Troponin I gene expression during human cardiac development and in end-stage heart failure.

Sasse, Sarah K.; Brand, Nigel J.; Kyprianou, Phillip; Dhoot, Gurtej K.; Wade, Robert; Arai, M.; Periasamy, Muthu; Yacoub, Magdi H.; Barton, Paul J.R.

doi:10.1161/01.res.72.5.932

Cited by 232 publications

(141 citation statements)

References 46 publications

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“…Increased expression of Tnnt3 and Myl1 has previously been associated with cardiac stress or specific cardiomyopathies (17,18), suggesting that up-regulation of these genes in Prox1 mutants may represent a secondary defect. To determine whether Prox1 directly represses fast-twitch contractile protein gene expression in the heart, we performed chromatin immunoprecipitation (ChIP).…”

Section: Resultsmentioning

confidence: 99%

Loss ofProx1in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

Petchey¹,

Risebro²,

Vieira

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance How cardiac and skeletal muscle function is maintained and regulated is important in terms of understanding normal muscle physiology and muscle-based disease (myopathy). The two striated muscle types are structurally and functionally divergent, suggesting alternate molecular regulation. However, our discovery that the transcription factor Prox1 controls the same fast skeletal muscle gene program in both cardiac and slow skeletal muscle is significant in assigning a common genetic mechanism to striated muscle development. These studies establish a novel model of human dilated cardiomyopathy and reveal how loss of a single factor underpins conversion of slow to fast skeletal muscle, with implications for the molecular specification of endurance (stamina) versus rapidly contractile muscle function (speed).

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Section: Resultsmentioning

confidence: 99%

Loss ofProx1in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

Petchey¹,

Risebro²,

Vieira

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…The slow skeletal TnI is expressed in the hearts of embryos alongside cTnI [6]. At about 9 months after birth this expression pattern transitions to expression of cTnI alone [6,7].…”

Section: Structure and Function Of Cardiac Troponinsmentioning

confidence: 99%

“…The slow skeletal TnI is expressed in the hearts of embryos alongside cTnI [6]. At about 9 months after birth this expression pattern transitions to expression of cTnI alone [6,7]. The cTnT gene is expressed in the heart both in prenatal and postnatal periods, yet its expression is more complex in that it involves four main alternatively spliced transcripts (cTnT1 through cTnT4) that are numbered according to decreasing molecular weight.…”

Section: Structure and Function Of Cardiac Troponinsmentioning

confidence: 99%

High sensitivity cardiac troponin assays in the clinical laboratories

Jarolím

2015

Clinical Chemistry and Laboratory Medicine (CCLM)

115

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Abstract:Immunoassays measuring cardiac troponins I or T have become firmly established as critical tools for diagnosing acute myocardial infarction. While most contemporary assays provide adequate diagnostic performance, the increased sensitivity and precision of the new, high sensitivity assays that have already been introduced into clinical practice, provide the potential to further shorten intervals between blood draws or the time needed to detect the first significant troponin elevation. In addition to the relatively modest benefits at the diagnostic end, the high sensitivity assays and the investigational ultrasensitive cardiac troponin assays offer improvements for predicting major adverse cardiovascular events, development of heart failure or transition to end-stage kidney disease. These novel high sensitivity assays can measure troponin concentrations in 50%-100% of healthy individuals and therefore allow for the distribution of troponin values within a healthy cohort to be measured, patient's baseline troponin levels to be monitored, and clinicians to be alerted of deteriorating cardiorenal conditions. We envisage that the high sensitivity assays will become important tools for predicting each patient's risk of future adverse events and for guiding and monitoring corresponding adjustments of preventative therapeutic interventions.

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“…However, TnI isoforms also switch during the period of TnT isoform changes. Slow skeletal TnI (ssTnI) is the predominant TnI isoform throughout fetal life and gradually decreases during the first few months of postnatal development (10). Developmental down-regulation of ssTnI occurs even in the absence of cTnI.…”

mentioning

confidence: 99%

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

Gomes¹,

Venkatraman

Davis

et al. 2004

Journal of Biological Chemistry

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In this study we investigated the physiological role of the cardiac troponin T (cTnT) isoforms in the presence of human slow skeletal troponin I (ssTnI). ssTnI is the main troponin I isoform in the fetal human heart. In reconstituted fibers containing the cTnT isoforms in the presence of ssTnI, cTnT1-containing fibers showed increased Ca 2؉ sensitivity of force development compared with cTnT3-and cTnT4-containing fibers. The maximal force in reconstituted skinned fibers was significantly greater for the cTnT1 (predominant fetal cTnT isoform) when compared with cTnT3 (adult TnT isoform) in the presence of ssTnI. Troponin (Tn) complexes containing ssTnI and reconstituted with cTnT isoforms all yielded different maximal actomyosin ATPase activities. Tn complexes containing cTnT1 and cTnT4 (both fetal isoforms) had a reduced ability to inhibit actomyosin ATPase activity when compared with cTnT3 (adult isoform) in the presence of ssTnI. The rate at which Ca 2؉ was released from site II of cTnC in the cTnI⅐cTnC complex (122/s) was 12.5-fold faster than for the ssTnI⅐cTnC complex (9.8/s). Addition of cTnT3 to the cTnI⅐cTnC complex resulted in a 3.6-fold decrease in the Ca 2؉ dissociation rate from site II of cTnC. Addition of cTnT3 to the ssTnI⅐cTnC complex resulted in a 1.9-fold increase in the Ca 2؉ dissociation rate from site II of cTnC. The rate at which Ca 2؉ dissociated from site II of cTnC in Tn complexes also depended on the cTnT isoform present. However, the TnI isoforms had greater effects on the Ca 2؉ dissociation rate of site II than the cTnT isoforms. These results suggest that the different N-terminal TnT isoforms would produce distinct functional properties in the presence of ssTnI when compared with cTnI and that each isoform would have a specific physiological role in cardiac muscle.

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Troponin I gene expression during human cardiac development and in end-stage heart failure.

Cited by 232 publications

References 46 publications

Loss ofProx1in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

Loss ofProx1in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

High sensitivity cardiac troponin assays in the clinical laboratories

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

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