A review of biomarkers in cardiovascular diseases.

Report
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Biomarkers in
Cardiovascular System
Dr. Bibi Kulsoom
http://www.123rf.com/photo_9342517_cartoon-doctor-in-white-coat-attending-a-patient.html
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Cardiovascular
Cardio
Blood
Substances that
•
Lead to
•
Involved in process of
•
Released as a result of
cardiovascular disease
Vascular
http://www.highlands.edu/academics/divisions/scipe/biology/labs/cartersville/2122/diagrams/heartdiagram3.jpg
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• Appearance
of abnormal
Detected
substances
and/OR
• ed level of
normal
substances
Sampling
or
measured
in blood
as a
marker
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Cardiovascular Biomarkers:
Serum Lipid
Lipid profile: Normal Levels
– LDL : < 100mg/dl
TG
VLDL
– HDL: 40-60mg/dl
– Total chol : <200mg/dl
LDL
LDL
– Triglycerides: < 150 mg/dl
Lipid profile: Abnormal
HDL
– LDL
– HDL
– Total cholesterol
– Triacylglycerol
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Chol
HDL
Increased
risk of
CVS
Disease
HDL
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ProteinKULSOOM
Biomarkers
• Enzymes
– Creatine Kinase
•
Other Proteins
– Apolipoprotein A
– Apolipoprotein B
– Lactate Dehydrogenase
– Troponin I
– Aspartate Transaminase (AST)
– Troponin T
– Myoglobin
– Homocysteine (amino acid)
– C-reactive Protein
– Fibrinogen
– Amyloid A
– Brain Natriuretic Factor
– Atrial Natriuretic Factor
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Creatine (Phospho)
Kinase (CK, CPK)
• Tissue location & Isoenzymes : Three isoenzymes found
o CK-MM (97%): found in skeletal muscles
o CK-MB(2%): found in cardiac muscles
o CK-BB(traces): found in brain cells
 Function:
ATP
Creatine
ADP
Creatine
kinase
Creatine phosphate
• Creatine phosphate quickly regenerates ATP in the tissues.
• Arginine + Glycine + Methionine  Creatine.
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Creatine (Phospho)
Kinase (CK, CPK)
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• Main conditions with raised levels of CK-MB is heart tissue damage(e.g.
myocardial infarction (MI)).
• A total CK level will reflect the presence of tissue damage but, specific
isoenzyme (CK-MB) can identify the underlying cause or its location.
• Normal levels of total CK =30 to 180 U/L (units per liter).
• CK-MB fraction: 0-5% of CK,
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CK-MB activity: 0-15%
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Lactate Dehydrogenase
• Tissue location & Isoenzyme: five isoezymes mainly distributed
as follows:
– LDH-1: heart muscle and red blood cells.
– LDH-2: white blood cells.
– LDH-3: lungs.
– LDH-4: kidney, placenta, and pancreas.
– LDH-5 : liver and skeletal muscle.
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Lactate Dehydrogenase
 Function:
NAD+
Lactate
NADH
Lactate
dehydrogenase
Pyruvate
• Main conditions with abnormal levels: tissue damage (e.g. MI),
cancers, kidney disease, and liver disease. LDH1 is raised in heart
tissue damage.
• Normal levels: 0-280 U/L
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Lactate Dehydrogenase
• A total LDH level will reflect the presence of tissue damage but, by
itself, it cannot be used to identify the underlying cause or its
location.
• LDH too has been superseded by the newer markers and should not
be included in the ‘cardiac profile’. But LDH might be used as a marker
of cardiac dysfunction where a troponin assay is not available.
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Aspartate Transaminase
(AST)
• One of the oldest markers of MI.
• AST (+ CK and LDH) is still in use.
• Levels can be elevated in liver diseases as well.
• Little value as a marker of cardiac dysfunction and has been
superseded by newer markers.
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Cardiovascular Biomarkers:
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Serum Apolipoproteins
 Apolipoprotein A
TG
VLDL
 Apolipoprotein B
LDL
LDL
  Apolipoprotein A
  Apolipoprotein B
HDL
Chol
HDL
Increased risk of
cardiovascular Disease
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HDL
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Troponins
Troponin
Actin
http://jolisfukyu.tokai-sc.jaea.go.jp/fukyu/tayu/ACT04E/04/0406.htm
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Tropomyosin
I C T
http://img.tfd.com/mk/S/X2604-S-10.png
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Troponins
• Tissue location & types: cytoplasm of the muscle cells
• Three types, which regulate muscle contraction.
– Troponin C (TnC) binds to calcium ions to produce a conformational
change in TnI
– Troponin I (TnI) binds to actin in thin myofilaments to hold the
troponin-tropomyosin complex in place.
– Troponin T (TnT) binds to the tropomyosin strand forming a complex.
