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Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene.[5][6] It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.

The TNNI3 gene encoding cardiac troponin I (cTnI) is located at 19q13.4 in the human chromosomal genome. Human cTnI is a 24 kDa protein consisting of 210 amino acids with isoelectric point (pI) of 9.87. cTnI is exclusively expressed in adult cardiac muscle.[7][8][9]

Gene evolution

Figure 1: A phylogenetic tree is derived from alignment of amino acid sequences.

cTnI has diverged from the skeletal muscle isoforms of TnI (slow TnI and fast TnI) mainly with a unique N-terminal extension. The amino acid sequence of cTnI is strongly conserved among mammalian species (Fig. 1). On the other hand, the N-terminal extension of cTnI has significantly different structures among mammal, amphibian and fish.[8]

Tissue distribution

TNNI3 is expressed as a heart specific gene.[8] Early embryonic heart expresses solely slow skeletal muscle TnI. cTnI begins to express in mouse heart at approximately embryonic day 10, and the level gradually increases to one-half of the total amount of TnI in the cardiac muscle at birth.[10] cTnI completely replaces slow TnI in the mouse heart approximately 14 days after birth [11]

Protein structure

Based on in vitrostructure-function relationship studies, the structure of cTnI can be divided into six functional segments:[12] a) a cardiac-specific N-terminal extension (residue 1–30) that is not present in fast TnI and slow TnI; b) an N-terminal region (residue 42–79) that binds the C domain of TnC; c) a TnT-binding region (residue 80–136); d) the inhibitory peptide (residue 128–147) that interacts with TnC and actin–tropomyosin; e) the switch or triggering region (residue 148–163) that binds the N domain of TnC; and f) the C-terminal mobile domain (residue 164–210) that binds actin–tropomyosin and is the most conserved segment highly similar among isoforms and across species. Partially crystal structure of human troponin has been determined.[13]

Posttranslational modifications

Phosphorylation
cTnI was the first sarcomeric protein identified to be a substrate of PKA.[14] Phosphorylation of cTnI at Ser23/Ser24 under adrenergic stimulation enhances relaxation of cardiac muscle, which is critical to cardiac function especially at fast heart rate. Whereas PKA phosphorylation of Ser23/Ser24 decreases myofilament Ca2+ sensitivity and increases relaxation, phosphorylation of Ser42/Ser44 by PKC increases Ca2+ sensitivity and decreases cardiac muscle relaxation.[15] Ser5/Ser6, Tyr26, Thr31, Ser39, Thr51, Ser77, Thr78, Thr129, Thr143 and Ser150 are also phosphorylation sites in human cTnI.[16]
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 (increasing contractility).[17] This is possible, because this modification decreases in the sensitivity to calcium, which in turn decreases the twitch and relaxation time. This, taken together with the fact that this stimuli often appears in during stress, makes serine 23 and 24 phosphorylation associated with the ‘fight or flight’ response.[18][19] Furthermore, the importance of modification is visible in serine 22 and 23, whose phosphorylation will impact the functions of the switch peptide with (modulate its interactions with cTnC).[20] This data highlights the importance of cTnI phosphorylation not only in the context of regulating interactions with other cellular components, but also plays a role in the structural interactions within the cTnI itself.
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.[21] cTnI has been shown to be phosphorylated by protein kinase A, protein kinase C, protein kinase G, and p21-activated kinase 3.[22]
A significant part of cTnI released into the patient’s bloodstream is phosphorylated.[23]
O-linked GlcNAc modification
Studies on isolated cardiomyocytes found increased levels of O-GlcNAcylation of cardiac proteins in hearts with diabetic dysfunction.[24] Mass spectrometry identified Ser150 of mouse cTnI as an O-GlcNAcylation site, suggesting a potential role in regulating myocardial contractility.
C-terminal truncation
The C-terminal end segment is the most conserved region of TnI.[25] As an allosteric structure regulated by Ca2+ in the troponin complex,[25][26][27] it binds and stabilizes the position of tropomyosin in low Ca2+ state[26][28] implicating a role in the inhibition of actomyosin ATPase. A deletion of the C-terminal 19 amino acids was found during myocardial ischemia-reperfusion injury in Langendorff perfused rat hearts.[29] It was also seen in myocardial stunning in coronary bypass patients.[30] Over-expression of the C-terminal truncated cardiac TnI (cTnI1-192) in transgenic mouse heart resulted in a phenotype of myocardial stunning with systolic and diastolic dysfunctions.[31] Replacement of intact cTnI with cTnT1-192 in myofibrils and cardiomyocytes did not affect maximal tension development but decreased the rates of force redevelopment and relaxation.[32]
Restrictive N-terminal truncation
The approximately 30 amino acids N-terminal extension of cTnI is an adult heart-specific structure.[33][34] The N-terminal extension contains the PKA phosphorylation sites Ser23/Ser24 and plays a role in modulating the overall molecular conformation and function of cTnI.[35] A restrictive N-terminal truncation of cTnI occurs at low levels in normal hearts of all vertebrate species examined including human and significantly increases in adaptation to hemodynamic stress[36] and Gsα deficiency-caused failing mouse hearts.[37] Distinct from the harmful C-terminal truncation, the restrictive N-terminal truncation of cTnI selectively removing the adult heart specific extension forms a regulatory mechanism in cardiac adaptation to physiological and pathological stress conditions.[38]

