Biomarkers in Cardiovascular System

1. Biomarkers in Cardiovascular System Dr. Bibi Kulsoom http://www.123rf.com/photo_9342517_cartoon-doctor-in-white-coat-attending-a-patient.html

2. Cardiovascular Biomarkers KULSOOM Cardio Blood • Substances that • Lead to • Involved in process of • Released as a result of • cardiovascular disease • Appearance of abnormal substances • and/OR • ed level of normal substances Detected or measured in blood as a marker Sampling Vascular http://www.highlands.edu/academics/divisions/scipe/biology/labs/cartersville/2122/diagrams/heartdiagram3.jpg

3. Cardiovascular Biomarkers: Serum Lipid KULSOOM Lipid profile: Normal Levels • LDL : < 100mg/dl • HDL: 40-60mg/dl • Total chol: <200mg/dl • Triglycerides: < 150 mg/dl TG VLDL LDL LDL Lipid profile: Abnormal • LDL • HDL • Total cholesterol • Triacylglycerol HDL Chol HDL Extra Chol Increased risk of CVS Disease HDL Blood vessel wall

4. Protein Biomarkers KULSOOM • Other Proteins • Apolipoprotein A • Apolipoprotein B • Troponin I • Troponin T • Myoglobin • Homocysteine (amino acid) • C-reactive Protein • Fibrinogen • Amyloid A • Brain Natriuretic Factor • Atrial Natriuretic Factor • Enzymes • Creatine Kinase • Lactate Dehydrogenase • Aspartate Transaminase (AST)

5. Creatine (Phospho) Kinase (CK, CPK) KULSOOM • Tissue location & Isoenzymes : Three isoenzymes found • CK-MM (97%): found in skeletal muscles • CK-MB(2%): found in cardiac muscles • CK-BB(traces): found in brain cells • Function: • Creatine phosphate quickly regenerates ATP in the tissues. • Arginine + Glycine + Methionine  Creatine. ATP ADP Creatine phosphate Creatine Creatine kinase

6. Creatine (Phospho) Kinase (CK, CPK) KULSOOM • 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, CK-MB activity: 0-15%

7. Lactate Dehydrogenase KULSOOM • 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.

8. Lactate Dehydrogenase KULSOOM • Function: • 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 NAD+ NADH Lactate Pyruvate Lactate dehydrogenase

9. Lactate Dehydrogenase KULSOOM • 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.

10. Aspartate Transaminase (AST) KULSOOM • 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.

11. Cardiovascular Biomarkers: Serum Apolipoproteins KULSOOM • Apolipoprotein A • Apolipoprotein B TG VLDL LDL •  Apolipoprotein A •  Apolipoprotein B LDL HDL Chol HDL Extra Chol Increased risk of cardiovascular Disease HDL Blood vessel wall

12. Troponins KULSOOM Troponin Tropomyosin Actin I C T http://jolisfukyu.tokai-sc.jaea.go.jp/fukyu/tayu/ACT04E/04/0406.htm http://img.tfd.com/mk/S/X2604-S-10.png

13. Troponins KULSOOM • 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 tropomyosinstrandforming a complex.

14. Troponin I & T KULSOOM • 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

15. Myoglobin KULSOOM • 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 CK-MB or troponin. • Raised in muscle damage (e.g. MI, skeletal muscle damage). • Normal levels in blood: < 80 ng/mL. http://www.nap.edu/books/0309064066/xhtml/images/img00013.jpg

16. Biomarkers Released in Blood after Myocardial Infarction KULSOOM Myoglobin Total CK LDH CK-MB Troponin I http://1.bp.blogspot.com/-ORQRvT9GZGM/Th7e0di7WhI/AAAAAAAAoKw/Ex7Cv5eba30/s1600/CardiacEnzymes.jpg

17. Biomarkers Released in Blood after Myocardial Infarction KULSOOM Troponin T Troponin I CK-MB & Total CK Myoglobin http://www.revespcardiol.org/sites/default/files/elsevier/images/255/255v56n07/grande/255v56n07-13049677tab04.gif

18. Biomarkers Released in Blood after Myocardial Infarction KULSOOM http://www.vetmed.vt.edu/education/Curriculum/VM8304/vet%20pathology/CASES/ISCHEMIA%202006/CARDIAC%20ENZYMES.jpg

19. Biomarkers Released in Blood after Myocardial Infarction KULSOOM

20. Metabolism of Homocysteine KULSOOM THF Methionine ATP Pi + PPi Methyl THF Serine Homocysteine S-Adenosylmethionine Adenosine Methyl acceptor Methylated product S-Adenosylhomocysteine Cystathionine B6 B12 B6 -ketobutyrate Cysteine THF = Tetrahydrofolate

21. Elevated Homocysteine Levels Increase the Risk for Cardiovascular Disease KULSOOM 3 2 Arterial wall cells proliferate in an effort to heal the lesion, leading to plaque formation. Circulating monocytes rush to the site of injury causing inflammation. 1 Homocysteine injures the arterial wall and fatty substances accumulate. http://www.laddmcnamara.net/wp-content/uploads/2012/03/Homocysteine-Damage-Ladd-McNamara.jpg The normal levels of homocysteine should be less than 10 micromoles/L.

22. C-reactive Protein (CRP), Fibrinogen & Amyloid A protein KULSOOM •  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

23. C-reactive Protein (CRP), Fibrinogen & Amyloid A protein KULSOOM 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.

24. Atrial & Brain Natriuretic Peptide(ANP) KULSOOM • 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: >100pg/ml suggests congestive heart failure. Thank You http://www.ncbi.nlm.nih.gov/pubmed/8630708