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Troponin
• TnT & TnI are specific (different) for skeletal & heart muscle.
They are measured in the blood to differentiate between
unstable angina and myocardial infarction (heart attack) in
patients with chest pain
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Myoglobin
• A protein which stores oxygen inside muscle tissue
(cardiac, skeletal & smooth).
• is the earliest biological marker of myocardial necrosis.
• This is now replaced by troponin, the more specific one.
• has the advantage of responding very rapidly, rising and falling earlier than CKMB or troponin.
• Raised in muscle damage (e.g. MI, skeletal muscle damage).
• Normal levels in blood: < 80 ng/mL.
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http://www.nap.edu/books/0309064066/xhtml/images/img00013.jpg
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Biomarkers ReleasedKULSOOM
in Blood after Myocardial
Infarction
Myoglobin
Total CK
LDH
CK-MB
Troponin I
http://1.bp.blogspot.com/-ORQRvT9GZGM/Th7e0di7WhI/AAAAAAAAoKw/Ex7Cv5eba30/s1600/CardiacEnzymes.jpg
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Biomarkers ReleasedKULSOOM
in Blood after Myocardial
Infarction
Troponin T
Troponin I
Myoglobin
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CK-MB &
Total CK
http://www.revespcardiol.org/sites/default/files/elsevier/images/255/255v56n07/grande/255v56n07-13049677tab04.gif
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Biomarkers ReleasedKULSOOM
in Blood after Myocardial
Infarction
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http://www.vetmed.vt.edu/education/Curriculum/VM8304/vet%20pathology/CASES/ISCHEMIA%202006/CARDIAC%20ENZYMES.jpg
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Biomarkers ReleasedKULSOOM
in Blood after Myocardial
Infarction
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MARKER
DETECTION
PEAK
DISAPPEARANCE
Myoglobin
1–4h
6 – 7h
24h
CK-MB mass
3 – 12 h
12 – 18 h
2– 3 days
Total CK
4–8h
12 – 24 h
2– 3 days
cTnT
4–9h
12 – 48 h
5 – 7 days
cTnI
4–9h
12 – 24 h
5 – 7 days
LDH
24-48 hrs
48-72 hrs
10-14 days
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MetabolismKULSOOM
of Homocysteine
THF
Methyl THF
Serine
Methionine
ATP
Pi + PPi
B12
Homocysteine
S-Adenosylmethionine
Adenosine
Methyl acceptor
B6
S-Adenosylhomocysteine
Methylated product
Cystathionine
-ketobutyrate
B6
Cysteine
THF = Tetrahydrofolate
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Elevated Homocysteine Levels Increase the Risk for
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Cardiovascular Disease
1
Homocysteine
injures the
arterial wall and
fatty substances
accumulate.
Circulating
monocytes rush
to the site of
injury causing
inflammation.
http://www.laddmcnamara.net/wp-content/uploads/2012/03/Homocysteine-Damage-Ladd-McNamara.jpg
2
3
Arterial wall cells
proliferate in an
effort to heal the
lesion, leading to
plaque
formation.
The normal levels of homocysteine should be less than 10 micromoles/L.
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C-reactive Protein (CRP), Fibrinogen & Amyloid A protein
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•  C-reactive protein
•  Fibrinogen
•  Amyloid A protein
Activation
certain
genes
Inflammation in
any part of the
body
IL-6
Increased risk of
cardiovascular Disease
•  C-reactive protein
•  Fibrinogen
•  Amyloid A protein
Inflammation in
atherosclerotic
plaque
• Markers of inflammation
• Favor more inflammation
• More coagulobility
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C-reactive Protein (CRP), Fibrinogen & Amyloid A protein
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CRP is a protein present in the blood (secreted by liver) that shows the presence of
inflammation in the body. Atherosclerosis is an inflammatory process. CRP can be a
marker of atherosclerosis and myocardial infarction.
Fibrinogen is a protein present in the blood that shows the predisposition to
thrombus formation. Atherosclerosis can rupture and lead to thrombus formation
which is the collection of fibrin meshwork of and platelets aggregation. Hence it can
be a marker of myocardial infarction.
Amyloid A a protein in the blood secreted by liver in response to the presence of
inflammation in the body. Amyloid A can be a marker of atherosclerosis.
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Atrial & Brain Natriuretic
Peptide(ANP)
• Atrial natriuretic peptide (ANP):
Secreted by atrial muscles in response to atrial distention due to any cause.
Normal levels: 3 + 0.3 p mol/L
• Brain natriuretic peptide(BNP):
Secreted by ventricular muscles stretching.
Normal values of BNP: <50 pg/ml
BNP: >100 pg/ml suggests congestive heart failure.
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http://www.ncbi.nlm.nih.gov/pubmed/8630708
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