Nutrition & Metabolism

Table 1 Quick reference guide: Overview of available reverse cholesterol transport studies

From: Regulation of reverse cholesterol transport - a comprehensive appraisal of available animal studies

Factor investigated	Intervention	Animal model	Type of macrophages used	Effect on RCT	Ref
Macrophage
ApoE	ApoE knockout macrophages	Wild-type mice	Peritoneal	↓	[24]
CE hydrolysis	Human nCEH transgenic macrophages	LDLr knockout mice	Peritoneal	↑	[29]
ABCA1	ABCA1 knockout macrophages	Wild-type mice	Bone marrow	↓	[30, 31]
ABCG1	ABCG1 overexpression in macrophages	Wild-type mice	J774	↑	[31]
	ABCG1 knockdown in macrophages	Wild-type mice	J774	↓	[31]
	ABCG1 knockout macrophages	Wild-type mice	Bone marrow	↓	[31]
ABCA1/ABCG1	ABCA1/ABCG1 double knockdown in macrophages	Wild-type mice	J774	↓	[31]
	ABCA1/ABCG1 double knockout macrophages	Wild-type mice	Bone marrow	↓	[32]
SR-BI	SR-BI knockout macrophages	Wild-type mice	Bone marrow	=	[31]
	SR-BI knockout macrophages	Wild-type mice	Bone marrow	=	[33]
ABCA1/SR-BI	ABCA1/SR-BI double knockout macrophages	Wild-type mice	Bone marrow	↓	[33]
PLTP	PLTP knockout macrophages	Wild-type mice	Peritoneal	=	[34]
CETP	CETP overexpression in macrophages	Wild-type mice	RAW 267.4	=	[35]
	CETP overexpression in macrophages	Wild-type mice	Peritoneal	=	[36]
15(S)-lipoxygenase-1	Human 15(S)-lipoxygenase-1 overexpression in macrophages	Wild-type mice	RAW 267.4	↑	[37]
Myeloid differentiation primary response protein 88	MyD88 knockout macrophages	Wild-type	Peritoneal	↓	[38]
Transport through the plasma compartment
ApoA-I	Adenoviral overexpression human apoA-I	Wild-type mice	J774	↑	[18]
	ApoA-I knockout	LDLr/apobec double knockout mice	J774	↓	[39]
	Adenoviral overexpression mouse or human apoA-I (wild-type or apoA-I Milano)	ApoA-I knockout mice	J774	↑	[40, 41]
	Ro 11-1464	Human apoA-I transgenic mice	J774	↑	[42]
ApoA-I tertiary structural domain	AAV overexpression domain-swap variants of human and mouse apoA-I	ApoA-I knockout mice	J774	↑	[40]
ApoA-I Milano versus wild-type apoA-I	AAV overexpression	ApoA-I knockout mice	J774	=	[41]
ApoA-I mimetic peptides	D-4 F	ApoE knockout mice	J774	↑	[43]
	5A	Wild-type mice	RAW 264.7	↑	[17]
	ATI-5261	ApoE knockout mice	J774	↑	[44]
HDL particle formation	ABCA1 knockout	ABCA1 knockout mice	Endogenous	↓	[45]
	ABCA1 knockout	ABCA1 knockout mice	Peritoneal	↓	[33]
	Probucol	Wild-type mice	J774	=	[46]
	Probucol	SR-BI knockout mice	J774	↑	[46]
LCAT	AAV overexpression human LCAT	Human apoA-I transgenic mice	J774	↓	[47]
	AAV overexpression human LCAT	Human apoA-I transgenic mice overexpressing SR-BI	J774	=	[47]
	AAV overexpression human LCAT	Human apoA-I transgenic mice overexpressing human CETP	J774	=	[47]
	LCAT knockout	LCAT knockout mice	J774	↓	[47]
Hepatic lipase	HL knockout	HL knockout mice	J774	=	[48]
Endothelial lipase	EL knockout	EL knockout mice	J774	=	[48]
	Inhibition hepatic proprotein convertases	Wild-type mice	J774	↓	[49]
Hepatic lipase/endothelial lipase	HL/EL double knockout	HL/EL double knockout mice	J774	=	[48]
