PPAR-activating compounds
Overview of compounds that activate PPARs, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.
Compound | Primary Action | ABCA1 | ABCG1 | Cholesterol Efflux | Reference | |||
---|---|---|---|---|---|---|---|---|
PPARγ-activating compounds | ||||||||
15d-PGJ2 | Prostanoid-specific receptor inhibitor | ↑ | THP-1 | ↑ | PMa | Lipid-loaded HMC | Ruan et al., 2003; Jiang and Li, 2017 | |
↑ | HMC | ↑ | apoA-I | |||||
↓↓ | PMa | PMa | ||||||
↓ | apoA-I | |||||||
↑ | HDL | |||||||
4010B-30 | Benzamide analog | ↑ | RAW264.7 | — | RAW264.7 | Du et al., 2015b | ||
↑ | HepG2 | ↑ | apoA-I | |||||
Ciglitazone | PPARγ agonist | ↑= | THP-1 | ↑ | THP-1 | ↑ | THP-1 | Argmann et al., 2003, 2005 |
E3317 | PPARγ agonist | RAW264.7 | RAW264.7 | Wang et al., 2018 | ||||
↑↑ | LO2 | ↑ | apoA-I | |||||
GQ-11 | PPARγ/α agonist | ↑ | Liverb | Silva et al., 2018 | ||||
GW1929 | PPARγ agonist | ↑↑ | HepG2 | — | — | Mogilenko et al., 2010 | ||
GW7845 | PPARγ agonist | ↑ | THP-1 | — | ↑ | THP-1 | Chawla et al., 2001; Oliver et al., 2001 | |
Propofol | GABAB receptor agonist | ↑↑ | THP-1 | ↑↑ | THP-1 | ↑ | THP-1 | Ma et al., 2015; Hsu et al., 2018 |
↑ | RAECs | RAECs | ||||||
↑ | HDL | |||||||
Lysophosphatidylcholine | Unknown | ↑↑ | PMa | — | ↑ | PMa | Hou et al., 2007 | |
Mycophenolic acid | Inosine-5′-monophosphate dehydrogenase inhibitor | ↑↑ | HepG2 | — | — | Xu et al., 2011 | ||
Pioglitazone | PPARγ agonist | ↑↑ | THP-1 | ↑↑ | THP-1 | THP-1 | Panzenboeck et al., 2006; Nakaya et al., 2007; Tanabe et al., 2008; Ogata et al., 2009; Cocks et al., 2010; Ozasa et al., 2011; Wang et al., 2014b, 2015b; Jiang and Li, 2017; Silva et al., 2018 | |
↑ | HepG2 | ↑ | Monocyte-derived macrop | ↑ | apoA-I | |||
↑↑ | pBCECs | ↑ | PMa | ↑ | HDL | |||
↑ | gBECs | ↑ | Diabetic patientsc | ↓ | pBCECs | |||
↑↑ | WI38 fibroblasts | ↑ | Rat cortical neurons | ↑ | gBECs | |||
↑ | Monocyte-derived macropc | ↑ | WI38 fibroblasts | |||||
↓↓ | PMa | PMa | ||||||
= | Liverb | ↓ | apoA-I | |||||
↑ | Diabetic patientsc | ↑ | HDL | |||||
↑ | Rat cortical neurons | ↑ | Diabetic patientsc | |||||
Rosiglitazone | PPARγ agonist | ↑↑ | THP-1 | ↑↑ | THP-1 | ↑ | THP | Chawla et al., 2001; Chinetti et al., 2001; Claudel et al., 2001; Li et al., 2004, 2015; Llaverias et al., 2006 |
↑ | RAW264.7 | ↑ | macropd | ↑ | RAW264.7 | |||
↑ | HepG2 | ↑ | Aortad | ↑ | macropd | |||
== | macropd | ↑ | PMe | |||||
↑ | PMe | ↑ | Hepatocytese | |||||
↑= | Hepatocytese | |||||||
= | Aortad | |||||||
Aorta lesione | ||||||||
Telmisartan | Angiotensin receptor 1 antagonist | ↑↑ | THP-1 | ↑↑ | THP-1 | ↑ | THP-1 | Nakaya et al., 2007 |
