Abstract
BackgroundAtherosclerosis is a multifactorial disorder of the heart vessels that develops over decades, coupling inflammatory mechanisms and elevated total cholesterol levels under the influence of genetic and environmental factors. Without effective intervention, atherosclerosis consequently causes coronary heart disease (CHD), which leads to increased risk of sudden death.Polymorphonuclear neutrophils play a pivotal role in inflammation and atherogenesis. Human neutrophil peptides (HNPs) or alpha (α)-defensins are cysteine-rich cation polypeptides that are produced and released from activated polymorphonuclear neutrophil granules during septic inflammation and acute coronary vascular disorders. HNPs cause endothelial cell dysfunction during early atherogenesis. In this cross-sectional study, control, hyperlipidemia and CHD groups were representative as atherosclerosis development and CHD complications. We aimed to assess the correlation between α-defensin expression and the development of CHD, and whether it was a useful predictive indicator for CHD risk.MethodsFirst, DNA microarray analysis was performed on peripheral blood mononuclear cells (PBMCs) from Thai control, hyperlipidemia and CHD male patients (n = 7). Gene expression profiling revealed eight up-regulated genes common between hyperlipidemia and CHD patients, but not controls. We sought to verify and compare α-defensin expression among the groups using: 1) real-time quantitative RT-PCR (qRT-PCR) to determine α-defensin mRNA expression (n = 10), and 2) enzyme-linked immunosorbent assay to determine plasma HNP 1–3 levels (n = 17). Statistically significant differences and correlations between groups were determined by the Mann–Whitney U test or the Kruskal–Wallis test, and the Rho-Spearman correlation, respectively.ResultsWe found that α-defensin mRNA expression increased (mean 2-fold change) in the hyperlipidemia (p = 0.043) and CHD patients (p = 0.05) compared with the controls. CHD development moderately correlated with α-defensin mRNA expression (r = 0.429, p = 0.023) and with plasma HNP 1–3 levels (r = 0.486, p = 0.000).ConclusionsIncreased α-defensin expression is a potential inflammatory marker that may predict the risk of CHD development in Thai hyperlipidemia patients.
Highlights
Atherosclerosis is a multifactorial disorder of the heart vessels that develops over decades, coupling inflammatory mechanisms and elevated total cholesterol levels under the influence of genetic and environmental factors
The healthy and hyperlipidemia patients did not differ in age, whereas the coronary heart disease (CHD) patients were significantly older compared with the control and hyperlipidemia groups
Our findings revealed that α-defensin mRNA expression in hyperlipidemia (p = 0.043) and bypass graft surgery (p = 0.05) patients was increased compared with controls
Summary
Atherosclerosis is a multifactorial disorder of the heart vessels that develops over decades, coupling inflammatory mechanisms and elevated total cholesterol levels under the influence of genetic and environmental factors. Atherosclerosis develops under the influence of genetic and environmental factors It is a chronic inflammatory disorder of the vessel wall, where both innate and adaptive immune responses influence disease progression [1]. This involves: impairment of endothelial cell (EC) function; accumulation of cholesterol in subendothelial macrophage-derived foam cells; adherence and recruitment of leukocytes into the arterial wall; proliferation and migration of smooth muscle cells into the intima; activation and aggregation of platelets; T cell activation; and production of inflammatory cytokines [2]. Monocytes differentiate into macrophages in the presence of macrophage colony-stimulating factor (M-CSF) produced in lesions by ECs and smooth muscle cells This is a crucial step in atherogenesis and is accompanied by upregulation of innate immune receptors required for phagocytosis and induction of inflammatory processes [6]
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