Cytochrome P450 — physiological key factor against cholesterol accumulation and the atherosclerotic vascular process

Figures & data

Table I. Cytochrome P450 enzymes in the synthesis and metabolism of major oxysterols, bile acids and cholesterol.

CYP7A1	cholesterol hydroxylase: 7α‐hydroxycholesterol synthesis
CYP8B1	12α‐hydroxylase of 7α‐hydroxycholesterol: bile acid synthesis
CYP27A1	cholesterol hydroxylase: 27‐hydroxycholesterol synthesis
CYP7B1	7α‐hydroxylase of 27‐hydroxycholesterol: bile acid synthesis
CYP46A1	cholesterol hydroxylase: 24S‐hydroxycholesterol synthesis
CYP39A1	7α‐hydroxylase of 24S‐hydroxycholesterol: bile acid synthesis
CYP3A4	cholesterol hydroxylase: 4β‐hydroxycholesterol synthesis, bile acid synthesis, detoxification of bile acids
CYP51A1	lanosterol 14α‐demethylase: cholesterol synthesis

Table II. Effects of P450‐inducing and ‐inhibiting compounds on plasma HDL cholesterol (HDL‐C) and apo AI levels, apo AI synthesis (‐S), ABCA1 and/or ABCG1 activity (‐A), development of atherosclerosis^a and morbidity/mortality ^b.

	HDL‐C	Apo AI	Apo AI‐S	ABCA1/ABCG1‐A	Atherosclerosis	Morbidity/mortality
P450‐inducers:
Fibrate	↑	↑	↑	↑	↓	↓
Statin	↑	↑	↑	↑	↓	↓
Cholestyramine	↑	↑	↑		↓	↓
TZD	↑	↑	↑	↑	↓	↓
Anticonvulsant	↑	↑	↑		↓
Alcohol	↑	↑	↑	↑	↓	↓
P450 inhibitors:
Carbon monoxide	↓^c	↓^c			↑	↑
Ketoconazole	↓	↓	↓	↓
Interferon‐γ	↓	↓	↓	↓	↑	↑

^a Biochemical or histological study: promotion 109,113,115; inhibition 125,126. Clinical angiographic or ultrasonographic study: retardation of progression or prevention/regression by P450 inducers 118–124,127,128.

^b Morbidity and/or mortality from CHD and/or other cardiovascular disease, and/or all‐cause mortality 112,130–138.

^c Decrease with exposure to CO 110 or environmental tobacco smoke 111.

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