Cardiac biomarkers in acute coronary syndrome
K Sarat Chandra, AJ Swamy in Acute Coronary Syndromes, 2020
Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are more sensitive and specific markers than CK-MB in detecting myocardial necrosis and have become the preferred biomarkers for the diagnosis of AMI. Troponin is a complex of three proteins that is integral to muscle contraction in skeletal and cardiac muscle, regulating the calcium-mediated interaction between actin and myosin. Its three subunits are TnC, TnI and TnT. Troponin C binds to calcium ions in order to produce movement; troponin T binds to tropomyosin, interlocking it to form a troponin-tropomyosin complex; troponin I binds to actin in thin myofilaments to hold the troponin-tropomyosin complex in place. Troponin C has an identical amino-acid sequence in both skeletal and cardiac tissues and, thus, it has no potential as a cardiac specific marker. However, troponin T and troponin I have different isoforms in cardiac and skeletal muscle, encoded by separated genes, and consequently, have different amino-acid sequences. The respective cardiac isoforms of TnT (cTnT) and TnI (cTnI) allow production of antibodies that exclusively recognize these myocardial-specific proteins. Higher diagnostic sensitivity and specificity require specimen collection at patient presentation, 6–9 hours later and at 12–24 hours if clinical suspicion is high and earlier results are negative. Indeed, troponin is not considered as an early biomarker of myocardial necrosis: cardiac troponins need 4–10 hours after symptoms onset to appear in serum, and peak at 12–48 hours, remaining then abnormal for several days to two weeks [10–12].
Muscle
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella in Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
The predominant protein, actin, consists of spherical subunits (globular actin) arranged into two chains twisted around each other (fibrous actin). (Imagine two strands of pearls twisted around each other.) Tropomyosin is a long, thread-like protein found on the outer surface of the actin chain. Each tropomyosin molecule is associated with 6–7 actin subunits. The function of tropomyosin is to cover the binding sites for myosin on the actin subunits when the muscle is in the resting state. This prevents the interaction between actin and myosin that causes muscle contraction. Troponin is a smaller protein consisting of three subunits. One subunit binds to actin, another binds to tropomyosin and the third binds with calcium. When the muscle is relaxed, troponin holds the tropomyosin in its blocking position on the surface of the actin (see Figure 16.1, panel b).
Skeletal Muscle
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
A thin filament is about 5–6 nm in diameter, 1 µm long, and consists mainly of a strand of F-actin (F for fibrous), as illustrated in Figure 9.4b. A strand of F-actin is a polymer composed of two twisted rows of 300–400 individual molecules of G-actin (G for globular), each molecule having a diameter of about 5 nm and a molecular weight of about 42 kdaltons. The F-actin strand is held together by a thread of nebulin that extends along the F-actin between the two rows of G-actin molecules. Each G-actin molecule has an active site that can bind to the head of a myosin molecule but is prevented from doing so under resting conditions, when there is no contraction, by tropomyosin molecules that cover the active sites. A tropomyosin molecule is a double strand that joins head-to-tail with other tropomyosin molecules to form a twisted strand over the length of the F-actin. Each tropomyosin molecule covers seven active sites and is bound to a troponin molecule. A troponin molecule is composed of three largely globular subunits: (i) troponin T (tropomyosin-binding troponin) that forms a troponin-tropomyosin complex, (ii) troponin C (Ca2+ binding troponin) that plays a major role in contraction, as explained later, and (iii) troponin I (inhibitory troponin) that is attached to G-actin in the absence of Ca2+ and holds the tropomyosin in a position that blocks myosin from reaching the active sites on G-actin. When Ca2+ bind to troponin C, troponin I detaches from the actin, thereby allowing the tropomyosin to move over the surface of the thin filament.
Irreversible oxidative post-translational modifications in heart disease
Published in Expert Review of Proteomics, 2019
Tamara Tomin, Matthias Schittmayer, Sophie Honeder, Christoph Heininger, Ruth Birner-Gruenberger
Next to BNP, measurement of cardiac troponin T or I levels represent another routine diagnostic tool for addressing myocardial infarction and HF. The troponin complex is an important part of both skeletal and cardiac muscle regulating muscle contraction [37]. Historically necrosis of cardiomyocytes was believed to be the prime reason for release of cardiac troponins, however it was recently shown that other mechanisms can lead to a detectable elevation of cardiac troponin levels [38]. Pioneer studies from the late 1990s revealed a strong correlation between increased levels of cTnT and cTnI and risk of HF, paving their way into clinical diagnostics [39,40]. Clinical incorporation of cTnT as a marker for myocardial infarction and HF was facilitated by the development of high-sensitivity assays for cTnT (hs-cTnT) revealing a link between troponin T and poor prognosis of HF patients [41]. It is important to mention that special care has to be taken when addressing cTnT levels of patients with skeletal myopathies. Likely due to cross-reactivity of skeletal and cardiac troponin isoforms in commercial immunoassays, it has been recently shown that skeletal myopathies can also result in an apparent elevation of cTnT concentration [42].
High sensitivity troponins in contemporary cardiology practice: are we turning a corner?
Published in Expert Review of Cardiovascular Therapy, 2018
Mark Mariathas, Bartosz Olechowski, Michael Mahmoudi, Nick Curzen
Myofibrils are the basic contractile apparatus of myocytes. Each myofibril is composed of a thick and a thin filament. The thick filament is made up of myosin whilst actin makes up the thin filament. Troponins are classified as cardiac regulatory proteins that control the calcium-mediated interaction between actin and myosin. There are three subunits of the troponin complex: troponin C, I, and T [5]. Cardiac troponin I (cTnI) is cardiac-specific and, although cardiac troponin T can also be found in skeletal muscle, this subtype is not usually detected in currently available assays [6]. As a consequence, the measurement of cTn is considered to be extremely specific for cardiomyocyte injury [7]. It is this concept that has cemented the use of cTn assays in the modern diagnosis and management of acute coronary syndromes (ACS).
Incorporating molecular biomarkers into clinical practice for gastric cancer
Published in Expert Review of Anticancer Therapy, 2019
Shunsuke Nakamura, Mitsuro Kanda, Yasuhiro Kodera
Troponin I2 (TNNI2) is involved in calcium-sensitive regulation of contraction of cardiac and skeletal muscles and affects the composition of muscle fibers. TNN12 is highly expressed in fast skeletal muscles and is ubiquitously expressed in multiple tissues such as those of the gastrointestinal tract, liver, kidney, nerve system, and thyroid [20]. We found that TNNI2 is specifically overexpressed in GCs with potential to undergo peritoneal metastasis. TNNI2 mRNA is differentially expressed in tumor vs normal cells, and the levels of TNNI2 mRNA positively correlate with those of EMT-associated molecules tumor inhibitor of metalloproteinase 1 (TIMP1) and vacuolar protein sorting 13 homolog A (VPS13A). High levels of TNNI2 are significantly associated with younger age, pT4, stage, undifferentiated tumor, invasive growth, peritoneal metastasis, and positive peritoneal lavage cytology as well as poor prognosis [20]. Our findings suggest that TNNI2 expression in gastric tissues may serve as a specific biomarker that predicts metastasis of GC.
Related Knowledge Centers
- Acute Coronary Syndrome
- Muscle Contraction
- Myocardial Infarction
- Smooth Muscle
- Troponin C
- Troponin T
- Troponin I
- Cardiac Muscle
- Skeletal Muscle
- Regulation of Gene Expression