Inflammatory Markers and the Metabolic Syndrome
Insights From Therapeutic Interventions
Kwang Kon Koh, MD, PhD, FACC*,*,
Seung Hwan Han, MD* and
Michael J. Quon, MD, PhD
* Division of Cardiology, Gil Heart Center, Gachon Medical School, Incheon, Korea
Diabetes Unit, Laboratory of Clinical Investigation, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland
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Figure 1 Injury to the arterial surface activates endothelial cells and initiates synthesis of pro-inflammatory proteins including chemokines, cell adhesion molecules, and cytokines as well as growth factors and prothrombogenic substances. Monocytes attracted into the vessel wall are transformed into macrophages, which incorporate oxidized low-density lipoprotein (LDL), becoming lipid-laden foam cells. Modified from Koh KK (2).
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Figure 2 Many stimuli initiate transcription of genes in endothelium that encode protein mediators of inflammation and hemostasis. Statins and fibrates might modulate this process by inhibiting activation of nuclear transcription factor, NF-kappaB. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type I receptor blockers (ARBs) modulate this process by inhibiting binding of angiotensin II to type I receptor, which decreases activation of NF-kappaB by oxygen free radicals. Modified from Koh KK (2).
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Figure 3 Percent change in monocyte chemoattractant protein (MCP)-1 levels from respective pretreatment values after treatment with simvastatin alone, combined therapy, and losartan alone (p = 0.030 by analysis of variance [ANOVA]) (27). The SEM is identified by bars.
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Figure 4 Pro-inflammatory cytokines such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)- released from injured arteries initiate hepatic synthesis of acute phase reactants. Some acute phase reactants have effects on the arterial segment and contribute to the inflammatory response. Modified from Koh KK (2).
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Figure 5 Percent change in high-sensitivity C-reactive protein (hsCRP) levels from respective pretreatment values after treatment with simvastatin alone, combined therapy, and ramipril alone (p = 0.004 by analysis of variance [ANOVA]) (42). Median values are provided.
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Figure 6 Adiponectin, a cytokine secreted by adipose cells, plays a key role in opposing insulin resistance. Adiponectin has novel vascular actions to directly stimulate production of NO in endothelial cells using phosphatidylinositol (PI) 3-kinase-dependent pathways involving phosphorylation of endothelial nitric oxide synthase (eNOS) by adenosine-monophosphate–activated protein kinase (AMPK) (66). Others report that adiponectin reduces expression of adhesion molecules in endothelial cells and decreases cytokine production from macrophage by inhibiting nuclear transcription factor NF-kappaB signaling through cyclic adenosine monophosphate (cAMP)-dependent pathway (67,68).
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Figure 7 Percent change in adiponectin levels from respective pretreatment values after treatment with simvastatin alone, combined therapy, and losartan alone (p < 0.001 by analysis of variance [ANOVA]) (27). The SEM is identified by bars.
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