PLTP	PLTP overexpression	Human PLTP transgenic mice	Peritoneal	↓	[34]
CETP	Adenoviral CETP overexpression	Wild-type mice	RAW 264.7	↑	[35]
	AAV overexpression human CETP	Apobec knockout mice	J774	↑	[50]
	AAV overexpression human CETP	LDLr/apobec double knockout mice	J774	=	[50]
	AAV overexpression human CETP	SR-BI knockout mice	J774	↑	[50]
	CETP overexpression	Cynomolgus monkey CETP transgenic mice	P388D1 or peritoneal	=	[36]
	CETP overexpression	Human CETP transgenic mice	Bone marrow	=	[51]
CETP inhibition	Torcetrapib	Hamsters	J774	↑	[35]
	Torcetrapib	Hamsters	Peritoneal	↑	[52]
	Torcetrapib	Human CETP/human apoB100 transgenic mice	J774	↑	[53]
	Anacetrapib	Hamsters	Peritoneal	=	[52]
	Anacetrapib	Hamsters	J774	↑	[54]
	Dalcetrapib	Hamsters	Peritoneal	↑	[52]
ApoA-II	Overexpression human apoA-II	Human apoA-II transgenic mice	P388D1	↑ or =	[55]
ApoF	AAV overexpression mouse apoF	Wild-type mice	J774	=	[56]
Uptake by the liver
Selective uptake	Adenoviral overexpression SR-BI	Wild-type mice	J774	↑	[57]
	Adenoviral overexpression SR-BI	Human apoA-I transgenic mice	J774	↑	[57]
	SR-BI knockout	SR-BI knockout mice	J774	↓	[57]
	SR-BI knockout	SR-BI knockout mice	Peritoneal	↓	[33]
	SR-BI knockout	SR-BI knockout mice	Bone marrow	↓	[51]
	Transgenic CETP overexpression	SR-BI knockout mice	Bone marrow	=	[51]
	Liver-specific SR-BI knockout	SR-BI conditional knockout mice	Bone marrow	↓	[51]
	Transgenic CETP overexpression	SR-BI conditional knockout mice	Bone marrow	=	[51]
Holoparticle uptake	P2Y₁₃ knockout	P2Y₁₃ knockout mice	Peritoneal	↓	[58]
Type 1 diabetes mellitus	Alloxan	Wild-type mice	Peritoneal	↓	[59]
	Streptozotocin	Wild-type mice	J774	↓	[60]
	Streptozotocin	Hp2-2 mice	J774	↓	[60]
Excretion into the intestine
CE hydrolysis liver	Adenoviral overexpression human nCEH	Wild-type mice	J774	↑	[61]
	Carboxyl ester lipase knockout	Carboxyl ester lipase knockout mice	J774	↑	[62]
ABCG5/ABCG8	ABCG5/ABCG8 double knockout	ABCG5/ABCG8 double knockout mice	P388D1	=	[63]
Biliary sterol secretion	Bile duct ligation	Wild-type mice	Peritoneal	↓	[64]
	Surgical biliary diversion	Wild-type mice	J774	=	[65]
	Transgenic overexpression NPC1L1 in the liver	Liver-specific human NPC1L1 transgenic mice	J774	=	[65]
MDR2	MDR2 knockout	MDR2 knockout mice	Peritoneal	↓	[64]
Excretion from the body
NPC1L1 intestine	Ezetimibe	Wild-type mice	J774	↑	[66]
	Ezetimibe	Wild-type mice	RAW 264.7	↑	[67]
Cholesterol absorption intestine	Congenic 14DKK interval	14DKK congenic mice	RAW 264.7	↑	[67]
	Congenic 14DKK interval	14DKK apoE knockout congenic mice	Bone marrow	↑	[68]
Inflammation
Acute inflammatory response	LPS	Wild-type mice	Peritoneal	↓	[69]
	LPS	Wild-type mice	J774	↓	[70]
	Zymosan	Wild-type mice	RAW 264.7	↓	[71]
Human group IIA secretory phospholipase A₂	Overexpression human group IIA secretory phospholipase A₂	Human group IIA secretory phospholipase A₂ transgenic mice	Peritoneal	=	[69]
Serum amyloid A	Adenoviral overexpression human serum amyloid A	Wild-type mice	Peritoneal	=	[69]
	Adenoviral overexpression mouse serum amyloid A	Wild-type mice	Peritoneal	↓	[69]