Pathologic mutations

Multiple mutations in cTnI have been found to cause cardiomyopathies.[39][40] cTnI mutations account for approximately 5% of familial hypertrophic cardiomyopathy cases and to date, more than 20 myopathic mutations of cTnI have been characterized.[16]

Clinical implications

The half-life of cTnI in adult cardiomyocytes is estimated to be ~3.2 days and there is a pool of unassembled cardiac TnI in the cytoplasm.[41] Cardiac TnI is exclusively expressed in the myocardium and is thus a highly specific diagnostic marker for cardiac muscle injuries, and cTnI has been universally used as indicator for myocardial infarction.[42] An increased level of serum cTnI also independently predicts poor prognosis of critically ill patients in the absence of acute coronary syndrome.[43][44]

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.[45][46]

In veterinary medicine, increased cTnI has been noted from myocardial damage after ionophore toxicity in cattle.[47]

High-sensitivity troponin I testing

The high sensitive troponin I (hs-cTnI) 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 revascularization, and cardiovascular death in asymptomatic people.[48][49][50][51][52]

High sensitive troponin I has been proven to have superior clinical performance versus high sensitivity troponin T in patients with renal impairment[53] and skeletal muscle disease.[54][55] It is also not affected by diurnal rhythm, which is important when the test is used as a screening tool for CVD.[56]

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.[57] 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.

  • High sensitive troponin I test can help to proactively identify individuals at high cardiovascular risk long before symptoms appear.[57][58] The higher the troponin I level in asymptomatic individuals, the higher the likelihood of subclinical myocardial injury.
  • It provides greater accuracy in identifying persons at low CVD risk.[58][57]
  • Troponin I is a biomarker that responds to treatment interventions. Reductions in troponin I levels proved to reduce the risk of future CVD.[59][60][61]
  • High sensitive troponin I used as a screening tool to assess a person’s cardiovascular risk and has the potential to reduce the growing cost burden of the healthcare system.[62]

The efficiency of the new test has been confirmed by data collected by international studies with the participation of more than 100,000 subjects.[63]

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 cardiovascular 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.[61]

Lateral-flow test

Lateral-flow tests (“rapid diagnostic kits”) have been developed for cardiac troponin I. The more basic kinds are qualitative and detect cTnI > 0.5 ng/L, sufficient to “rule in” serious cases in less than a minute.[64] More advanced types allow a quantitative readout using colorimetry, electrochemical fluorescence, or a magnetic detector.[65]