↑ | Monocyte-derived macropc | ↑ | Monocyte-derived macropc | |||||
Troglitazone | PPARγ agonist | ↑ | THP-1 | ↑ | PMa | ↑ | pBCECs | Cabrero et al., 2003; Panzenboeck et al., 2006; Lee et al., 2008; Jiang and Li, 2017 |
↓↑ | pBCECs | PMa | ||||||
↑↑ | gBECs | ↓ | apoA-I | |||||
= | Monocyte-derived macropc | ↑ | HDL | |||||
↓↓ | PMa | |||||||
PPARα-activating compounds | ||||||||
Aspirin | COX-1/2 inhibitor | ↑ | THP-1 | — | RAW264.7 | Viñals et al., 2005; Wang et al., 2010 | ||
↑↑ | RAW264.7 | ↑ | apoA-I | |||||
Atorvastatin | HMG-CoA reductase inhibitor | ↑ | THP-1 | ↑ | THP-1 | THP-1 | Argmann et al., 2005; Maejima et al., 2011; Nicholls et al., 2015, 2017 | |
↑ | McARH7777 | ↑ | apoA-I | |||||
↑ | HDL | |||||||
Bezafibrate | Pan-PPAR agonist | ↑↑ | THP-1 | — | ↑ | THP-1 | Cabrero et al., 2003; Ruan et al., 2003; Panzenboeck et al., 2006; Hossain et al., 2008; Inaba et al., 2008; Ogata et al., 2009 | |
↑↑ | HepG2 | ↑ | HepG2 | |||||
== | pBCECs | = | pBCECs | |||||
↑↑ | W138 fibroblast | ↑ | W138 fibroblast | |||||
↑ | HMC | Lipid-loaded HMC | ||||||
↑↑ | Primary hepatocytes | ↑ | apoA-I | |||||
= | Monocyte-derived macropc | ↑ | Primary hepatocytes | |||||
= | aortab | |||||||
Clofibrate | PPARα agonist | ↑= | HepG2 | — | — | Guan et al., 2003; Kobayashi et al., 2011 | ||
= | Primary hepatocytesf | |||||||
↑ | Liverf | |||||||
Fenofibrate | PPARα agonist | ↑↑ | THP-1 | ↑ | Liverg | ↑ | THP-1 | Forcheron et al., 2002; Lin and Bornfeldt, 2002; Cabrero et al., 2003; Thomas et al., 2003; Arakawa et al., 2005; Kooistra et al., 2006; Hossain et al., 2008; Tanabe et al., 2008; Ogata et al., 2009; Jiang and Li, 2017 |
↑↑ | RAW264.7 | ↑ | RAW264.7 | |||||
↑↑ | HepG2 | ↑ | HepG2 | |||||
=↑ | pBCECs | = | pBCECs | |||||
↑↑ | Balb/3T3 | = | Balb/3T3 | |||||
↑↑ | W138 fibroblast | ↑ | W138 fibroblast | |||||
↑↑ | Primary hepatocytes | ↑ | Primary hepatocytes | |||||
= | Monocyte-derived macropc | |||||||
↑ | PMa | |||||||
↑ | Liverh | |||||||
↑ | Diabetic patientsc | |||||||
↑ | Aortai | |||||||
Gemfibrozil | PPARα agonist | ↑↑ | THP-1 | — | ↑ | THP-1 | Hossain et al., 2008; Ogata et al., 2009 | |
↑↑ | HepG2 | ↑ | HepG2 | |||||
↑↑ | W138 fibroblast | ↑ | W138 fibroblast | |||||
↑↑ | Primary hepatocytes | ↑ | Primary hepatocytes | |||||
GW7647 | PPARα agonist | ↑ | THP-1 | = | macropd | = | THP-1 | Oliver et al., 2001; Li et al., 2004; Wang et al., 2010; Nakaya et al., 2011 |
↑↑ | RAW264.7 | = | Aortad | RAW264.7 | ||||
== | macropd | ↑↑ | BMMa | ↑ | apoA-I | |||
== | Atherosclerotic lesiond | = | macropd | |||||
↑↑ | BMMa | ↑ | BMMa | |||||
LY518674 | PPARα agonist | ↑↑ | THP-1 | — | ↑ | THP-1 | Hossain et al., 2008; Ogata et al., 2009 | |
