Novel troponin T mutation in familial dilated cardiomyopathy with gender-dependant severity

Stefanelli, Christopher B.; Rosenthal, Amnon; Borisov, Andrei B.; Ensing, Gregory J.; Russell, Mark W.

doi:10.1016/j.ymgme.2004.04.013

Cited by 35 publications

(18 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A female-over-male preference in induction of concentric cardiac hypertrophy was also observed in response to hemodynamic overload after myocardial infarction (18). Moreover, adult men demonstrate more severe ventricular dilatation and left ventricular dysfunction than adult women in familial dilated cardiomyopathy arising from cardiac troponin T mutation (34). Thus female sex hormones are likely to have a more beneficial rather than detrimental effect on adaptive responses of the heart to the pathophysiology of diabetes-induced cardiac dilatation.…”

Section: Discussionmentioning

confidence: 95%

Increased myocardial stiffness with maintenance of length-dependent calcium activation by female sex hormones in diabetic rats

Bupha-Intr

Wattanapermpool

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Bupha-Intr T, Oo YW, Wattanapermpool J. Increased myocardial stiffness with maintenance of length-dependent calcium activation by female sex hormones in diabetic rats. Am J Physiol Heart Circ Physiol 300: H1661-H1668, 2011. First published February 18, 2011 doi:10.1152/ajpheart.00411.2010.-A decrease in peak early diastolic filling velocity in postmenopausal women implies a sex hormonerelated diastolic dysfunction. The regulatory effect of female sex hormones on cardiac distensibility therefore was evaluated in ovariectomized rats by determining the sarcomere length-passive tension relationship of ventricular skinned fiber preparations. Diabetes also was induced in the rat to assess the protective significance of female sex hormones on diastolic function. While ovariectomy had no effect on myocardial stiffness, collagen content, or titin ratio, a significant increase in myocardial stiffness was observed in diabetic rat only when female sex hormones were intact. The increased stiffness in diabetic-sham rats was accompanied by an elevated collagen content resulting from increases in the levels of procollagen and Smad2. Surprisingly, the increased myocardial stiffness in diabetic-sham rats was accompanied by a shift toward a more compliant N2BA of cardiac titin isoforms. The pCa-active tension relationship was analyzed at fixed sarcomere lengths of 2.0 and 2.3 m to determine the magnitude of changes in myofilament Ca 2ϩ sensitivity between the two sarcomere lengths. Interestingly, high expression of N2BA titin was associated with a suppressed magnitude of changes in myofilament Ca 2ϩ sensitivity only in the diabetic-ovariectomized condition. Estrogen supplementation in diabetic-ovariectomized rats partially increased myocardial stiffness but completely reversed the change in myofilament Ca 2ϩ sensitivity. These results indicate a restrictive adaptation of myocardium governed by female sex hormones to maintain myofilament activity in compensation to the pathophysiological induction of cardiac dilatation by the diabetic condition. female sex hormones; diabetes; diastolic distension; titin; collagen THE REGULATORY ROLE OF FEMALE sex hormones on cardiac diastolic function has been indicated from reports showing a significant decrease in peak early diastolic velocity (E-wave) of the heart in postmenopausal women (1, 21). Of the two major factors affecting diastolic filling velocity, namely, relaxation and distension of myocardium, our previous studies in rats have demonstrated prolonged ventricular relaxation induced after chronic deprivation of ovarian sex hormones (8). A decrease in sarcoplasmic reticulum Ca 2ϩ uptake activity ultimately leads to a delayed decay of intracellular Ca 2ϩ level in cardiomyocytes of ovariectomized (OVX) rats, and Ca 2ϩ hypersensitivity of cardiac myofilament detected in such animals also impedes myocardial relaxation (7,8,41). A preventive effect of estrogen supplementation on all of these changes further supports the regulatory role of female sex hormones on ventricular relaxation (7,8)....

show abstract

Section: Discussionmentioning

confidence: 95%

Increased myocardial stiffness with maintenance of length-dependent calcium activation by female sex hormones in diabetic rats

Bupha-Intr

Wattanapermpool

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…In addition, a significant overlap of AF with several congenital disorders including dilated cardiomyopathy has been documented, with underlying mutations of genes encoding components of ion channels or, less frequently, structural proteins of the cytoskeleton and contractile apparatus [34]. There is also an increased appreciation of the phenotypic variability of these mutations, of which some result in significant gender differences, with adult males being more affected [35]. Some mutations could perhaps have an attenuated penetration, making an affected individual with apparently structurally normal heart particularly susceptible to tachyarrhythmia, with potentially deleterious effects on left ventricular systolic function, which promptly deteriorates in the setting of a high ventricular rate during AF.…”

Section: Discussionmentioning

confidence: 99%

Gender-related differences in presentation, treatment and long-term outcome in patients with first-diagnosed atrial fibrillation and structurally normal heart: The Belgrade atrial fibrillation study

Potpara

Marinković

Polovina

et al. 2012

International Journal of Cardiology

View full text Add to dashboard Cite

“…Functional studies of the mutation showed no change in the Ca 2+ sensitivity of force development or maximal force, and a decreased maximal actomyosin ATPase activity rate [8]. The Ala171Ser mutation was identified in a large multi-generation family with a history of autosomal dominant DCM [47]. This mutation is unique in the sense that for this particular family, the affected males tended to have more severe phenotypes than women.…”

Section: Dcm Associated Mutations In Tnmentioning

confidence: 97%

Sarcomeric Protein Mutations in Dilated Cardiomyopathy

2005

View full text Add to dashboard Cite

This review aims to provide a concise summary of the DCM associated mutations identified in the proteins of the sarcomere and cytoskeleton, and discuss the reported effects of the mutations, as determined by functional studies, and in relation to the known structure of the protein affected. The mechanisms by which single missense mutations in the proteins of the sarcomere can lead to similar diseases as those caused by mutations in the proteins of the sarcolemma and cytoskeleton, are still unknown. However, a wide variety of mutations being associated with DCM suggests a complex mechanism shared by the proteins affected. The DCM mutations reviewed here are those of the beta-myosin heavy chain (beta-MHC), myosin binding protein-C (MyBP-C), actin, alpha- tropomyosin (Tm), troponin T (TnT), troponin I (TnI), troponin C (TnC), of the sarcomere, and titin, T-cap, desmin, vinculin, and muscle LIM protein (MLP) of the cytoskeleton.

show abstract

Novel troponin T mutation in familial dilated cardiomyopathy with gender-dependant severity

Cited by 35 publications

References 25 publications

Increased myocardial stiffness with maintenance of length-dependent calcium activation by female sex hormones in diabetic rats

Increased myocardial stiffness with maintenance of length-dependent calcium activation by female sex hormones in diabetic rats

Gender-related differences in presentation, treatment and long-term outcome in patients with first-diagnosed atrial fibrillation and structurally normal heart: The Belgrade atrial fibrillation study

Sarcomeric Protein Mutations in Dilated Cardiomyopathy

Contact Info

Product

Resources

About