Notes

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000129991 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035458 – Ensembl, May 2017
  3. ^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Mogensen J, Kruse TA, Børglum AD (Jun 1998). “Assignment of the human cardiac troponin I gene (TNNI3) to chromosome 19q13.4 by radiation hybrid mapping”. Cytogenetics and Cell Genetics. 79 (3–4): 272–3. doi:10.1159/000134740. PMID 9605869.
  6. ^ Kimura A, Harada H, Park JE, Nishi H, Satoh M, Takahashi M, Hiroi S, Sasaoka T, Ohbuchi N, Nakamura T, Koyanagi T, Hwang TH, Choo JA, Chung KS, Hasegawa A, Nagai R, Okazaki O, Nakamura H, Matsuzaki M, Sakamoto T, Toshima H, Koga Y, Imaizumi T, Sasazuki T (Aug 1997). “Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy”. Nature Genetics. 16 (4): 379–82. doi:10.1038/ng0897-379. PMID 9241277. S2CID 31578767.
  7. ^ Bodor GS, Porterfield D, Voss EM, Smith S, Apple FS (Dec 1995). “Cardiac troponin-I is not expressed in fetal and healthy or diseased adult human skeletal muscle tissue”. Clinical Chemistry. 41 (12 Pt 1): 1710–5. doi:10.1093/clinchem/41.12.1710. PMID 7497610.
  8. ^ a b c Jin JP, Zhang Z, Bautista JA (2008). “Isoform diversity, regulation, and functional adaptation of troponin and calponin”. Critical Reviews in Eukaryotic Gene Expression. 18 (2): 93–124. doi:10.1615/critreveukargeneexpr.v18.i2.10. PMID 18304026.
  9. ^ 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.
  10. ^ Jin JP (Aug 1996). “Alternative RNA splicing-generated cardiac troponin T isoform switching: a non-heart-restricted genetic programming synchronized in developing cardiac and skeletal muscles”. Biochemical and Biophysical Research Communications. 225 (3): 883–9. Bibcode:1996BBRC..225..883J. doi:10.1006/bbrc.1996.1267. PMID 8780706.
  11. ^ Feng HZ, Hossain MM, Huang XP, Jin JP (Jul 2009). “Myofilament incorporation determines the stoichiometry of troponin I in transgenic expression and the rescue of a null mutation”. Archives of Biochemistry and Biophysics. 487 (1): 36–41. doi:10.1016/j.abb.2009.05.001. PMC 2752407. PMID 19433057.
  12. ^ Li MX, Wang X, Sykes BD (2004-01-01). “Structural based insights into the role of troponin in cardiac muscle pathophysiology”. Journal of Muscle Research and Cell Motility. 25 (7): 559–79. doi:10.1007/s10974-004-5879-2. PMID 15711886. S2CID 8973787.
  13. ^ PDB: 1J1E 1J1E​; Takeda S, Yamashita A, Maeda K, Maéda Y (Jul 2003). “Structure of the core domain of human cardiac troponin in the Ca(2+)-saturated form”. Nature. 424 (6944): 35–41. Bibcode:2003Natur.424…35T. doi:10.1038/nature01780. PMID 12840750. S2CID 2174019.
  14. ^ Stull JT, Brostrom CO, Krebs EG (Aug 1972). “Phosphorylation of the inhibitor component of troponin by phosphorylase kinase”. The Journal of Biological Chemistry. 247 (16): 5272–4. doi:10.1016/S0021-9258(19)44967-3. PMID 4262569.
  15. ^ Solaro RJ, van der Velden J (May 2010). “Why does troponin I have so many phosphorylation sites? Fact and fancy”. Journal of Molecular and Cellular Cardiology. 48 (5): 810–6. doi:10.1016/j.yjmcc.2010.02.014. PMC 2854207. PMID 20188739.
  16. ^ a b Sheng JJ, Jin JP (2014-01-01). “Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review”. Frontiers in Physiology. 5: 165. doi:10.3389/fphys.2014.00165. PMC 4012202. PMID 24817852.
  17. ^ 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.
  18. ^ Pi, YeQing; Kemnitz, Kara R.; Zhang, Dahua; Kranias, Evangelia G.; Walker, Jeffery W. (2002-04-05). “Phosphorylation of Troponin I Controls Cardiac Twitch Dynamics: Evidence From Phosphorylation Site Mutants Expressed on a Troponin I-Null Background in Mice”. Circulation Research. 90 (6): 649–656. doi:10.1161/01.RES.0000014080.82861.5F. ISSN 0009-7330.
  19. ^ Han, Dongju; Lim, Younghyun; Lee, Soah; Eyun, Seong-il (2025-12-31). “Troponin I – a comprehensive review of its function, structure, evolution, and role in muscle diseases”. Animal Cells and Systems. 29 (1): 446–468. doi:10.1080/19768354.2025.2533821. ISSN 1976-8354. PMC 12305882. PMID 40735528.