↑↑ | HepG2 | ↑ | HepG2 | |||||
↑↑ | W138 fibroblast | ↑ | W138 fibroblast | |||||
↑↑ | Primary hepatocytes | ↑ | Primary hepatocytes | |||||
Pitavastatin | HMG-CoA reductase inhibitor | ↓ | J774 | — | ↓ | J774 | Zanotti et al., 2004, 2006; Kobayashi et al., 2011; Maejima et al., 2011 | |
↑ | HepG2 | ↑ | Fu5AH | |||||
↑↑ | McARH7777 | ↓ | PMa,b,d | |||||
↑ | Liverf | = | LXR−/− mice | |||||
Pravastatin | HMG-CoA reductase inhibitor | ↑↑ | 3T3-L1 | ↓↓ | 3T3-L1 | ↓ | 3T3-L1 | Maejima et al., 2011; Mostafa et al., 2016 |
= | McARH7777 | |||||||
Rosuvastatin | HMG-CoA reductase inhibitor | = | Hepatocytesa | ↑ | J774 | Shimizu et al., 2014; Mostafa et al., 2016 | ||
↑ | BMMa | |||||||
↑ | RCTa | |||||||
Simvastatin | HMG-CoA reductase inhibitor | ↑ | McARH7777 | == | PMi | THP-1 | Argmann et al., 2005; Guan et al., 2008; Maejima et al., 2011; Song et al., 2011; Ying et al., 2013; Gong et al., 2014 | |
↑ | Diabetic patients with hyperlipidemia | == | Liveri | ↑ | apoA-I | |||
== | PMd | = | HDL | |||||
↑↑ | Liveri | ↑ | RAW264.7 | |||||
WY14643 | PPARα agonist | ↑↑ | THP-1 | ↑ | THP-1 | ↑ | THP-1 | Chinetti et al., 2001; Ruan et al., 2003; Beyer et al., 2004; Arakawa et al., 2005; Lee et al., 2008; Maejima et al., 2011 |
↑↑ | RAW264.7 | ↑ | RAW264.7 | |||||
↑↑ | gBECs | = | Balb/3T3 | |||||
↑↑ | Balb/3T3 | Lipid-loaded HMC | ||||||
= | McARH7777 | ↑ | apoA-I | |||||
↑ | Livera | |||||||
Wy,14,563 | PPARα agonist | — | — | ↑ | THP-1 | Chawla et al., 2001 | ||
PPARδ/β-activating compounds | ||||||||
Carbaprostacyclin (cPGI) | PPARδ agonist | — | — | ↑ | THP-1 | Chawla et al., 2001 | ||
GW0742 | PPARδ agonist | = | Livera | = | Livera | ↑ | BMMa | Li et al., 2004; Briand et al., 2009 |
= | Small intestinea | = | Small intestinea | = | macropa | |||
== | macropd | = | macropd | |||||
= | Atherosclerotic lesiond | = | Aortad | |||||
GW501515 | PPARδ agonist | ↑↑ | THP-1 | = | HSKM | ↑ | THP-1 | Oliver et al., 2001; Sprecher et al., 2007; Ogata et al., 2009 |
↑↑ | W138 fibroblast | ↑ | W138 fibroblast | |||||
↑ | 1BR3N fibroblast | ↑ | 1BR3N fibroblast | |||||
↑ | Intestinal FHS74 | ↑ | Intestinal | |||||
↑ | HSKM | HSKM |
BMM, bone marrow– derived macrophage; gBECS, gallbladder epithelial cells; HMC, human mast cell; HSKM, human skeletal muscle cell; macrop, macrophage; pBCECs, porcine brain capillary endothelial cells; PM, peritoneal macrophages; RAECs, rat aortic endothelial cells.
↵a C75BL/6 mice.
↵b LDLR−/− C75BL/6 mice.
↵c Human.
↵d LDLR−/− C75BL/6 hypercholesterolemic mice.
↵e New Zealand White rabbits.
↵f Male Wistar rats.
↵g Male Zucker diabetic fatty rats.
↵h 129SV mice.
↵i Female E3L transgenic mice.