文档介绍：Plasma Cholesterol and Coronary
Heart Disease (CHD)
CHD Deaths
Per 1000 patients per 10 yr
Serum Cholesterol Level (mg/dl)
MRFIT:
Multiple Risk Factor Intervention Trial
Shanghai
From Dr. John M. Dietschy
(USA)
Mean LDL-Cholesterol
AGE (YEARS)
Lifetime Exposure to LDL-Cholesterol American vs. Chinese Men
Lifetime LDL Exposure Index
SMOKING
HTN
DIABETES
CHR. 9
etc.
FEMALE
From Dr. Helen H. Hobbs
Elbow Tuberous Xanthoma (15Ys Chinese Girl, FH?)
From Dr. Luya Wang in Beijing
Fluid-Mosaic Model of Cell Membrane: Cholesterol is a structural component of mammalian cell membranes
“Cholesterol Is Good”
Net Cholesterol Balance in Humans
~ 700 mg
~ 375 mg
Hepatic and
Extrahepatic
Synthesis
Total Body Cholesterol
~750 mg
Dietary+Biliary
Cholesterol
~ 400 mg
Bile FC
~ 375 mg
Feces
~ 300 mg
Bile acids
Von Bergmann K, …Grundy SM, Gastroenterology 1979:77:1183
~50%
~ 50 mg
Steroids
~ 100 mg
Skin slough
Intestinal absorption:~50%
~ 100 mg
Intestine slough
Molecular Mechanisms of Cholesterol Transport in Liver and Intestine
PCSK9, ARH
ABC transporters
ApoB
ApoB
Monogenic Hypercholesterolemia
Autosomal Familial LDLR
Familial Defective APOB
ApoB-100
Inheritance Disease Gene Defect
Dominant Hypercholesterolemia
Autosomal Autosomal Recessive ARH
Hypercholesterolemia

Sitosterolemia ABCG5/G8
Recessive
Autosomal Dominant
Hypercholesterolemia
PSCK9
Targets of Cholesterol Lowering Drugs
Inhibit cholesterol synthesis: HMG-CoA reductase inhibitors statins
Inhibit cholesterol absorption: Ezetimibe, bile acid resins, plant sterols
Reduce lipoprotein-cholesterol production: ApoB antisense oligos (ISIS)
Raise LDLR: statins, PCSK9 inhibition (drugs and antisense oligos)
Targets of Cholesterol