Sarcomeric protein isoform transitions in cardiac muscle: A journey to heart failure

Yin, Zhiyong; Ren, Jun; Guo, Wei

doi:10.1016/j.bbadis.2014.11.003

Cited by 95 publications

(98 citation statements)

References 86 publications

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“…We found greater enrichment of differentially expressed genes in structural genes, including reductions in T-tubule factors Dysf, Trim72, Obscn, Trdn, and Tcap, than for Ca 2+ -handling or ion channel pathway genes ( Figure 6). Reexpression of embryonically expressed myosins, actins, and troponins is common in failing hearts, and forced expression of these isoforms in mature cardiomyocytes generally perturbs contractility (51). The majority of heritable HCM and DCM cases are due to mutations within sarcomeric genes that affect cardiomyocyte sarcomeric organization, contractile properties, and/or Ca 2+ sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Ectopic expression of Cdk8 induces eccentric hypertrophy and heart failure

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Ectopic expression of Cdk8 induces eccentric hypertrophy and heart failure

et al. 2017

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“…99 The sarcomeric proteins myosin, actin, troponin, tropomyosin and titin show isoform switching during development as a result of distinct gene expression or alternative splicing. 100 During HF, isoform transitions occur, often with re-induction of the fetal gene program. In addition, calcium transients are different in neonates, with increased utilization of trans-sarcolemmal calcium flux.…”

Section: Shared Mechanismsmentioning

confidence: 99%

Heart Failure in Pediatric Patients With Congenital Heart Disease

Hinton

Ware

2017

Circulation Research

142

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Heart failure (HF) is a complex clinical syndrome resulting from diverse primary and secondary causes, and shared pathways of disease progression, correlating with substantial mortality, morbidity and cost. HF in children is most commonly attributable to coexistent congenital heart disease (CHD), with different risks depending on the specific type of malformation. Current management and therapy for HF in children are extrapolated from treatment approaches in adults. This review discusses the causes, epidemiology and manifestations of HF in children with CHD, and presents the clinical, genetic and molecular characteristics that are similar or distinct from adult HF. The objective of this review is to provide a framework for understanding rapidly increasing genetic and molecular information in the challenging context of detailed phenotyping. We review clinical and translational research studies of HF in CHD including at the genome, transcriptome, and epigenetic levels. Unresolved issues and directions for future study are presented.

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“…7). Although there are four Mybpc genes in the mammalian genome, only cardiac Mybpc (Mybpc3) is expressed in embryonic, neonatal, and adult hearts (8,9). Cardiac MYBPC interacts with at least four sarcomere components: myosin heavy chain, actin, myosin light chain 2, and titin (10)(11)(12).…”

mentioning

confidence: 99%

Cardiac myosin binding protein C regulates postnatal myocyte cytokinesis

Jiang

Burgon

Wakimoto

et al. 2015

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

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Homozygous cardiac myosin binding protein C-deficient (Mybpc t/t ) mice develop dramatic cardiac dilation shortly after birth; heart size increases almost twofold. We have investigated the mechanism of cardiac enlargement in these hearts. Throughout embryogenesis myocytes undergo cell division while maintaining the capacity to pump blood by rapidly disassembling and reforming myofibrillar components of the sarcomere throughout cell cycle progression. Shortly after birth, myocyte cell division ceases. Cardiac MYBPC is a thick filament protein that regulates sarcomere organization and rigidity. We demonstrate that many Mybpc t/t myocytes undergo an additional round of cell division within 10 d postbirth compared with their wild-type counterparts, leading to increased numbers of mononuclear myocytes. Short-hairpin RNA knockdown of Mybpc3 mRNA in wild-type mice similarly extended the postnatal window of myocyte proliferation. However, adult Mybpc t/t myocytes are unable to fully regenerate the myocardium after injury. MYBPC has unexpected inhibitory functions during postnatal myocyte cytokinesis and cell cycle progression. We suggest that human patients with homozygous MYBPC3-null mutations develop dilated cardiomyopathy, coupled with myocyte hyperplasia (increased cell number), as observed in Mybpc t/t mice. Human patients, with heterozygous truncating MYBPC3 mutations, like mice with similar mutations, have hypertrophic cardiomyopathy. However, the mechanism leading to hypertrophic cardiomyopathy in heterozygous MYBPC3 +/− individuals is myocyte hypertrophy (increased cell size), whereas the mechanism leading to cardiac dilation in homozygous Mybpc3 −/− mice is primarily myocyte hyperplasia.myosin binding protein C | cardiac dilation | cardiac hypertrophy | cytokinesis | hyperplasia

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Sarcomeric protein isoform transitions in cardiac muscle: A journey to heart failure

Cited by 95 publications

References 86 publications

Ectopic expression of Cdk8 induces eccentric hypertrophy and heart failure

Ectopic expression of Cdk8 induces eccentric hypertrophy and heart failure

Heart Failure in Pediatric Patients With Congenital Heart Disease

Cardiac myosin binding protein C regulates postnatal myocyte cytokinesis

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