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KULSOOM Biomarkers in Cardiovascular System Dr. Bibi Kulsoom

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Presentation on theme: "KULSOOM Biomarkers in Cardiovascular System Dr. Bibi Kulsoom"— Presentation transcript:

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

2 KULSOOM http://www.highlands.edu/academics/divisions/scipe/biology/labs/cartersville/2122/diagrams/heartdiagram3.jpg Cardio Vascular 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 Blood KULSOOM Cardiovascular Biomarkers

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

4 KULSOOM Enzymes – Creatine Kinase – Lactate Dehydrogenase – Aspartate Transaminase (AST) 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 KULSOOM Protein Biomarkers

5 KULSOOM Creatine phosphate Creatine Creatine kinase ATPADP KULSOOM 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: Creatine phosphate quickly regenerates ATP in the tissues. Arginine + Glycine + Methionine  Creatine.

6 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% KULSOOM Creatine (Phospho) Kinase (CK, CPK)

7 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. KULSOOM Lactate Dehydrogenase

8 KULSOOM PyruvateLactate Lactate dehydrogenase NAD + NADH KULSOOM Lactate Dehydrogenase  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

9 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. KULSOOM Lactate Dehydrogenase

10 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. KULSOOM Aspartate Transaminase (AST)

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

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

13 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 tropomyosin strand forming a complex. KULSOOM Troponins

14 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 KULSOOM Troponin I & T

15 KULSOOM 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 A protein which stores oxygen inside muscle tissue (cardiac, skeletal & smooth). KULSOOM Myoglobin

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

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

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

19 KULSOOM MARKERDETECTIONPEAKDISAPPEARANCE Myoglobin1 – 4 h6 – 7h24h CK-MB mass3 – 12 h12 – 18 h2– 3 days Total CK4 – 8 h 12 – 24 h2– 3 days cTnT4 – 9 h12 – 48 h5 – 7 days cTnI4 – 9 h12 – 24 h5 – 7 days LDH24-48 hrs48-72 hrs10-14 days KULSOOM Biomarkers Released in Blood after Myocardial Infarction

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

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

22 KULSOOM  C-reactive protein  Fibrinogen  Amyloid A protein Increased risk of cardiovascular Disease Inflammation in atherosclerotic plaque Inflammation in any part of the body IL-6  C-reactive protein  Fibrinogen  Amyloid A protein Markers of inflammation Favor more inflammation More coagulobility Activation certain genes KULSOOM C-reactive Protein (CRP), Fibrinogen & Amyloid A protein

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

24 KULSOOM Brain natriuretic peptide(BNP): Secreted by ventricular muscles stretching. Normal values of BNP: <50 pg/ml BNP: >100 pg/ml suggests congestive heart failure. 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 http://www.ncbi.nlm.nih.gov/pubmed/8630708 KULSOOM Atrial & Brain Natriuretic Peptide(ANP)


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