Expression profiling of cardiac genes in human hypertrophic cardiomyopathy: insight into the pathogenesis of phenotypes

Lim, Steven; Roberts, Robert J.; Marian, A.J.

doi:10.1016/s1062-1458(02)00551-2

Cited by 43 publications

(65 citation statements)

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“…Changes in the expression levels have also been reported for mammalian FHL1, which is most highly expressed in skeletal muscle, with intermediate or lower expression in a wide range of tissues, including heart, lung, kidney, and brain (8,17). Its expression is upregulated in the cultured mouse skeletal muscle cell line C2C12 during differentiation in vitro (41), in rat hypertrophied skeletal muscle (32), in human heart in hypertrophic cardiomyopathy caused by transverse aortic constriction (30), and in mouse heart with dilated cardiomyopathy resulting from targeted deletion of muscle LIM protein (8). In contrast, FHL1 mRNA levels were found to be lowered in human ischemic dilated cardiomyopathy (68).…”

Section: Discussionmentioning

confidence: 83%

FHL5, a novel actin-binding protein, is highly expressed in eel gill pillar cells and responds to wall tension

Mistry

Kato²,

Tran³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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Supporting evidence for the contractile nature of fish branchial pillar cells was provided by demonstrating the presence of actin fibers and a novel four-and-a-half LIM (FHL) protein in which expression is specific for contractile tissues and sensitive to the tension applied to the pillar cell. When eel gill sections were stained with rhodamine-phalloidin, a selective fluorescent probe for fibrous actin, a strong bundle-like staining was observed around collagen columns in pillar cells, suggesting the presence of abundant actin fibers. A cDNA clone encoding a novel member of the actin-binding FHL family, FHL5, was isolated from a subtracted cDNA library of eel gill. Northern analysis revealed that FHL5 mRNA is highly expressed only in gills, heart, and skeletal muscle. In gills, FHL5 was found to be confined to pillar cells by immunohistochemistry. Confocal fluorescence microscopy showed that FHL5 is present in both cytosol and nucleus; within the cytosol, a large portion of FHL5 is colocalized with the phalloidin-positive actin bundles. Furthermore, transfection of myogenic C2C12 cells with FHL5 cDNA demonstrated, in addition to its interaction with actin stress fibers, a nuclear shuttling activity of FHL5. The mRNA and protein levels were found to be elevated on 1) transfer of eels from seawater to freshwater, 2) volume expansion by infusion of isotonic dextran-saline, and 3) constriction of gill vasculature by bolus injection of endothelin-1. These results suggest contractile nature of pillar cells and a role of FHL5 in maintaining the integrity and regulating the dynamics of pillar cells. C2C12 myoblast; endothelin; immunohistochemistry; lamella; zinc finger; four-and-a-half LIM FISH GILLS CONSIST OF a large number of filaments arranged along the gill arches. The surfaces of the filaments are greatly enlarged by a series of plate-like lamellae. Each lamella is composed of two sheets of epithelia separated by a thin space through which the blood circulates to allow the exchange of respiratory gases. The separation between the epithelial sheets is maintained by pillar cells and collagen bundles. Pillar cells are spool-shaped cells connecting two epithelial sheets of the respiratory lamella in fish gills (50,51,64). They are characterized by collagen bundles contained in the infoldings of the plasma membrane and are oriented perpendicularly to the epithelial sheets, which consist of a thin layer of pavement cells and a basal lamina that is continuous with the collagen bundles traversing the pillar cells (49, 64); for the anatomy of gill lamella, see the schematic illustration in Fig. 9D. The membrane-enclosed collagen bundles help prevent ballooning of the lamella. The inner surfaces of the two epithelial sheets are covered with flanges extended from the pillar cells, forming capillary lumen called lacunae. Another feature of the pillar cells is the presence of numerous myofilament-like structures that course through the cytoplasm in an orientation parallel to the collagen bundles. These myofilaments appear to ...

