Table 1.
siRNA Targets in Atherosclerosis.
| Target Name | Mechanism | Study Type | References |
|---|---|---|---|
| IMMUNE MODULATOR | |||
| Toll-like receptors 2 and 4 (TLR2 and 4) | inflammation modulation via nuclear factor- kappaB, chemokine secretion and MAPK signaling | in vitro | Ji et al., 2011; Ji et al., 2010; Geng et al., 2010; Su et al., 2011; Liu et al., 2010; Meng et al., 2013 |
| Mammalian Target of Rapamycin (mTOR) | foam cell formation, LDL receptor, chemokine and MMP-2 expression | in vitro & mouse model | Yu et al., 2011; Ma et al., 2013a; Wang et al., 2013b |
| C-C chemokine receptor type 2 CCR2 | monocyte chemotaxis | mouse model | Leuschner et al., 2011; Majmudar et al., 2013) |
| Chemokine (C-X3-C motif) Receptor 1 (CX3CR1) | inflammation (TNF-alpha) and remodeling (MMP-9), EC to dendritic cell interaction | in vitro | Butoi et al., 2011; Liu et al., 2011 |
| C-X-C chemokine receptor type 7 (CXCR7) | inflammation, chemotaxis (sdf-1) | in vitro | Ma et al., 2013b) |
| Endoplasmic Reticulum (ER) Stress Transducers (protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol-requiring protein 1 (IRE-1) | inflammation, leukocyte adhesion (ICAM-1, P-Selectin) | in vitro | Luo et al., 2013; Yao et al., 2013; Moreno et al., 2013 |
| S100 alarmin S100A9 | neutrophil activity, macrophage vesicle calcification, SMC differentiation | in vitro | New et al., 2013; Inaba et al., 2009 |
| LIPID METABOLISM | |||
| Oxidized low-density lipoprotein receptor 1 (LOX-1) | oxLDL internalization and degradation | in vitro | Wang et al., 2013a; Zhang et al., 2013b |
| Apolipoprotein B (apoB) | lipoprotein shuttling | mouse model | Tadin-Strapps et al., 2011) |
| REACTIVE OXYGEN SPECIES | |||
| NADPH oxidase 1 (Nox1), NADPH oxidase, EF-hand calcium binding domain 5 (Nox5) | leukocyte adhesion, chemokine ligand expression | in vitro | Gray et al., 2013; Bayat et al., 2012; Rius et al., 2013 |
| TRANSCRIPTION FACTORS | |||
| Nuclear factor-kappaB (NF-κB) | Il-17 induced VCAM expression in VSMC | in vitro | Zhang et al., 2013a |
| Kruppel Like Factor 4 (KLF4) | SMC differentiation (Myocd) | in vitro | Turner et al., 2013 |
| MATRIX METALLOPROTEINASES (MMPs) | |||
| Matrix metalloproteinase 2 and 9 (MMP−2/−9) | ECM remodeling, migration, apoptosis | in vitro | Johnson et al., 2011; Kim et al., 2012; Kowluru et al., 2011 |
| PROTEIN KINASES | |||
| Extracellular signal-regulated kinases 1/2 (ERK1/2) | proinflammatory cytokines, cell adhesion molecules, oxLDL uptake, proliferation | in vitro | Li et al., 2010 |
| C-Jun | IL-6 and RANKL signaling | in vitro | Zhang et al., 2012; Kim et al., 2010 |
| c-Jun NH2-terminal kinases (JNK, JNK2) | serum amyloid A signaling, EC alignment, NF-kB signaling, SMC migration and pro- liferation | in vitro | Dong et al., 2011; Wang et al., 2011; Hahn et al., 2011; Wang et al., 2011; Shyu et al., 2012 |
| p38 mitogen-activated protein kinase family (p38 MAPK) | LDL accumulation in macrophages, PPAR- gamma expression | in vitro | Mei et al., 2012 |
| Protein kinase C (PKC) - (PKCα/β/δ) | SMC adhesion, migration, CD36 expres- sion, proinflammatory cytokines (IL-1, TNF-alpha, MCP-1, IL-6), apoptosis | in vitro | Jialal & Devaraj, 2012; Jialal et al., 2013a; Jialal et al., 2013b; Karunakaran et al., 2013; Larroque-Cardoso et al., 2013 |
| Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) | cholesterol flux in macrophages | in vitro | Mo et al., 2011; Park et al., 2013b |
| CELL SURFACE MOLECULES/MEMBRANE RECEPTORS/MEMBRANE ASSOCIATED PRO TEINS | |||
| Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1 or CD31) and Fibronectin (FN) | VCAM-1 expression, NF-kB signaling | in vitro | Wang et al., 2011; Feaver et al., 2010 |
| Eph receptors Ephrin A2 (EphA2) and Ephrin A4 (EphA4) | VCAM-1 expression; monocyte adhesion, EC stress fiber formation | in vitro | Funk et al., 2012; Jellinghaus et al., 2013 |
| Caveolin (Cav-1) | cholesterol flux in macrophages, macrophage differentiation. ICAM expression, proinflammatory cytokine (IL-1beta), EC tube formation | in vitro | Hu et al., 2010; Fu et al., 2012; Jagielska et al., 2012 |