Molecular cloning of human cardiac troponin T isoforms: Expression in developing and failing heart

Re-Expression of Fetal Troponin Isoforms in the Postinfarction Failing Heart of the Rat.

“…In the failing human heart, it is not definite whether troponin isoform changes develop because results have been contradictory. Some studies 9,29 have shown a re-switching to the fetal pattern of troponin isoforms in the failing human heart with various etiologies, but others 21,23,30 found that re-switching occurred only in some circumstances.…”

Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies

“…Although TnT itself does not bind Ca 2+ , its allosteric effect on the troponin I (TnI)/troponin C (TnC) complex influences Ca 2+ sensitivity for tension development, depending on the concentration of Ca 2+ (82). The human heart expresses four TnT isoforms (cTnT 1 , cTnT 2 , cTnT 3 and cTnT 4 ) at the mRNA and protein levels; these are generated by an alternative splicing mechanism of the TnT gene (83)(84)(85). Isoform appearance is developmentally regulated: cTnT 3 predominates, while cTnT 4 is a minor (fetal) isoform in the adult human heart; the additional two fetal isoforms, cTnT 1 and cTnT 2 , are also present, but are barely detectable (86,87).…”

“…Isoform appearance is developmentally regulated: cTnT 3 predominates, while cTnT 4 is a minor (fetal) isoform in the adult human heart; the additional two fetal isoforms, cTnT 1 and cTnT 2 , are also present, but are barely detectable (86,87). Different studies have suggested that a significant amount of cTnT 4 is re-expressed in failing myocardium (84,85,87), which exhibits decreased myofibrillar ATPase activity (80,81,83) and a decrease in Ca 2+ sensitivity (88,89). Changes in the variable region of the cTnT molecule can alter interactions in the troponin complex; this may explain how a shift in cTnT isoforms alters myocardial contractility and Ca 2+ sensitivity of the cardiac contractile proteins (66,86).…”

“…Studies undertaken by Knott et al (79), Mesnard et al (86) and van der Velden et al (91) also failed to show any correlation between the pattern of cTnT isoform expression and failing myocardium, suggesting that increased cTnT 4 expression may not be a general characteristic of left ventricular failure. The controversy regarding the role of cTnT isoform changes in HF is further evidenced by results showing both increased and decreased expression of cTnT 1 in the failing heart (85,87).…”

Cardiac Troponin T Isoforms Affect the Ca2+ Sensitivity of Force Development in the Presence of Slow Skeletal Troponin I

“…During human heart development at least four isoforms of cardiac TnT (cTnT) 1 are expressed in a developmentally regulated manner (1,2). The expression level of the main fetal isoform, TnT isoform 1 (cTnT1), decreases and the expression of TnT isoform 3 (cTnT3) increases until cTnT3 becomes the only TnT isoform in the normal adult heart.…”