Discussions of troponin often pertain to its functional characteristics and/or to its usefulness as a diagnostic marker or therapeutic target for various heart disorders in particular as a highly specific marker for myocardial infarction or heart muscle cell death.
An increased level of the cardiac protein isoform of troponin circulating in the blood has been shown to be a biomarker of heart disorders, the most important of which is myocardial infarction. Raised Troponin levels indicate cardiac muscle cell death as the enzyme is released into the blood upon injury to the heart.
It is important to note that cardiac troponins are a marker of all heart muscle damage, not just myocardial infarction, which is the most severe form of heart disorder. However, diagnostic criteria for raised troponin indicating myocardial infarction is currently set by the WHO at a threshold of 2 ug or higher. Critical levels of other cardiac biomarkers are also relevant, such as Creatine Kinase. Other conditions that directly or indirectly lead to heart muscle damage and death can also increase troponin levels, such as renal failure Severe tachycardia (for example due to supraventricular tachycardia) in an individual with normal coronary arteries can also lead to increased troponins for example, it is presumed due to increased oxygen demand and inadequate supply to the heart muscle.
The distinction between cardiac and non-cardiac conditions is somewhat artificial; the conditions listed below are not primary heart diseases, but they exert indirect effects on the heart muscle.
Troponins are increased in around 40% of patients with critical illnesses such as sepsis. There is an increased risk of mortality and length of stay in the intensive-care unit in these patients. In severe gastrointestinal bleeding, there can also be a mismatch between oxygen demand and supply of the myocardium.
In hypertensive disorders of pregnancy such as preeclampsia, elevated troponin levels indicate some degree of myofibrillary damage.
Cardiac troponin T and I can be used to monitor drug and toxin-induced cardiomyocyte toxicity. .
Raised troponin levels are prognostically important in many of the conditions in which they are used for diagnosis.
In a community-based cohort study indicating the importance of silent cardiac damage, troponin I has been shown to predict mortality and first coronary heart disease event in men free from cardiovascular disease at baseline.
Due to patent regulations, a single manufacturer (Roche Diagnostics) distributes cTnT.
A host of diagnostic companies make cTnI immunoassay methods available on many different immunoassay platforms.
Troponin elevation following cardiac cell necrosis starts within 2-3 hours, peaks in approx. 24 hours, and persists for 1-2 weeks.
Troponin is attached to the protein tropomyosin and lies within the groove between actin filaments in muscle tissue. In a relaxed muscle, tropomyosin blocks the attachment site for the myosincrossbridge, thus preventing contraction. When the muscle cell is stimulated to contract by an action potential, calcium channels open in the sarcoplasmic membrane and release calcium into the sarcoplasm. Some of this calcium attaches to troponin, which causes it to change shape, exposing binding sites for myosin (active sites) on the actinfilaments. Myosin's binding to actin causes crossbridge formation, and contraction of the muscle begins.
Troponin activation. Troponin C (red) binds Ca2+, which stabilizes the activated state, where troponin I (yellow) is no longer bound to actin. Troponin T (blue) anchors the complex on tropomyosin.
Troponin is found in both skeletal muscle and cardiac muscle, but the specific versions of troponin differ between types of muscle. The main difference is that the TnC subunit of troponin in skeletal muscle has four calcium ion-binding sites, whereas in cardiac muscle there are only three. Views on the actual amount of calcium that binds to troponin vary from expert to expert and source to source.
In both cardiac and skeletal muscles, muscular force production is controlled primarily by changes in the intracellular calcium concentration. In general, when calcium rises, the muscles contract and, when calcium falls, the muscles relax.
Troponin is a component of thin filaments (along with actin and tropomyosin), and is the protein complex to which calcium binds to trigger the production of muscular force. Troponin itself has three subunits, TnC, TnI, and TnT, each of which playing a role in force regulation. Under resting intracellular levels of calcium, tropomyosin covers the active sites on actin to which myosin (a molecular motor organized in muscle thick filaments) binds in order to generate force. When calcium becomes bound to specific sites in the N-domain of TnC, a series of protein structural changes occurs such that tropomyosin is rolled away from myosin-binding sites on actin, allowing myosin to attach to the thin filament and produce force and/or shorten the sarcomere.
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