TABLE 3.

Release of cardiospecific Tns from CMC: mechanisms and diagnostic role.

Mechanism	Diagnostic value	Sources
CMC cell necrosis	This is the main proven mechanism underlying the increase in cardiospecific Tns in MI. CMC necrosis will result in the release of all molecules (biomarkers) from the cell into the bloodstream	Thygesen et al. (2012), Thygesen et al. (2018), Eckner et al. (2020)
Release of cardiospecific Tns as a result of the processes of regeneration and renewal of CMC	The renewal of CMC gradually occurring throughout life, hypothetically, may be associated with normal (less than the upper limit of the 99th percentile) concentrations of cardiospecific Tns in the bloodstream	Bergmann et al. (2009), White (2011), Bergmann et al. (2012)
Release of cardiospecific Tns as a result of apoptosis of CMC	It has been proven that apoptosis of CMC (without signs of necrosis) is accompanied by an increase in the serum concentration of cardiospecific Tns. Thus, any physiological (physical activity, old age) and pathological (HF, AH, COPD, etc.) conditions that enhance apoptosis may be accompanied by the release of cardiospecific Tns from CMC and an increase in serum levels	Cheng et al. (1995), Park et al. (2017), Felker and Fudim (2018), Weil et al. (2018), Gherasim (2019), Aengevaeren et al. (2021)
Release of cardiospecific Tns as a result of the formation of membrane vesicles on the surface of CMC	Membrane vesicles (blebbing vesicles) formed on the surface of the plasma membrane of CMC, hypothetically, may contain cytoplasmic proteins, including cardiospecific Tns. The number of membrane vesicles increases during ischemia of CMC and may be associated with the release of cardiospecific Tns into the bloodstream	Piper et al. (1984), Schwartz et al. (1984), Siegmund et al. (1990)
Intracellular proteolytic degradation of cardiospecific Tn molecules into small cardiospecific Tn fragments and the release of the latter through the intact membrane of CMC	Molecules of cardiospecific Tns can be fragmented/destroyed by the action of certain proteolytic enzymes: calpain, thrombin, matrix metalloproteinases. As a result of the action of these enzymes, there can form small fragments of cardiospecific Tn molecules, which, due to their size, have a higher probability of release from the cell. This mechanism may have high clinical significance: for example, all those physiological and pathological conditions and/or drugs that affect the activity of these proteolytic enzymes can also affect the release of cardiospecific Tns and their concentration in the bloodstream	Feng et al. (2001), Qun Gao et al. (2003), Lin et al. (2013), Streng et al. (2016), Katrukha et al. (2017), Parente et al. (2021)
Release of cardiospecific Tns as a result of increased membrane permeability of CMC	An increase in the release of cardiospecific Tn molecules into the bloodstream is observed in case of an increase in the membrane permeability of CMC, which is characteristic of myocardial ischemia, an increase in preload and stretching of the heart wall	Ross and Borg (2001), Thatte et al. (2004), Hessel et al. (2008), Khabbaz et al. (2008)
Release of cardiospecific Tns as a result of small-scale (subclinical) necrosis of CMC	The death of a small number of CMC may not manifest itself clinically and instrumentally (since these are relatively low-sensitivity methods), but HS methods of detection can register such subclinical lesions. Possible causes of subclinical necrosis of CMC are ischemia, inflammatory-toxic processes and imbalances in the neuroendocrine system	Martínez-Navarro et al. (2020), Marshall et al. (2020), O'Hanlon et al. (2010), Lazzarino et al. (2013)
Release of cardiospecific Tns from non-cardiac cells	This is a controversial mechanism of increased levels of cardiospecific Tns in the bloodstream. In the literature, there are works confirming the expression of cardiospecific Tns in skeletal muscle tissue in patients with CKD and hereditary skeletal myopathies, as well as studies that refute this hypothesis	Bodor et al. (1995), Messner et al. (2000), Hammerer-Lercher et al. (2001), Bakay et al. (2002), Rusakov et al. (2015a), Rusakov et al. (2015b), Schmid et al. (2018)