Troponin I

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Troponin T
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Representation of the human heart troponin nuclear complex (52 kDa nucleus) band in calcium-saturated form. Blue = troponin C; green = troponic I; magenta = troponin T. Troponin Ribbon Diagram.png
Representation of the human heart troponin nuclear complex (52 kDa nucleus) band in calcium-saturated form. Blue = troponin C; green = troponic I; magenta = troponin T.
Troponin Troponino.svg
Troponin

Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex, where it binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place. Troponin I prevents myosin from binding to actin in relaxed muscle. When calcium binds to the troponin C, it causes conformational changes which lead to dislocation of troponin I. Afterwards, tropomyosin leaves the binding site for myosin on actin leading to contraction of muscle. The letter I is given due to its inhibitory character. It is a useful marker in the laboratory diagnosis of heart attack. [2] It occurs in different plasma concentration but the same circumstances as troponin T - either test can be performed for confirmation of cardiac muscle damage and laboratories usually offer one test or the other. [3]

Contents

Three paralogs with unique tissue-specific expression patterns are expressed in humans, listed below with their locations and OMIM accessions:

cTnI

Cardiac troponin I, often denoted as cTnI, is presented in cardiac muscle tissue by a single isoform with a molecular weight of 23.9 kDa. It consists of 209 amino acid residues. The theoretical pI of cTnI is 9.05. [4] cTnI differs from other troponins due to its N-terminal extension of 26 amino acids. This extension contains two serines, residues 23 and 24, which are phosphorylated by protein kinase A in response to beta-adrenergic stimulation and important in increasing the inotropic response. [5] Phosphorylation of cTnI changes the conformation of the protein and modifies its interaction with other troponins as well as the interaction with anti-TnI antibodies. These changes alter the myofilament response to calcium, and are of interest in targeting heart failure. Multiple reaction monitoring of human cTnI has revealed that there are 14 phosphorylation sites and the pattern of phosphorylation observed at these sites is changed in response to disease. [6] cTnI has been shown to be phosphorylated by protein kinase A, protein kinase C, protein kinase G, and p21-activated kinase 3. [7]

A significant part of cTnI released into the patient's blood stream is phosphorylated. [8] For more than 15 years cTnI has been known as a reliable marker of cardiac muscle tissue injury. It is considered to be more sensitive and significantly more specific in the diagnosis of myocardial infarction than the "golden marker" of the last decades – CK-MB, as well as total creatine kinase, myoglobin and lactate dehydrogenase isoenzymes.

Troponin I is not entirely specific for myocardial damage secondary to infarction. Other causes of raised troponin I include chronic kidney failure, heart failure, subarachnoid haemorrhage and pulmonary embolus. [9] [10]

In veterinary medicine, increased cTnI has been noted from myocardial damage after ionophore toxicity in cattle. [11]

High-sensitivity troponin I testing

The high sensitive troponin I test is a chemiluminescence microparticle immunoassay, which is used to quantitatively determine cardiac troponin I in human plasma and serum.  The test can be used to aid in diagnosing myocardial infarction, as a prognostic marker in patients with acute coronary syndrome and to identify the risk (low, moderate and elevated) of future cardiovascular diseases such as myocardial infarction, heart failure, ischaemic stroke, coronary revascularisation, and cardiovascular death in asymptomatic people. [12] [13] [14] [15] [16]

High sensitive troponin I has been proven to have superior clinical performance versus high sensitivity troponin T in patients with renal impairment [17] and skeletal muscle disease. [18] [19] It is also not affected by diurnal rhythm, which is important when the test is used as a screening tool for CVD. [20]

Prognostic use

The basis for the modern prevention of CVD lies in the prognosis of the risk of the development of myocardial infarction, stroke or heart failure in the future. Currently, most prognostic models of cardiovascular risk (European SCORE scale, Framingham scale, etc.) are based on the evaluation of traditional risk factors of CVD. This stratification system is indirect and has several limitations, which include the inaccurate forecasting of risks. [21] These risk scales are heavily dependent on the age of the person. Research data bears evidence that the high sensitive troponin I test enables higher precision in determining the cardiovascular risk group of the individual, if used together with the results of clinical and diagnostic examinations.