  20. ^ Hwang, Peter M.; Cai, Fangze; Pineda-Sanabria, Sandra E.; Corson, David C.; Sykes, Brian D. (2014-10-07). “The cardiac-specific N-terminal region of troponin I positions the regulatory domain of troponin C”. Proceedings of the National Academy of Sciences. 111 (40): 14412–14417. doi:10.1073/pnas.1410775111. ISSN 0027-8424.
  21. ^ 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)
  22. ^ 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.
  23. ^ 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.
  24. ^ Fülöp N, Mason MM, Dutta K, Wang P, Davidoff AJ, Marchase RB, Chatham JC (Apr 2007). “Impact of Type 2 diabetes and aging on cardiomyocyte function and O-linked N-acetylglucosamine levels in the heart”. American Journal of Physiology. Cell Physiology. 292 (4): C1370–8. doi:10.1152/ajpcell.00422.2006. PMID 17135297. S2CID 7165718.
  25. ^ a b Jin JP, Yang FW, Yu ZB, Ruse CI, Bond M, Chen A (Feb 2001). “The highly conserved COOH terminus of troponin I forms a Ca2+-modulated allosteric domain in the troponin complex”. Biochemistry. 40 (8): 2623–31. doi:10.1021/bi002423j. PMID 11327886.
  26. ^ a b Zhang Z, Akhter S, Mottl S, Jin JP (Sep 2011). “Calcium-regulated conformational change in the C-terminal end segment of troponin I and its binding to tropomyosin”. The FEBS Journal. 278 (18): 3348–59. doi:10.1111/j.1742-4658.2011.08250.x. PMC 3168705. PMID 21777381.
  27. ^ Wang H, Chalovich JM, Marriott G (2012-01-01). “Structural dynamics of troponin I during Ca2+-activation of cardiac thin filaments: a multi-site Förster resonance energy transfer study”. PLOS ONE. 7 (12) e50420. Bibcode:2012PLoSO…750420W. doi:10.1371/journal.pone.0050420. PMC 3515578. PMID 23227172.
  28. ^ Galińska A, Hatch V, Craig R, Murphy AM, Van Eyk JE, Wang CL, Lehman W, Foster DB (Mar 2010). “The C terminus of cardiac troponin I stabilizes the Ca2+-activated state of tropomyosin on actin filaments”. Circulation Research. 106 (4): 705–11. doi:10.1161/CIRCRESAHA.109.210047. PMC 2834238. PMID 20035081.,
  29. ^ McDonough JL, Arrell DK, Van Eyk JE (1999-01-08). “Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury”. Circulation Research. 84 (1): 9–20. doi:10.1161/01.res.84.1.9. PMID 9915770.
  30. ^ McDonough JL, Labugger R, Pickett W, Tse MY, MacKenzie S, Pang SC, Atar D, Ropchan G, Van Eyk JE (Jan 2001). “Cardiac troponin I is modified in the myocardium of bypass patients”. Circulation. 103 (1): 58–64. doi:10.1161/01.cir.103.1.58. PMID 11136686. S2CID 14065002.
  31. ^ Murphy AM, Kögler H, Georgakopoulos D, McDonough JL, Kass DA, Van Eyk JE, Marbán E (Jan 2000). “Transgenic mouse model of stunned myocardium”. Science. 287 (5452): 488–91. Bibcode:2000Sci…287..488M. doi:10.1126/science.287.5452.488. PMID 10642551.
  32. ^ Narolska NA, Piroddi N, Belus A, Boontje NM, Scellini B, Deppermann S, Zaremba R, Musters RJ, dos Remedios C, Jaquet K, Foster DB, Murphy AM, van Eyk JE, Tesi C, Poggesi C, van der Velden J, Stienen GJ (Oct 2006). “Impaired diastolic function after exchange of endogenous troponin I with C-terminal truncated troponin I in human cardiac muscle”. Circulation Research. 99 (9): 1012–20. doi:10.1161/01.RES.0000248753.30340.af. PMID 17023673. S2CID 22328470.
  33. ^ Perry SV (Jan 1999). “Troponin I: inhibitor or facilitator”. Molecular and Cellular Biochemistry. 190 (1–2): 9–32. doi:10.1023/A:1006939307715. PMID 10098965. S2CID 23721684.
  34. ^ Chong SM, Jin JP (May 2009). “To investigate protein evolution by detecting suppressed epitope structures”. Journal of Molecular Evolution. 68 (5): 448–60. Bibcode:2009JMolE..68..448C. doi:10.1007/s00239-009-9202-0. PMC 2752406. PMID 19365646.
  35. ^ Akhter S, Zhang Z, Jin JP (Feb 2012). “The heart-specific NH2-terminal extension regulates the molecular conformation and function of cardiac troponin I”. American Journal of Physiology. Heart and Circulatory Physiology. 302 (4): H923–33. doi:10.1152/ajpheart.00637.2011. PMC 3322736. PMID 22140044.
  36. ^ Yu ZB, Zhang LF, Jin JP (May 2001). “A proteolytic NH2-terminal truncation of cardiac troponin I that is up-regulated in simulated microgravity”. The Journal of Biological Chemistry. 276 (19): 15753–60. doi:10.1074/jbc.M011048200. PMID 11278823. S2CID 19133505.
