Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy

Vega, Rick B.; Rothermel, Beverly A.; Weinheimer, Carla J.; Kovács, Atilla; Naseem, R. Haris; Bassel‐Duby, Rhonda; Williams, R. Sanders; Olson, Eric N.

doi:10.1073/pnas.0237225100

Cited by 206 publications

(179 citation statements)

References 27 publications

Supporting

Mentioning

173

Contrasting

Order By: Relevance

“…Importantly, blockade to hypertrophy by MCIP overexpression does not result in cardiac decompensation, which supports the notion that strategies to prevent pathological hypertrophy will not necessarily be counterproductive (55,59,60). MCIP also plays a permissive role in calcineurin activation, the basis of which is incompletely understood (58). However, the inhibitory activity of MCIP toward calcineurin is dominant under conditions of MCIP overexpression.…”

Section: Figurementioning

confidence: 57%

See 1 more Smart Citation

Toward transcriptional therapies for the failing heart: chemical screens to modulate genes

McKinsey¹,

Olson²

2005

J. Clin. Invest.

Self Cite

117

View full text Add to dashboard Cite

In response to acute and chronic stresses, the heart frequently undergoes a remodeling process that is accompanied by myocyte hypertrophy, impaired contractility, and pump failure, often culminating in sudden death. The existence of redundant signaling pathways that trigger heart failure poses challenges for therapeutic intervention. Cardiac remodeling is associated with the activation of a pathological gene program that weakens cardiac performance. Thus, targeting the disease process at the level of gene expression represents a potentially powerful therapeutic approach. In this review, we describe strategies for normalizing gene expression in the failing heart with small molecules that control signal transduction pathways directed at transcription factors and associated chromatin-modifying enzymes.

show abstract

Section: Figurementioning

confidence: 57%

“…Overexpression of MCIP1 prevents pathological hypertrophy. Adapted with permission from Proceedings of the National Academy of Sciences of the United States of America (58,59). …”

Section: Figurementioning

confidence: 99%

Toward transcriptional therapies for the failing heart: chemical screens to modulate genes

McKinsey¹,

Olson²

2005

J. Clin. Invest.

Self Cite

117

View full text Add to dashboard Cite

show abstract

“…A role for CaMKII in meiosis resumption has not been explored in this organism; however, CaN has been implicated in the completion of meiosis through its regulator, Calcipressin (Horner et al, 2006;Takeo et al, 2006). Mutations in the Drosophila Calcipressin, sarah (sra), result in an anaphase I arrest with high levels of cyclin B (Horner et al, 2006;Takeo et al, 2006 (Fuentes et al, 2000;Kingsbury and Cunningham, 2000;Lee et al, 2004;Chan et al, 2005), but at endogenous levels, Calcipressin has a stimulatory effect on CaN activity (Hilioti and Cunningham, 2003;Vega et al, 2003). During Drosophila egg activation, it is likely that Sra acts to stimulate CaN activity, because CaN mutants also arrest at anaphase I (S. Takeo and T. Aigaki, personal communication).…”

Section: Meiosis Arrest and Release In Drosophilamentioning

confidence: 99%

Transitioning from egg to embryo: Triggers and mechanisms of egg activation

Horner

Wolfner

2008

Developmental Dynamics

183

177

View full text Add to dashboard Cite

The transition from mature oocyte to developing embryo requires a coordinated series of events, collectively known as egg activation. Egg activation includes changes to egg coverings to prevent polyspermy, release of oocyte meiotic arrest, generation of haploid female and male pronuclei, changes in maternal mRNAs and protein populations, and cytoskeletal rearrangements. In many animals, egg activation is triggered by fertilization, which increases intracellular calcium within the oocyte and thereby regulates molecular events of egg activation. In other animals, fertilization-independent external signals, including mechanical stimulation of eggs and/or changes in ionic milieu, trigger activation. Recent studies have clarified the upstream portion of pathways leading to eggshell changes and cell cycle resumption and have identified activation-induced changes in maternal mRNA and protein profiles that can identify molecular players in the downstream events of egg activation. We review signals that trigger activation and how they link to subsequent molecular events of egg activation. Developmental Dynamics 237:527-544, 2008.