The efficiency of  the new test has been confirmed by data collected by international studies with the participation of more than 100,000 subjects. [27]

The ability of high sensitive troponin I to identify individual's cardiovascular risk in asymptomatic people enables physicians to use it in outpatient/ambulatory practice during preventive check-ups, complex health examinations, or examinations of patients with known risk factors. Knowing which cardiovascular risk group a person belongs to allows physicians to promptly determine patient care tactics well before the development of symptoms, and to prevent adverse outcomes.

Indications for testing

High sensitive troponin I test is recommended for asymptomatic women and men to assess and stratify their cardiovascular risk.

Individuals may or may not have known established cardio-vascular risk factors:

  1. high blood pressure;
  2. obesity;
  3. congenital factors, history of cardiovascular diseases;
  4. pre-diabetes, diabetes;
  5. sedentary lifestyle;
  6. metabolic syndrome;
  7. dislipidaemia;
  8. smoking.

Incorporating the high sensitive troponin I test into initial screening will improve the prediction of future CV events and help individuals be more compliant with lifestyle changes and possible medication recommended by their physician.

This might be a step forward for personalized preventive medicine, being especially relevant at an individual level, when clinicians need to weigh the importance of each risk factor and determine if the person needs therapy in addition to lifestyle advice.

The precise frequency of examinations is not pre-determined; it depends on the specific case, risk category and individual characteristics of a patient. The test may be added to the check-up programs or used as a stand along in conjunction with other clinical and diagnostic findings. [25]

History

Troponin was discovered in 1965. It was initially named heart myofibrillar apparatus protein component but was later renamed troponin. In 1971, Grieser and Gergely proved that troponin complex consists of three components, which, considering their specific properties, were named TnC, TnI and TnT. Over the following ten years, several groups of researchers started to demonstrate interest in the research of troponin, and the awareness of these proteins increased rapidly. When, finally, the amino acid sequences of troponin isoforms were determined, the opportunity to research functionally significant regions appeared. [28]

See also

Related Research Articles

<span class="mw-page-title-main">Coronary artery disease</span> Reduction of blood flow to the heart

Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of heart disease involving the reduction of blood flow to the cardiac muscle due to a build-up of atheromatous plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. CAD can cause stable angina, unstable angina, myocardial ischemia, and myocardial infarction.

<span class="mw-page-title-main">Troponin</span> Protein complex

Troponin, or the troponin complex, is a complex of three regulatory proteins that are integral to muscle contraction in skeletal muscle and cardiac muscle, but not smooth muscle. Measurements of cardiac-specific troponins I and T are extensively used as diagnostic and prognostic indicators in the management of myocarditis, myocardial infarction and acute coronary syndrome. Blood troponin levels may be used as a diagnostic marker for stroke or other myocardial injury that is ongoing, although the sensitivity of this measurement is low.

<span class="mw-page-title-main">Creatine kinase</span> Class of enzymes

Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phosphocreatine (PCr) and adenosine diphosphate (ADP). This CK enzyme reaction is reversible and thus ATP can be generated from PCr and ADP.

<span class="mw-page-title-main">Cardiac marker</span> Biomarkers relevant to heart function

Cardiac markers are biomarkers measured to evaluate heart function. They can be useful in the early prediction or diagnosis of disease. Although they are often discussed in the context of myocardial infarction, other conditions can lead to an elevation in cardiac marker level.

<span class="mw-page-title-main">Acute coronary syndrome</span> Dysfunction of the heart muscles due to insufficient blood flow

Acute coronary syndrome (ACS) is a syndrome due to decreased blood flow in the coronary arteries such that part of the heart muscle is unable to function properly or dies. The most common symptom is centrally located pressure-like chest pain, often radiating to the left shoulder or angle of the jaw, and associated with nausea and sweating. Many people with acute coronary syndromes present with symptoms other than chest pain, particularly women, older people, and people with diabetes mellitus.

