Table 3.
Mechanisms mediating PM-induced proatherogenic effects. In vitro and experimental animal evidence
| Mechanisms | Indicators | References |
|---|---|---|
| Evidence in cellular and/or animal studies | ||
| Oxidative stress in systemic tissues | Increased liver peroxidation and upregulation of antioxidant genes in liver | (Gong et al. 2007; Araujo et al. 2008) |
| Alteration of circulating lipoproteins | Oxidative modification of LDL | (Soares et al. 2009) |
| Generation of dysfunctional HDL | (Araujo et al. 2008) | |
| Vascular prooxidant effects | Increased ROS production in ECs and macrophages | (Goldsmith et al. 1998; Hiura et al. 1999; Soukup et al. 2000; Bai et al. 2001; Lee and Kang 2002; Hirano et al. 2003; Li et al. 2004; Li et al. 2006; Chio et al. 2007; Li et al. 2010; Montiel-Davalos et al. 2010) |
| Upregulation of antioxidant genes in ECs and macrophages | (Hirano et al. 2003; Li et al. 2004; Gong et al. 2007; Li et al. 2010) | |
| Activation of NADPH oxidase in ECs and macrophages | (Beck-Speier et al. 2005; Li et al. 2006; Mo et al. 2009) | |
| Induction of electron leaks in mitochondrial electron transport complexes in ECs | (Li et al. 2006) | |
| Increased ROS in vessels with atherosclerotic plaques | (Sun et al. 2005; Ying et al. 2009a) | |
| Vascular proinflammatory effects | Greater proinflammatory cytokine production in ECs and macrophages | (Alfaro-Moreno et al. 2002; Fujii et al. 2002; Jimenez et al. 2002; Amakawa et al. 2003; Osornio-Vargas et al. 2003; Pozzi et al. 2003; Brown et al. 2004; Becker et al. 2005a; Ishii et al. 2005; Imrich et al. 2007; Li et al. 2010) |
| Increased expression of cell adhesion molecules in ECs | (Li et al. 2010) | |
| Greater monocyte adhesion to ECs | (Li et al. 2010) | |
| Monocyte migration and recruitment in atherosclerotic vessels | (Yatera et al. 2008) | |
| Activation of NF-kB in ECs and macrophages | (Mondal et al. 2000; Montiel-Davalos et al. 2010) | |
| Activation of MAPK in ECs and macropages | (Hiura et al. 1999; Sumanasekera et al. 2007; Mo et al. 2009) | |
| Activation of ERK1/2 pathways in ECs and macrophages | (Beck-Speier et al. 2005; Mo et al. 2009) | |
| Increased proinflammatory cytokines in circulating blood | (Mutlu et al. 2007; Tamagawa et al. 2008) | |
| Vascular toxic effects | Decrease in viability of ECs and macrophages | (Hiura et al. 1999; Bai et al. 2001; Lee and Kang 2002) |
| Increased in ECs and macrophages | (Hiura et al. 1999; Lee and Kang 2002; Montiel-Davalos et al. 2010) | |
| Increase in EC permeability and/or upregulation of genes involved in EC permeability | (Nadadur et al. 2009; Wang et al. 2010) | |
| Antiproliferative effects in ECs | (Yamawaki and Iwai 2006) | |
| Evidence in humans | Subclinical measures | |
| Systemic inflammation | Elevated circulating pro-inflammatory biomarkers/mediators (figrinogen, CRP, TNF-α, IL 1-ß, IL-6, IL-7, GM-CSF, ICAM-1) | (Ibald-Mulli et al. 2001; van Eeden et al. 2001; Pope et al. 2004; Riediker et al. 2004; Analitis et al. 2006; Peters et al. 2006; Zeka et al. 2006; Chuang et al. 2007; O’Neill et al. 2007; Ruckerl et al. 2007) |
| Systemic oxidative stress | Increased biomarkers of lipid, protein or DNA oxidation | (Sorensen et al. 2003; Vinzents et al. 2005; Brauner et al. 2007) |
| Elevated plasma homocysteine | (Baccarelli et al. 2007; Park et al. 2008) | |
| Inhibition of oxidative response by w-3 PUFA | (Romieu et al. 2008) | |
| Systemic hypertension | Elevated systemic diastolic and/or systolic blood pressure | (Ibald-Mulli et al. 2001; Lippmann et al. 2003; Choi et al. 2007; Chuang et al. 2007; Diez Roux et al. 2008; Dvonch et al. 2009; Zanobetti and Schwartz 2009) |
| Elevated endothelin-1 levels | (Peters et al. 2006) | |
CRP C-reactive protein, ECs endothelial cells, ET-1 endothelin 1, GM-CSF granulocyte macrophage colony-stimulating factor, ICAM-1 intercellular adhesion molecular 1; IL interleulin, PUFA polyunsaturated fatty acids, ROS reactive oxygen species, TNF-α tumor necrosis factor α