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Section: Discussionmentioning

confidence: 83%

FHL5, a novel actin-binding protein, is highly expressed in eel gill pillar cells and responds to wall tension

Mistry

Kato²,

Tran³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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“…51 Several developmental genes were upregulated in both stages of hypertrophy including skeletal a-actin 1, a well-recognized marker of cardiac hypertrophy, and the aforementioned DSCR1 and FGF1. Interestingly, there was also upregulation of two different regulators of muscle development, namely, four-and-a-half LIM domain 1 (FHL1), a LIM domain protein thought to play a role in skeletal muscle differentiation and identified earlier in genetic human hypertrophic cardiomyopathy, 52 and also a regulator of myogenesis interferon-related developmental regulator. 53 Changes in muscle contraction/cytoskeleton Reorganization of the actin cytoskeleton and an increase in contractile proteins constitute well-recognized responses of the heart to hypertrophy.…”

Section: Signal Transductionmentioning

confidence: 99%

Transcriptome of hypertension-induced left ventricular hypertrophy and its regression by antihypertensive therapies

et al. 2009

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Left ventricular hypertrophy (LVH), a common consequence of systemic hypertension associated with poor clinical outcome, is also a potentially reversible condition. Here, we probed the molecular pathways that underpin the development of LVH and their modulation by antihypertensive regimens that reversed LVH. Spontaneously hypertensive rats were studied at 12 (early LVH) and 48 weeks (late LVH), respectively, with normotensive Wistar-Kyoto rats as age-matched controls. Three treatment groups were maintained for 36 weeks on the following regimens: (1) quinapril, (2) doxazosin and quinapril combination, and (3) losartan. Gene expression profiling was performed with Affymetrix microarrays (GeneChip Rat-230A) and primary function-focused average linkage hierarchical cluster analysis. Of the 15 696 gene sequences expressed on the Affymetrix GeneChip Rat-230A, there was significant alteration in the expression of 295 (1.9%) of these transcripts in 'early' LVH and 143 (0.9%) in 'late' LVH. The predominant changes in gene expression were seen in metabolism, cell growth/proliferation, signal transduction, development and muscle contraction/cytoskeleton functional groups. Although sharing many effects on gene expression, the three treatments showed different expression profiles. Despite significant regression of LVH with treatment, 31 LVH-associated transcripts were unchanged by any of the treatment groups. Our data suggest that LVH regression does not normalize the LVH transcriptome. Therefore, regression of hypertension-induced LVH is associated with a distinct gene expression profile, suggesting the effect of both treatment and a previously unknown specific myocardial physiology after regression of LVH.

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“…These mutations are inherited in an autosomal dominant fashion with variable penetrance and age-related expression. 9) Cardiac arrhythmia is a common but manageable complication of HCM. Although supraventricular and ventricular tachycardias are common in HCM, they rarely cause complete AV block.…”

Section: Discussionmentioning

confidence: 99%

“…Eleven genes and around 150 mutations have been identified in the etiology of HCM. 9) We did not perform genetic analysis in the patients due to financial constraints. In a study on the genetics of HCM, a specific mutation concerning AV block in HCM was not identified.…”

Section: Discussionmentioning

confidence: 99%

“…In a study on the genetics of HCM, a specific mutation concerning AV block in HCM was not identified. 9) Therefore, this form of HCM may be caused by a new and unknown genetic mutation which causes dysfunction of the ion channels. Furthermore, myocardial ischemia, autonomic dysfunction, and an abnormal vascular response in HCM may be one of the underlying mechanisms for complete AV block.…”

Section: Discussionmentioning

confidence: 99%

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Abnormal His-Purkinje System Conduction Leading to Complete Atrioventricular Block in Patients With Hypertrophic Cardiomyopathy: A Report of 3 Cases

et al. 2004

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SUMMARYThis case report describes three hypertrophic cardiomyopathy patients with abnormal His-Purkinje conduction and complete atrioventricular block with attacks of syncope and cardiopulmonary arrest. Although arrhythmias are common in hypertrophic cardiomyopathy, complete atrioventricular block is very rare. Prolonged QRS duration and abnormal His-Purkinje system conduction may result in complete atrioventricular block. (Jpn Heart J 2004; 45: 347-352)

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Expression profiling of cardiac genes in human hypertrophic cardiomyopathy: insight into the pathogenesis of phenotypes

Cited by 43 publications

References 0 publications

FHL5, a novel actin-binding protein, is highly expressed in eel gill pillar cells and responds to wall tension

FHL5, a novel actin-binding protein, is highly expressed in eel gill pillar cells and responds to wall tension

Transcriptome of hypertension-induced left ventricular hypertrophy and its regression by antihypertensive therapies

Abnormal His-Purkinje System Conduction Leading to Complete Atrioventricular Block in Patients With Hypertrophic Cardiomyopathy: A Report of 3 Cases

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