Review articleInvolvement of circulating inflammatory factors in prognosis and risk of cardiovascular disease
Introduction
Inflammation is a protective response aligned with the release of inflammatory factors from immune cells against pathogens, which is associated with tissue damage [1,2]. As pathological processes, inflammatory pathways are effective in the initiation and progression of disease [1], whereby inflammatory factors can act as peripheral clinical markers for vascular wall inflammation [3]. Furthermore, imbalance in the immune response via increase in the damage of myocardium can trigger initiation, progression, and eventual complications of atherosclerosis [1,4,5]. Atherosclerosis results from an increase in inflammatory factors such as acute phase proteins and cytokines, and subsequent changes in endothelium of coronary arteries, and can act as a risk factor for cardiovascular disease (CVD) [6]. CVD is a widespread cause of mortality in which various contributors entailing elevated cholesterol levels, insulin resistance, diabetes, obesity, and inflammatory diseases are involved as risk factors through developing atherosclerotic lesions [4]. Biologic activities of inflammatory factors in CVD can be effective in plaque formation and rupture, endothelial dysfunction, and eventually coronary thrombosis [7]. Regarding the link between atherosclerosis factors with its stages, it seems that inflammatory factors may directly increase the risk of CVD and myocardial infarction (MI) or stroke. Given the significant role of inflammatory processes in CVD pathophysiology, we aimed to assess changes in the expression of inflammatory factors in CVD, and, secondarily, the possibility of their role as prognostic factors in this disease.
Section snippets
Mechanisms of inflammation in CVD
Production of inflammatory cytokines and acute phase proteins following immune response in CVD patients can act as a biochemical risk factor in atherosclerosis development [4]. Since atherosclerosis plays an important role in CVD pathological process [3], knowledge of mechanisms and biological activities of inflammatory factors such as interleukin 6 (IL-6), C-reactive protein (CRP), fibrinogen, tumor necrosis factor alpha (TNF-α), and glycoprotein acetylation (GlycA) that are involved in
Association between inflammatory factors and endothelial dysfunction
ECs forming internal lumen of the vasculature are major players in controlling vascular tone such as regulating vasodilation and vasoconstriction, growth of vascular smooth muscle cells, inflammation, hemostasis, and maintaining a proper blood supply to tissues [2,76]. ECs dysfunction is a leading cause of vascular diseases such as atherosclerosis and CVD [2], and inflammation is one of causal factors in ECs damages that can trigger ECs dysfunction [2,76]. As a major factor of inflammation,
Role of inflammatory factors in thrombosis
As a major component of homeostasis, platelets have a crucial role in thrombosis via secretion of factors including inflammatory cytokines, platelet-derived growth factors, and thrombin [97]. Since thrombosis takes place after activation of immune system and inflammation, it has been observed that platelets contribute to the induction of inflammation through interaction with leukocytes as well as their trafficking and migration towards the atherosclerotic plaque, which have significant effects
Inflammatory genes polymorphisms and their effects on CVD
Inflammatory system and cytokines involved in it have essential roles in the development of CVD. Gene polymorphisms of these cytokines through changes in their expressions can serve as risk factors in CVD [111]. Presence of −174 G>C polymorphism in IL-6 gene increases the risk of developing MI via overexpression of IL-6 in CC genotype and elderly compared to younger individuals and GG genotype [112,113]. Other studies have also shown the upregulation of CRP in 2174C allele compared to 2174G
Evaluating the effects of dietary pattern on the risk of CVD
CVD is highly affected by lifestyle, including dietary pattern, smoking, and physical activity [136], so that diet through modulation of inflammation could have an important role in the development of cardiovascular events [137]. The effect of diet on CVD depends on pro- or anti-inflammatory power composition of the diet [138]. It has been reported that dietary patterns high in refined starches, sugar, and lipids and poor in natural antioxidants and fiber could have role in creating an
Discussion
Inflammation is one of the key contributing factors in CVD, where interactions between immune cells, vascular cells, and release of inflammatory factors appear to modulate pathogenesis of disease in this process. Previous studies have indicated that delineating the underlying mechanisms of inflammatory mediators and acute phase proteins involved in this disease should be considerably beneficial both as predictive markers and targets for advancement of appropriate therapeutic approaches in
Conclusion
Given the role of inflammation in initiation, progression, and clinical complications of CVD, in this review article, this hypothesis has been proposed that the expression rates of inflammatory mediators in CVD have prognostic value. Overall, knowledge of the prognostic value of inflammatory mediators is helpful in anticipating clinical course of this disease along with the hope of improving appropriate and timely therapeutic interventions that could substantially ameliorate problems associated
Acknowledgement
We wish to thank all our colleagues in Shafa Hospital and Allied Health Sciences School, Ahvaz Jundishapur University of Medical Sciences.
Authors' contributions
N.S. conceived the manuscript and revised it; H.H., M.Sh., M.B., N.D. wrote the manuscript and prepared the Table and figure.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Conflict of interest
The authors declare no conflict of interest.
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