<span class="mw-page-title-main">Unstable angina</span> Chest pain due to heart muscles that is easily provoked

Unstable angina is a type of angina pectoris that is irregular or more easily provoked. It is classified as a type of acute coronary syndrome.

<span class="mw-page-title-main">Troponin T</span> Protein family

Troponin T is a part of the troponin complex, which are proteins integral to the contraction of skeletal and heart muscles. They are expressed in skeletal and cardiac myocytes. Troponin T binds to tropomyosin and helps position it on actin, and together with the rest of the troponin complex, modulates contraction of striated muscle. The cardiac subtype of troponin T is especially useful in the laboratory diagnosis of heart attack because it is released into the blood-stream when damage to heart muscle occurs. It was discovered by the German physician Hugo A. Katus at the University of Heidelberg, who also developed the troponin T assay.

<span class="mw-page-title-main">Myocardial perfusion imaging</span> Nuclear medicine imaging method

Myocardial perfusion imaging or scanning is a nuclear medicine procedure that illustrates the function of the heart muscle (myocardium).

<span class="mw-page-title-main">TNNI3</span> Protein-coding gene in the species Homo sapiens

Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene. It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.

<span class="mw-page-title-main">TNNT2</span> Protein-coding gene in the species Homo sapiens

Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the TNNT2 gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.

<span class="mw-page-title-main">Troponin C type 1</span> Protein-coding gene in the species Homo sapiens

Troponin C, also known as TN-C or TnC, is a protein that resides in the troponin complex on actin thin filaments of striated muscle and is responsible for binding calcium to activate muscle contraction. Troponin C is encoded by the TNNC1 gene in humans for both cardiac and slow skeletal muscle.

The ST2 cardiac biomarker is a protein biomarker of cardiac stress encoded by the IL1RL1 gene. ST2 signals the presence and severity of adverse cardiac remodeling and tissue fibrosis, which occurs in response to myocardial infarction, acute coronary syndrome, or worsening heart failure.

<span class="mw-page-title-main">TNNI1</span> Protein-coding gene in the species Homo sapiens

Troponin I, slow skeletal muscle is a protein that in humans is encoded by the TNNI1 gene. It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.

<span class="mw-page-title-main">TNNI2</span> Protein-coding gene in the species Homo sapiens

Troponin I, fast skeletal muscle is a protein that in humans is encoded by the TNNI2 gene.

<span class="mw-page-title-main">TNNT1</span> Protein-coding gene in the species Homo sapiens

Slow skeletal muscle troponin T (sTnT) is a protein that in humans is encoded by the TNNT1 gene.

<span class="mw-page-title-main">Acadesine</span> Chemical compound

Acadesine (INN), also known as 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, AICA-riboside, and AICAR, is an AMP-activated protein kinase activator which is used for the treatment of acute lymphoblastic leukemia and may have applications in treating other disorders such as diabetes. AICAR has been used clinically to treat and protect against cardiac ischemic injury. The drug was first used in the 1980s as a method to preserve blood flow to the heart during surgery.

<span class="mw-page-title-main">Myocardial infarction</span> Interruption of cardiac blood supply

A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction to the heart muscle. The most common symptom is retrosternal chest pain or discomfort that classically radiates to the left shoulder, arm, or jaw. The pain may occasionally feel like heartburn. This is the dangerous type of Acute coronary syndrome.

<span class="mw-page-title-main">Heart-type fatty acid binding protein</span> Protein-coding gene in the species Homo sapiens

Heart-type fatty acid binding protein (hFABP) also known as mammary-derived growth inhibitor is a protein that in humans is encoded by the FABP3 gene.

A diagnosis of myocardial infarction is created by integrating the history of the presenting illness and physical examination with electrocardiogram findings and cardiac markers. A coronary angiogram allows visualization of narrowings or obstructions on the heart vessels, and therapeutic measures can follow immediately. At autopsy, a pathologist can diagnose a myocardial infarction based on anatomopathological findings.