Myeloperoxidase	Human myeloperoxidase	Wild-type mice	Peritoneal	↓	[69]
Mast cell activation	Mast cell degranulating compound 48/80	Wild-type mice treated with human apoA-I	J774	↓	[72]
Drugs
LXR agonist	GW3965	Wild-type mice	J774	↑	[73, 74]
	GW3965	LDLr/apobec double knockout mice	J774	↑	[73]
	GW3965	ApoB/CETP double transgenic mice	J774	↑	[73]
	T0901317	Wild-type BALB/c mice	J774	↑	[75]
	GW3965	Hamsters	J774	↑	[76]
	T0901317	Wild-type mice	P388D1	↑	[63]
	T0901317	ABCG5/ABCG8 double knockout mice	P388D1	=	[63]
	T0901317	Wild-type FVB mice	Peritoneal	↑	[64]
	T0901317	MDR2 knockout mice	Peritoneal	=	[64]
	GW3965	LXR double knockout mice	J774	=	[74]
	GW3965	Wild-type mice	Bone marrow (wild-type and LXR double knockout)	=	[74]
Intestine-specific LXR activation	Constitutively activated LXRα in the intestine	iVP16LXRα transgenic mice	J774	↑	[77]
Liver-specific LXR activation	Adenoviral overexpression constitutively active LXRα	Wild-type FVB mice	J774	=	[77]
Intestine-specific LXR agonist	GW6340	Wild-type mice	J774	↑	[74]
PPARα agonist	GW7647	Wild-type mice	J774	↑	[78]
	GW7647	Human apoA-I transgenic mice	J774	↑	[78]
	GW7647	LDLr/apobec double knockout mice	J774	↑	[78]
	GW7647	Human apoA-I transgenic mice	Bone marrow (PPARα knockout)	=	[78]
	GW7647	Human apoA-I transgenic mice	Bone marrow (LXR double knockout)	=	[78]
	Fenofibrate	Human apoA-I transgenic mice	P388D1	↑	[79]
	Gemfibrozil	Human apoA-I transgenic mice	P388D1	=	[79]
PPARδ agonist	GW0742	Wild-type mice	J774	↑	[66]
PPARγ agonist	GW7845	Wild-type mice	J774	↓	[80]
FXR agonist	GW4064	Wild-type mice	J774	↑	[81]
	GW4064	SR-BI knockout mice	J774	↑	[81]
Liver-specific FXR activation	Adenoviral overexpression constitutively active FXR	Wild-type mice	J774	↑	[81]
miR-33 antagonism	Anti-miR33 oligonucleotide	LDLr knockout mice	Bone marrow	↑	[82]
Liver-selective thyromimetic	T-0681	Wild-type mice	J774	↑	[83]
	T-0681	CETP transgenic mice	J774	=	[83]
Sylfonylurea agent	Glibenclamide	Wild-type mice	RAW 264.7	=	[84]
	Glimepiride	Wild-type mice	RAW 264.7	=	[84]
Anti-HIV drug	Nevirapine	Human apoA-I transgenic mice	J774	=	[85]
	Efavirenz	Human apoA-I transgenic mice	J774	↑	[85]
Phosphodiesterase 3 inhibition	Cilostazol	Wild-type mice	RAW 264.7	↑	[86]
Proteasomal inhibition	Bortezomib	Wild-type mice	RAW 264.7	↑	[87]
Propolis extract	Ethanolic extract of propolis	Wild-type mice	RAW 264.7	↑	[88]
Dietary modifications
Dietary cholesterol	Cholesterol-enriched diet	Hamsters	Peritoneal	↓	[89]
Dietary cholesterol and fat	Saturated fatty acid- and cholesterol-enriched diet	Wild-type mice	P388D1	↑	[90]
	Saturated fatty acid-enriched diet	Wild-type mice	P388D1	=	[90]
Coffee	Coffee	Wild-type mice	RAW 264.7	=	[91]
	Ferulic acid	Wild-type mice	RAW 264.7	↑	[91]
Fish oil	Fish oil	Wild-type mice	J774	↑	[92]
Exercise
Exercise	Voluntary wheel running	Wild-type mice	Peritoneal	=	[93]
	Monitored wheel running	Human CETP transgenic mice	J774	↑	[94]

Wild-type; if not otherwise stated this term refers to the use of C57BL/6 mice

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