show abstract

“…Given the recently identified role of calcineurin in hypertrophy (37), it is interesting that FN did not induce the expression of any of the isoforms of calcineurin or the calcineurin/NFATtarget gene Dscr1, which can be induced by mechanical stretch or adrenergic stimulation (49,53). On the other hand, FN induced calmodulin 1 (Supplemental Table S1), which activates calcineurin in response to elevated intracellular Ca 2ϩ levels.…”

Section: Fibronectin-induced Cardiomyocyte Hypertrophymentioning

confidence: 99%

Gene expression changes associated with fibronectin-induced cardiac myocyte hypertrophy

Chen

Huang

Stewart

et al. 2004

Physiological Genomics

View full text Add to dashboard Cite

(FN) is an extracellular matrix protein that binds to integrin receptors and couples cardiac myocytes to the basal lamina. Cardiac FN expression is elevated in models of pressure overload, and FN causes cultured cardiac myocytes to hypertrophy by a mechanism that has not been characterized in detail. In this study, we analyzed the gene expression changes induced by FN in purified rat neonatal ventricular myocytes using the Affymetrix RAE230A microarray, to understand how FN affects gene expression in cardiac myocytes and to separate the effects contributed by cardiac nonmyocytes in vivo. Pathway analysis using z-score statistics and comparison with a mouse model of cardiac hypertrophy revealed several pathways stimulated by FN in cardiac myocytes. In addition to the known cardiac myocyte hypertrophy markers, FN significantly induced metabolic pathways including virtually all of the enzymes of cholesterol biosynthesis, fatty acid biosynthesis, and the mitochondrial electron transport chain. FN also increased the expression of genes coding for ribosomal proteins, translation factors, and the ubiquitin-proteasome pathway. Interestingly, cardiac myocytes plated on FN showed elevated expression of the fibrosis-promoting peptides connective tissue growth factor (CTGF), WNT1 inducible signaling pathway protein 2 (WISP2), and secreted acidic cysteine-rich glycoprotein (SPARC). Our data complement in vivo studies and reveal several novel genes and pathways stimulated by FN, pointing to cardiac myocyte-specific mechanisms that lead to development of the hypertrophic phenotype. extracellular matrix; integrin; ventricular remodeling; signal transduction; gene expression profiling OUTSIDE-IN SIGNALING CHARACTERIZES the cellular effects mediated by interaction of cellular receptors with the extracellular matrix. In neonatal rat ventricular myocytes (NRVM), clustering of integrin receptors induced by fibronectin (FN) (39,40) or RGD peptides (3) elicits a hypertrophic response, characterized by a 1.5-to 3-fold increase in cellular area and corresponding increases in global mRNA and protein synthesis, together with enhanced myofibrillogenesis and sarcomeric assembly. FN also induces increased formation of focal adhesions and costameres, which are sites of contact of extracellular matrix with integrins and associated cytoskeletal proteins associated with the Z-disks of the sarcomere (39). As in other models of hypertrophy, the hypertrophic response is accompanied by changes in gene expression, with increased expression of the natriuretic peptides atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and fetal isoforms of sarcomeric proteins such as ␤-myosin heavy chain (␤MHC) and ␣-skeletal actin (␣SkA).The pathophysiological relevance of the FN-induced, integrin-mediated pathway is highlighted by the observation of increased deposition of FN in the extracellular matrix in animal models of cardiac hypertrophy and in patients with cardiac failure (5,20,22,29,42,45). The increased synthesis of FN is in part mediated...

show abstract

Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy

Cited by 206 publications

References 27 publications

Toward transcriptional therapies for the failing heart: chemical screens to modulate genes

Toward transcriptional therapies for the failing heart: chemical screens to modulate genes

Transitioning from egg to embryo: Triggers and mechanisms of egg activation

Gene expression changes associated with fibronectin-induced cardiac myocyte hypertrophy

Contact Info

Product

Resources

About