Major adverse cardiovascular events is a composite endpoint frequently used in cardiovascular research. Despite widespread use of the term in clinical trials, the definitions of MACE can differ, which makes comparison of similar studies difficult.

References

  1. ↑ Takeda, Soichi; Yamashita, Atsuko; Maeda, Kayo; Maéda, Yuichiro (July 2003). "Structure of the core domain of human cardiac troponin in the Ca2+-saturated form". Nature. 424 (6944): 35–41. Bibcode:2003Natur.424...35T. doi:10.1038/nature01780. ISSN   1476-4687. PMID   12840750. S2CID   2174019.
  2. ↑ "Troponin". labtestsonline. 27 January 2021.
  3. ↑ "Troponin". labtestsonline.org/. 2019-01-09. Retrieved 2019-07-16.
  4. ↑ Kozlowski, LP (21 October 2016). "IPC - Isoelectric Point Calculator". Biology Direct. 11 (1): 55. doi: 10.1186/s13062-016-0159-9 . PMC   5075173 . PMID   27769290.
  5. ↑ Solaro RJ, Moir AJ, Perry SV (1976). "Phosphorylation of troponin I and the inotropic effect of adrenaline in the perfused rabbit heart". Nature. 262 (5569): 615–616. Bibcode:1976Natur.262..615S. doi:10.1038/262615a0. PMID   958429. S2CID   4216390.
  6. ↑ Zhang P, Kirk, JA, Ji W, dos Remedios CG, Kass DA, Van Eyk JE, Murphy AM (2012). "Multiple Reaction Monitoring to Identify Site-Specific Troponin I Phosphorylated Residues in the Failing Human Heart". Circulation. 126 (15): 1828–1837. doi:10.1161/circulationaha.112.096388. PMC   3733556 . PMID   22972900.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ↑ Layland J, Solaro RJ, Shah AM (2005). "Regulation of cardiac contractile function by troponin I phosphorylation". Cardiovascular Research. 66 (1): 12–21. doi: 10.1016/j.cardiores.2004.12.022 . PMID   15769444.
  8. ↑ Labugger R, Organ L, Collier C, Atar D, Van Eyk JE (2000). "Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction". Circulation. 102 (11): 1221–1226. doi: 10.1161/01.cir.102.11.1221 . PMID   10982534.
  9. ↑ Mannu GS, The non-cardiac use and significance of cardiac troponins. Scott Med J, 2014. 59(3): p. 172-8.
  10. ↑ Tanindi, Asil; Cemri, Mustafa (2011). "Troponin elevation in conditions other than acute coronary syndromes". Vascular Health and Risk Management. 7: 597–603. doi: 10.2147/VHRM.S24509 . PMC   3212425 . PMID   22102783.
  11. ↑ Smith, Joe S.; Varga, Anita; Schober, Karsten E. (2020). "Comparison of Two Commercially Available Immunoassays for the Measurement of Bovine Cardiac Troponin I in Cattle with Induced Myocardial Injury". Frontiers in Veterinary Science. 7: 531. doi: 10.3389/fvets.2020.00531 . PMC   7481330 . PMID   33062647.
  12. ↑ "Troponin". Testing.com. 2021-01-27. Retrieved 2022-04-13.
  13. ↑ Strandberg, Love S.; Roos, Andreas; Holzmann, Martin J. (2021-01-01). "Stable high-sensitivity cardiac troponin T levels and the association with frailty and prognosis in patients with chest pain". American Journal of Medicine Open. 1–6: 100001. doi: 10.1016/j.ajmo.2021.100001 . ISSN   2667-0364. PMC   11256254 . S2CID   244507759.
  14. ↑ Thygesen, Kristian; Alpert, Joseph S.; Jaffe, Allan S.; Chaitman, Bernard R.; Bax, Jeroen J.; Morrow, David A.; White, Harvey D. (2018-10-30). "Fourth Universal Definition of Myocardial Infarction (2018)". Journal of the American College of Cardiology. 72 (18): 2231–2264. doi: 10.1016/j.jacc.2018.08.1038 . hdl: 10044/1/73052 . ISSN   0735-1097. PMID   30153967. S2CID   52110825.
