Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

Torrado, Mario; Iglesias, Raquel; Nespereira, Beatriz; Михайлов, А. И.

doi:10.1155/2010/603159

Cited by 11 publications

(13 citation statements)

References 34 publications

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“…Indeed, different quadrants of the mammalian heart (LV, RV, LA & RA) are divergent in structure, contractile function and metabolism as confirmed by compartment specific myocardial gene expression profiles [65]–[67]. Moreover, cardiac remodeling events that underlie important cardiovascular pathophysiologies vary in accordance with the specific heart compartments [67]–[69]. Hence, the influence of BPA on different anatomical subdivisions of the heart is presumed to be variable.…”

Section: Discussionmentioning

confidence: 99%

Maternal Bisphenol A Exposure Impacts the Fetal Heart Transcriptome

et al. 2014

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Conditions during fetal development influence health and disease in adulthood, especially during critical windows of organogenesis. Fetal exposure to the endocrine disrupting chemical, bisphenol A (BPA) affects the development of multiple organ systems in rodents and monkeys. However, effects of BPA exposure on cardiac development have not been assessed. With evidence that maternal BPA is transplacentally delivered to the developing fetus, it becomes imperative to examine the physiological consequences of gestational exposure during primate development. Herein, we evaluate the effects of daily, oral BPA exposure of pregnant rhesus monkeys (Macaca mulatta) on the fetal heart transcriptome. Pregnant monkeys were given daily oral doses (400 µg/kg body weight) of BPA during early (50–100±2 days post conception, dpc) or late (100±2 dpc – term), gestation. At the end of treatment, fetal heart tissues were collected and chamber specific transcriptome expression was assessed using genome-wide microarray. Quantitative real-time PCR was conducted on select genes and ventricular tissue glycogen content was quantified. Our results show that BPA exposure alters transcription of genes that are recognized for their role in cardiac pathophysiologies. Importantly, myosin heavy chain, cardiac isoform alpha (Myh6) was down-regulated in the left ventricle, and ‘A Disintegrin and Metalloprotease 12’, long isoform (Adam12-l) was up-regulated in both ventricles, and the right atrium of the heart in BPA exposed fetuses. BPA induced alteration of these genes supports the hypothesis that exposure to BPA during fetal development may impact cardiovascular fitness. Our results intensify concerns about the role of BPA in the genesis of human metabolic and cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Maternal Bisphenol A Exposure Impacts the Fetal Heart Transcriptome

et al. 2014

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“…Within the ventricular myocardium, myostatin expression is highest in the left ventricle, since a sixfold higher mRNA expression was measured there compared with the right ventricle of 20-day-old piglets (81). Interestingly, cardiac myostatin levels can be reinduced in the adult organism upon increased cardiac load.…”

Section: Cardiac Myostatin In Health and Diseasementioning

confidence: 97%

Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting

Breitbart

Auger‐Messier

Molkentin

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

104

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A significant proportion of heart failure patients develop skeletal muscle wasting and cardiac cachexia, which is associated with a very poor prognosis. Recently, myostatin, a cytokine from the transforming growth factor-β (TGF-β) family and a known strong inhibitor of skeletal muscle growth, has been identified as a direct mediator of skeletal muscle atrophy in mice with heart failure. Myostatin is mainly expressed in skeletal muscle, although basal expression is also detectable in heart and adipose tissue. During pathological loading of the heart, the myocardium produces and secretes myostatin into the circulation where it inhibits skeletal muscle growth. Thus, genetic elimination of myostatin from the heart reduces skeletal muscle atrophy in mice with heart failure, whereas transgenic overexpression of myostatin in the heart is capable of inducing muscle wasting. In addition to its endocrine action on skeletal muscle, cardiac myostatin production also modestly inhibits cardiomyocyte growth under certain circumstances, as well as induces cardiac fibrosis and alterations in ventricular function. Interestingly, heart failure patients show elevated myostatin levels in their serum. To therapeutically influence skeletal muscle wasting, direct inhibition of myostatin was shown to positively impact skeletal muscle mass in heart failure, suggesting a promising strategy for the treatment of cardiac cachexia in the future.

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“…In olfactory sensory neurons, CEP290 localizes to dendritic knobs [McEwen et al, 2007]. A recent study on differential gene expression in the ventricular myocardium of newborn piglets identified CEP290 as being threefold more enriched in the right compared with the left ventricle [Torrado et al, 2010]. Knockdown experiments in zebrafish using morpholinos caused defects reminiscent of JS, comprising retinal, cerebellar, and otic cavity developmental abnormalities as well as pronephric cyst formation, ectopic brain tissue in the fourth ventricle and an abnormal midto-hindbrain region associated with hydrocephalus Schafer et al, 2008].…”

Section: Biological Relevance Expressionmentioning

confidence: 99%

CEP290, a gene with many faces: mutation overview and presentation of CEP290base

et al. 2010

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Ciliopathies are an emerging group of disorders, caused by mutations in ciliary genes. One of the most intriguing disease genes associated with ciliopathies is CEP290, in which mutations cause a wide variety of distinct phenotypes, ranging from isolated blindness over SeniorLoken syndrome (SLS), nephronophthisis (NPHP), Joubert syndrome (related disorders) (JS[RD]), Bardet-Biedl syndrome (BBS), to the lethal Meckel-Grüber syndrome (MKS). Despite the identification of over 100 unique CEP290 mutations, no clear genotype-phenotype correlations could yet be established, and consequently the predictive power of a CEP290-related genotype remains limited. One of the challenges is a better understanding of second-site modifiers. In this respect, there is a growing interest in the potential modifying effects of variations in genes encoding other members of the ciliary proteome that interact with CEP290. Here, we provide an overview of all CEP290 mutations identified so far, with their associated phenotypes. To this end, we developed CEP290base, a locusspecific mutation database that links mutations with patients and their phenotypes (medgen.ugent.be/cep290base).

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Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

Cited by 11 publications

References 34 publications

Maternal Bisphenol A Exposure Impacts the Fetal Heart Transcriptome

Maternal Bisphenol A Exposure Impacts the Fetal Heart Transcriptome

Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting

CEP290, a gene with many faces: mutation overview and presentation of CEP290base

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