高脂血症治疗目标高密度脂蛋白
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atherosclerosis in transgenic mice and rabbits Regression of pre-existing atherosclerosis in
animals
Slide Source LipidsOnline
www.lipidsonline.org
HDL Metabolism as a Therapeutic Target: Potential Strategies Increase apo A-I production Promote reverse cholesterol transport Delay catabolism of HDL
<40 mg/dL <50 mg/dL 130/85 mm Hg 110 mg/dL
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
Smoke
Are sedentary
Are obese
Are insulin resistant or diabetic
Have hypertriglyceridemia
Have chronic inflammatory disorders
Slide Source LipidsOnline
Slide Source LipidsOnline
www.lipidsonline.org
ATP III: The Metabolic Syndrome
Diagnosis is established when 3 of these risk factors are present.
Risk Factor
Administration of peptides based on apo A-I sequence
Somatic gene transfer of apo A-I DNA (liver, intestine, muscle, hematopoetic cells)
Slide Source LipidsOnline
Slide Source LipidsOnline
www.lipidsonline.org
Approaches to Increasing Apo A-I Production
Small molecule upregulation of apo A-I gene transcription
Intravenous infusion of recombinant protein (wild-type apo A-I, apo A-IMilano)
Abdominal obesity (Waist circumference)
Men Women TG HDL-C
Men Women
Blood pressure
Fasting glucose
Βιβλιοθήκη Baidu
Defining Level
>102 cm (>40 in) >88 cm (>35 in)
150 mg/dL
www.lipidsonline.org
HDL as a Therapeutic Target: Potential Strategies Increase apo A-I production Promote reverse cholesterol transport Delay catabolism of HDL
HDL as a Therapeutic Target Daniel J. Rader, M.D.
Slide Source LipidsOnline
www.lipidsonline.org
Low HDL-C is an Independent Predictor of CHD Risk Even When LDL-C is Low
ATP III: New Definition of Low HDL-C
Low HDL-C was redefined as <40 mg/dL
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
www.lipidsonline.org
Production of Apo A-I by Liver and Intestine
Liver
Intestine
A-I A-II
HDL
A-I
HDL
Slide Source LipidsOnline
www.lipidsonline.org
Increased Apo A-I Production is Antiatherogenic in Animals Reduced initiation and progression of
3.0
Risk of CHD
2.0
1.0
0.0
100
160
220
LDL-C (mg/dL)
Gordon T et al. Am J Med 1977;62:707-714.
25
45 65
HDL-C
85
(mg/dL)
Slide Source LipidsOnline
www.lipidsonline.org
Slide Source LipidsOnline
www.lipidsonline.org
HDL and Reverse Cholesterol Transport
Bile
FC CE
SR-BI
Liver
A-I
FC
CE
Mature HDL
A-I
LCAT
FC
CE FC
Nascent ABCA1
Slide Source LipidsOnline
www.lipidsonline.org
Is HDL-C Simply a Marker of Increased Cardiovascular Risk?
Low HDL-C levels are commonly found in patients who:
animals
Slide Source LipidsOnline
www.lipidsonline.org
HDL Metabolism as a Therapeutic Target: Potential Strategies Increase apo A-I production Promote reverse cholesterol transport Delay catabolism of HDL
<40 mg/dL <50 mg/dL 130/85 mm Hg 110 mg/dL
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
Smoke
Are sedentary
Are obese
Are insulin resistant or diabetic
Have hypertriglyceridemia
Have chronic inflammatory disorders
Slide Source LipidsOnline
Slide Source LipidsOnline
www.lipidsonline.org
ATP III: The Metabolic Syndrome
Diagnosis is established when 3 of these risk factors are present.
Risk Factor
Administration of peptides based on apo A-I sequence
Somatic gene transfer of apo A-I DNA (liver, intestine, muscle, hematopoetic cells)
Slide Source LipidsOnline
Slide Source LipidsOnline
www.lipidsonline.org
Approaches to Increasing Apo A-I Production
Small molecule upregulation of apo A-I gene transcription
Intravenous infusion of recombinant protein (wild-type apo A-I, apo A-IMilano)
Abdominal obesity (Waist circumference)
Men Women TG HDL-C
Men Women
Blood pressure
Fasting glucose
Βιβλιοθήκη Baidu
Defining Level
>102 cm (>40 in) >88 cm (>35 in)
150 mg/dL
www.lipidsonline.org
HDL as a Therapeutic Target: Potential Strategies Increase apo A-I production Promote reverse cholesterol transport Delay catabolism of HDL
HDL as a Therapeutic Target Daniel J. Rader, M.D.
Slide Source LipidsOnline
www.lipidsonline.org
Low HDL-C is an Independent Predictor of CHD Risk Even When LDL-C is Low
ATP III: New Definition of Low HDL-C
Low HDL-C was redefined as <40 mg/dL
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
www.lipidsonline.org
Production of Apo A-I by Liver and Intestine
Liver
Intestine
A-I A-II
HDL
A-I
HDL
Slide Source LipidsOnline
www.lipidsonline.org
Increased Apo A-I Production is Antiatherogenic in Animals Reduced initiation and progression of
3.0
Risk of CHD
2.0
1.0
0.0
100
160
220
LDL-C (mg/dL)
Gordon T et al. Am J Med 1977;62:707-714.
25
45 65
HDL-C
85
(mg/dL)
Slide Source LipidsOnline
www.lipidsonline.org
Slide Source LipidsOnline
www.lipidsonline.org
HDL and Reverse Cholesterol Transport
Bile
FC CE
SR-BI
Liver
A-I
FC
CE
Mature HDL
A-I
LCAT
FC
CE FC
Nascent ABCA1
Slide Source LipidsOnline
www.lipidsonline.org
Is HDL-C Simply a Marker of Increased Cardiovascular Risk?
Low HDL-C levels are commonly found in patients who: