肠道胆固醇吸收的心血管病风险[可修改版ppt]

胆固醇通过高密度脂蛋白胆固醇和 CETP从动脉壁和 周边组织清除LDL-C和乳糜微粒
Intestine
Liver
Cholesterol Pool
Remnant receptors
SR-BI
LDLR
Peripheral Tissues
CMR
CE
CETP TG
HDL
CE
CETP TG
LDL/VLDL
Nascent HDL
肠道在胆固醇体内平衡中的作用
肝脏向肠道分泌游离胆固醇和胆汁酸
Intestine
Cholesterol Pool (Micelles)
75% Biliary chol
Bile Acids
Free Chol
Cholesterol Pool
Liver
Peripheral Tissues
Blood
Atheroma
肠道胆固醇吸收的 心血管病风险
胆ቤተ መጻሕፍቲ ባይዱ醇代谢（肝脏和肠道）
肝脏与肠道是胆固醇平衡最主要的两个器官
胆固醇体内平衡是由一系列因素决定的: • 胆固醇合成 • 食物摄入 • 胆固醇吸收 • 胆固醇排泄
Dietschy JM et al. J Lipid Res. 1993;34:1637.
肝脏在胆固醇体内平衡中的作用
LCAT
Blood
Free Cholesterol
Atheroma
Barter et al. Biochim Biophys Acta. 1982;713:136.; Lewis, Rader. Circ Res. 2005;96:1221.; NCEP ATP III. Circulation. 2002;106:3143.; Rader. J Clin Invest. 2006;116(12):3090.; Singh et al. J Amer Med Assoc. 2007;298(7):786.
Liver
Cholesterol Pool
Peripheral Tissues
LDLR
Hepatic Apo B100
VLDL
lDL
LDL
Blood
Atheroma
Kesanami et al. J Clin Invest. 1983;71:950.; Goldstein JL, Brown MS. J Biol Chem. 1974;249(16):5153.; Brown MS, Goldstein JL. Proc Natl Acad Sci. 1974;71:788.; Goldstein JL, Brown MS. Science. 2001;292:1310.; Rudling et al. Proc Natl Acad Sci. 1990;87:3469.
Absorption
Remnant receptors
CMR CM
Intestinal Apo B48
TG
Lipoprotein Lipase
TG
Blood
Atheroma
Rohlman et al. J Clin Invest. 1998;101:689.; Yu, Cooper. Front Biosci. 2001;6:332.; Shepherd. Eur Heart J. 2001;3:E2.
Atheroma
Blood
Apo B100 Lipoproteins 向循环系统中 运输甘油三酯，胆固醇，胆固醇
Intestine
Liver
Cholesterol Pool
Peripheral Tissues
Hepatic Apo B100
VLDL TG
lDL
TG
Lipoprotein
Lipase
O
O
Activated isoprene
Cholesterol
2
Squalene
Blood
Peripheral Tissues
Atheroma
Shepherd J. Eur Heart J Suppl. 2001;3:E2.; Buhaescu I, Izzedine H. Clin Biochem. 2007;40(9-10):575.
Intestine
LDL-C 占循环中胆固醇的2/3, LDL-C可以穿透动脉内皮
Liver
Cholesterol Pool
Peripheral Tissues
Hepatic Apo B100
VLDL
lDL
LDL
Blood
Atheroma
NCEP ATP III. Circulation. 2002;106:3143.; Brown et al. J Lipid Res. 2004;45:1155.; Rudling et al. Proc Natl Acad Sci.
肝脏向循环系统中分泌 Apo B100 Lipoproteins (VLDL)
Intestine
Liver
Cholesterol Pool
Peripheral Tissues
Hepatic Apo B100
VLDL
VLDL = very low-density lipoprotein. Goldstein JL, Brown MS. Science. 2001;292:1310.
胆固醇在肝脏内合成
Intestine
Acetyl CoA
Synthesis
Cholesterol Pool
3 CH3 COO Acetate
Liver
CH3 HO
OOC CH2 C CH2 CH2 OH
OH
Mevalonate
CH3
O
O
CH2 C CH2 CH2 O P O P O
Isoprene
Hui, Howles. Sem Cell Develop Biol. 2005;16:183.; Shepherd. Eur Heart J. 2001;3(suppl E):E2.; Turley, Dietschy. Prev Cardiol. 2003;6(1):29.
LDL
Blood
Atheroma
Goldstein JL, Brown MS. Science. 2001;292:1310.; Shepherd J. Eur Heart J Suppl. 2001;3:E2.
肝脏可以通过LDL 受体清除 Apo B100 Lipoproteins
Intestine
1990;87:3469.; Simionescu et al. Ann NY Acad Sci. 1990;598:1.; Yu, Cooper. Front Biosci. 2001;6:d332.
肝脏可以清除乳糜微滴残留物
Intestine
Liver
Cholesterol Pool
Peripheral Tissues