  15. ↑ Kerr, Gillian; Ray, Gautamananda; Wu, Olivia; Stott, David J.; Langhorne, Peter (2009). "Elevated troponin after a stroke: a systematic review". Cerebrovascular Diseases. 28 (3): 220–226. doi: 10.1159/000226773 . ISSN   1421-9786. PMID   19571535.
  16. ↑ Danese, E; Montagnana, M (2016). "An historical approach to the diagnostic biomarkers of acute coronary syndrome". Annals of Translational Medicine. 4 (10): 194. doi: 10.21037/atm.2016.05.19 . PMC   4885896 . PMID   27294090.
  17. ↑ Gunsolus, I (2017). "Renal Dysfunction Influences the Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin I". Journal of the American Society of Nephrology. 29 (2): 636–643. doi:10.1681/asn.2017030341. PMC   5791068 . PMID   29079658.
  18. ↑ Jaffe, A.S.; et al. (2011). "Diseased skeletal muscle: a noncardiac source of increased circulating concentrations of cardiac troponin T". Journal of the American College of Cardiology. 58 (17): 1819–1824. doi: 10.1016/j.jacc.2011.08.026 . PMID   21962825. S2CID   25530497.
  19. ↑ Wens, S.C.A.; et al. (2016). "Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease". Circulation: Cardiovascular Genetics. 9 (1): 6–13. doi: 10.1161/CIRCGENETICS.115.001322 . PMID   26787432. S2CID   10306074.
  20. ↑ Klinkenberg, L.J.J.; et al. (2016). "Diurnal Rhythm of Cardiac Troponin: Consequences for the Diagnosis of Acute Myocardial Infarction". Clinical Chemistry. 62 (12): 1602–1611. doi: 10.1373/clinchem.2016.257485 . PMID   27707754.
  21. 1 2 3 Farmakis, D., Mueller, C., Apple, F.S. (2020). "High-sensitivity cardiac troponin assays for cardiovascular risk stratification in the general population". European Heart Journal. 41 (41): 4050–4056. doi:10.1093/eurheartj/ehaa083. PMID   32077940.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. 1 2 Sigurdardottir, F.D.; et al. (2018). "Relative Prognostic Value of Cardiac Troponin I and C-Reactive Protein in the General Population (from the Nord-Trøndelag Health [HUNT] Study)". The American Journal of Cardiology. 121 (8): 949–955. doi:10.1016/j.amjcard.2018.01.004. hdl: 10852/97228 . PMID   29496193.
  23. ↑ Ford, I.; et al. (2016). "High-Sensitivity Cardiac Troponin, Statin Therapy, and Risk of Coronary Heart Disease". Journal of the American College of Cardiology. 68 (25): 2719–2728. doi:10.1016/j.jacc.2016.10.020. PMC   5176330 . PMID   28007133.
  24. ↑ Everett, B.M.; et al. (2015). "High-sensitivity cardiac troponin I and B-type natriuretic Peptide as predictors of vascular events in primary prevention: impact of statin therapy". Circulation. 131 (21): 1851–1860. doi:10.1161/circulationaha.114.014522. PMC   4444427 . PMID   25825410.
  25. 1 2 World Health Organization (2020). "The top 10 causes of death".
  26. ↑ Jülicher, P., Varounis, C. (2022). "Estimating the cost-effectiveness of screening a general population for cardiovascular risk with high-sensitivity troponin-I". European Heart Journal - Quality of Care & Clinical Outcomes. 8 (3): 342–351. doi:10.1093/ehjqcco/qcab005. PMC   9071558 . PMID   33502472.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ↑ "Kardioloģiskie marķieri – NMS laboratorija". www.nms-laboratorija.lv. Retrieved 2022-03-10.
  28. ↑ Fuster, V., Kelly, B.B. (2010). Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. National Academies Press.{{cite book}}: CS1 maint: multiple names: authors list (link)
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