta-blocker
24 (48)
ACEI/ARB
27 (54)
11 (55)
CCB
23 (46)
Statin
32 (64)
Aim of the Study
The aim of this study was to evaluate inflammatory cytokines and chemokine such as tumor necrosis factor alpha (TNF-α), Interleukin (IL)-6, IL-10, IL-18, IL-18 binding protein (IL-18BP), IL-23A, IL-27, IL-33, IL-37 and monocyte chemoattractant protein (MCP-1) expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with either ACS or stable coronary artery disease (CAD).
Expression of MCP-1, IL-18 and IL-18BP
Study Design
A total of 70 consecutive patients (mean age 69 years), were enrolled in this study. The participants were divided into two groups, stable CAD group (n=50) and ACS group (n= 20). ACS was defined as a spectrum of CAD that included acute myocardial infarction (AMI) and unstable angina pectoris (UAP).
Exclusion criteria were patients with previous history of ACS, autoimmune, neoplastic, liver, and hematological diseases. Laboratory measurements of patients with estimated glomerular filtration rate (eGFR) ≤30ml/min/1.73m2 and C-reactive protein (CRP) ≥1.0 mg/dl were also excluded.
The data are given as the mean ± SD. CAD: coronary artery disease; ACS: Acute coronary syndromes; BMI: Body mass index; BP: blood pressure; TC: total cholesterol; TG: triglycerides; LDL: low-density lipoprotein; HDL: high-density lipoprotein; Hb: haemoglobin; Hs-CRP: High-sensitivity C-reactive protein; BNP: Brain natriuretic peptide; ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; CCB: calcium channel blocker.
* 𝑃 <0.05.
*𝑃 <0.05, ** 𝑃 <0.01, *** 𝑃 <0.001
Discussion
This study showed that the expression levels of the pro-and anti-inflammatory mediators were dramatically increased in patients with ACS compared with CAD patients.
The expressions levels of TNF-α, IL-6, IL-10, IL-23A, IL-27 and IL-37 were significantly higher in the ACS group compared with CAD group (P <0.05). In contrast, the expression levels of IL-33 in the ACS group showed a significant lower than the CAD group (P <0.05).
Methods
Results
Isolation of PBMCs from the whole blood. Followed by isolation of mRNA.
cDNA synthesis
Expression of inflammatory cytokine by using qPCR
Expression of TNF-α , IL-6 and IL-10
Limitation
There are some limitations in this study. First is the small number of subjects. Second limitation is this study relied on a single baseline blood sample and thus cannot take into account any variation of inflammatory markers that may change over time.
Conclusion
This study showed that circulating levels of pro-inflammatory cytokines and chemokine might be involved in the triggering stage of ACS. Further studies are needed to confirm their precise role in the pathogenesis of ACS.
Conflict of interest
No conflict of interest relevant to this study is reported.