  37. ^ Barbato JC, Huang QQ, Hossain MM, Bond M, Jin JP (Feb 2005). “Proteolytic N-terminal truncation of cardiac troponin I enhances ventricular diastolic function”. The Journal of Biological Chemistry. 280 (8): 6602–9. doi:10.1074/jbc.M408525200. PMID 15611140. S2CID 41228834.
  38. ^ Feng HZ, Chen M, Weinstein LS, Jin JP (Nov 2008). “Removal of the N-terminal extension of cardiac troponin I as a functional compensation for impaired myocardial beta-adrenergic signaling”. The Journal of Biological Chemistry. 283 (48): 33384–93. doi:10.1074/jbc.M803302200. PMC 2586242. PMID 18815135.
  39. ^ Seidman JG, Seidman C (Feb 2001). “The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms”. Cell. 104 (4): 557–67. doi:10.1016/s0092-8674(01)00242-2. PMID 11239412. S2CID 16788126.
  40. ^ Curila K, Benesova L, Penicka M, Minarik M, Zemanek D, Veselka J, Widimsky P, Gregor P (Feb 2012). “Spectrum and clinical manifestations of mutations in genes responsible for hypertrophic cardiomyopathy”. Acta Cardiologica. 67 (1): 23–9. doi:10.2143/AC.67.1.2146562. PMID 22455086.
  41. ^ Martin AF (Jan 1981). “Turnover of cardiac troponin subunits. Kinetic evidence for a precursor pool of troponin-I”. The Journal of Biological Chemistry. 256 (2): 964–8. doi:10.1016/S0021-9258(19)70073-8. PMID 7451483.
  42. ^ Januzzi JL, Filippatos G, Nieminen M, Gheorghiade M (Sep 2012). “Troponin elevation in patients with heart failure: on behalf of the third Universal Definition of Myocardial Infarction Global Task Force: Heart Failure Section”. European Heart Journal. 33 (18): 2265–71. doi:10.1093/eurheartj/ehs191. PMID 22745356.
  43. ^ Reynolds T, Cecconi M, Collinson P, Rhodes A, Grounds RM, Hamilton MA (Aug 2012). “Raised serum cardiac troponin I concentrations predict hospital mortality in intensive care unit patients”. British Journal of Anaesthesia. 109 (2): 219–24. doi:10.1093/bja/aes141. PMID 22617093.
  44. ^ Lee YJ, Lee H, Park JS, Kim SJ, Cho YJ, Yoon HI, Lee JH, Lee CT, Park JS (Apr 2015). “Cardiac troponin I as a prognostic factor in critically ill pneumonia patients in the absence of acute coronary syndrome”. Journal of Critical Care. 30 (2): 390–4. doi:10.1016/j.jcrc.2014.12.001. PMID 25534985.
  45. ^ Mannu GS, The non-cardiac use and significance of cardiac troponins. Scott Med J, 2014. 59(3): p. 172-8.
  46. ^ 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.
  47. ^ 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.
  48. ^ “Troponin”. Testing.com. 2021-01-27. Retrieved 2022-04-13.
  49. ^ 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.
  50. ^ 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.
  51. ^ 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.
  52. ^ 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.
  53. ^ 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.
  54. ^ 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.
  55. ^ 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.
  56. ^ 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.
  57. ^ a b c 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)
  58. ^ a b 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.
  59. ^ 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.
  60. ^ 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.
  61. ^ a b World Health Organization (2020). “The top 10 causes of death”.
  62. ^ 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)
  63. ^ “Kardioloģiskie marķieri – NMS laboratorija”. www.nms-laboratorija.lv. Retrieved 2022-03-10.
  64. ^ Schilling, Ellie; Sandman, Joy; Sait, Rida; Stich, April; Baryeh, Kwaku; Blankson, Gifty (July 2023). “An Undergraduate Independent Study Project: Using a Lateral Flow Assay to Detect Troponin”. Journal of College Science Teaching. 52 (6): 76–81. doi:10.1080/0047231X.2023.12315870.
  65. ^ Mohammadinejad, Arash; Nooranian, Samin; Kazemi Oskuee, Reza; Mirzaei, Sepideh; Aleyaghoob, Ghazaleh; Zarrabi, Ali; Selda Gunduz, Emine; Nuri Ertas, Yavuz; Sheikh Beig Goharrizi, Mohammad Ali (2 October 2024). “Development of Lateral Flow Assays for Rapid Detection of Troponin I: A Review”. Critical Reviews in Analytical Chemistry. 54 (7): 1936–1950. doi:10.1080/10408347.2022.2144995.

Further reading