Interleukin-1 beta modulates the growth and phenotype of neonatal rat cardiac myocytes.

Thaik, Cynthia M.; Calderone, Angelino; Takahashi, Naoya; Colucci, Wilson S.

doi:10.1172/jci118095

Cited by 259 publications

(142 citation statements)

References 43 publications

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“…[ 3 H]Leucine Incorporation-Protein synthesis rate was determined as described (40,41). Briefly, neonatal cardiomyocytes were plated in 12-well plates at a density of 6 ϫ 10 5 /well in DMEM supplemented with 10% fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

Regulation of the Cell Surface Expression and Function of Angiotensin II Type 1 Receptor by Rab1-mediated Endoplasmic Reticulum-to-Golgi Transport in Cardiac Myocytes

Filipeanu¹,

Zhou²,

Claycomb

et al. 2004

Journal of Biological Chemistry

106

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Rab1GTPase coordinates vesicle-mediated protein transport specifically from the endoplasmic reticulum (ER) to the Golgi apparatus. We recently demonstrated that Rab1 is involved in the export of angiotensin II (Ang II) type 1 receptor (AT1R) to the cell surface in HEK293 cells and that transgenic mice overexpressing Rab1 in the myocardium develop cardiac hypertrophy. To expand these studies, we determined in this report whether the modification of Rab1-mediated ER-to-Golgi transport can alter the cell surface expression and function of endogenous AT1R and AT1R-mediated hypertrophic growth in primary cultures of neonatal rat ventricular myocytes. Adenovirus-mediated gene transfer of wild-type Rab1 (Rab1WT) significantly increased cell surface expression of endogenous AT1R in neonatal cardiomyocytes, whereas the dominant-negative mutant Rab1N124I had the opposite effect. Brefeldin A treatment blocked the Rab1WT-induced increase in AT1R cell surface expression. Fluorescence analysis of the subcellular localization of AT1R revealed that Rab1 regulated AT1R transport specifically from the ER to the Golgi in HL-1 cardiomyocytes. Consistent with their effects on AT1R export, Rab1WT and Rab1N124I differentially modified the AT1R-mediated activation of ERK1/2 and its upstream kinase MEK1. More importantly, adenovirus-mediated expression of Rab1N124I markedly attenuated the Ang II-stimulated hypertrophic growth as measured by protein synthesis, cell size, and sarcomeric organization in neonatal cardiomyocytes. In contrast, Rab1WT expression augmented the Ang II-mediated hypertrophic response. These data strongly indicate that AT1R function in cardiomyocytes can be modulated through manipulating AT1R traffic from the ER to the Golgi and provide the first evidence implicating the ERto-Golgi transport as a regulatory site for control of cardiomyocyte growth.

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Section: Methodsmentioning

confidence: 99%

Regulation of the Cell Surface Expression and Function of Angiotensin II Type 1 Receptor by Rab1-mediated Endoplasmic Reticulum-to-Golgi Transport in Cardiac Myocytes

Filipeanu¹,

Zhou²,

Claycomb

et al. 2004

Journal of Biological Chemistry

106

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“…IL-1 induces hypertrophy of cardiac myocytes in vitro, and inhibition of IL-1 attenuates acute inflammation and cardiac myocyte apoptosis after ischemia-reperfusion injury in rat hearts (10,13). Further, IL-1 expression correlates with left ventricular (LV) collagen content and LV end-diastolic diameter (LVEDD) after MI in rats and induces collagen gene transcription in fibroblasts (8,14).…”

mentioning

confidence: 99%

Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium

Murtuza

Suzuki

Bou‐Gharios

et al. 2004

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

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After myocardial infarction (MI), adverse remodeling with left ventricular (LV) dilatation is a major determinant of poor outcome. Skeletal myoblast (SkM) implantation improves cardiac function post-MI, although the mechanism is unclear. IL-1 influences post-MI hypertrophy and collagen turnover and is implicated in SkM death after grafting. We hypothesized that SkM expressing secretory IL-1 receptor antagonist (sIL-1ra) at MI border zones would specifically attenuate adverse remodeling and exhibit improved graft cell number. Stable murine male SkM lines (5 ؋ 10 5 cells), expressing or nonexpressing (cont) for sIL-1ra, were implanted into infarct border zones of female nude mice immediately after left coronary artery occlusion. LV ejection fraction (LVEF), end-diastolic diameter, and transmitral peak early͞late (E͞A) flow velocity ratio were determined by echocardiography. Cardiac myocyte hypertrophy and fibrosis were assessed by morphometry, picrosirius red staining, and hydroxyproline assay. At 3 weeks, cont-SkM-engrafted hearts showed reduced hypertrophy, improved LVEF (55.7 ؎ 1.2% vs. MI-only: 40.3 ؎ 2.9%), and preserved E͞A ratios. sIL-1ra-SkM implantation enhanced these effects (LVEF, 67.0 ؎ 2.3%) and significantly attenuated LV dilatation (LV end-diastolic diameter, 4.0 ؎ 1.1 mm vs. cont-SkM, 4.5 ؎ 1.2 mm vs. MI-only, 4.8 ؎ 1.8 mm); this was associated with greater graft numbers, as shown by PCR for male-specific smcy gene. Enzyme zymography showed attenuated matrix metalloproteinase-2 and -9 up-regulation post-MI by either donor SkM type, although infarct-remote zone collagen was reduced only with sIL-1ra-SkM. These results suggest that SkM implantation improves cardiac function post-MI by modulation of adverse remodeling, and that this effect can be significantly enhanced by targeting IL-1 as a key upstream regulator of both adverse remodeling and graft cell death.

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“…Cardiomyocytes were stimulated with angiotensin II (AT-II; 10 À6 mM) or endothelin-1 (10 À7 mM) in the absence or presence of beta-aminopropionitrile (BAPN; 100 mM), a LOX inhibitor, for 24 h. Then, the incorporation of [ 3 H] leucine in cells was measured as described by Thaik et al 18 …”

Section: Lox Enzyme Assay and Incorporation Of [ 3 H] Leucinementioning

confidence: 99%

Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice

et al. 2012

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Lysyl oxidase (LOX) and LOX-like protein-1 (LOXL-1) are extracellular matrix-embedded amine oxidases that have critical roles in the cross-linking of collagen and elastin. LOX family proteins are abundantly expressed in the remodeled heart of animals and humans and are implicated in cardiac fibrosis; however, their role in cardiac hypertrophy is unknown. In this study, in vitro stimulation with hypertrophic agonists significantly increased LOXL-1 expression, LOX enzyme activity and [ 3 H] leucine incorporation in neonatal rat cardiomyocytes. A LOX inhibitor, beta-aminopropionitrile (BAPN), inhibited agonist-induced leucine incorporation in cardiomyocytes in vitro, suggesting the involvement of LOXL-1 in cardiomyocyte hypertrophy. Abdominal aortic constriction in rats produced left ventricular hypertrophy in parallel with LOXL-1 mRNA upregulation. And BAPN administration significantly inhibited angiotensin II-induced cardiac hypertrophy in vivo. These results suggest a role of LOXL-1 in cardiac hypertrophy in vivo. We generated transgenic mice with cardiomyocyte-specific expression of LOXL-1. LOXL-1 transgenic mice pups were born normally and grew to adulthood without increased mortality; these mice exhibited a greater left ventricle to body weight ratio, larger myocyte diameter, and more brain natriuretic peptide expression than their wild-type littermates. Echocardiography revealed that the LOXL-1 transgenic mice also had greater wall thickness with preserved cardiac contraction. Our results indicate a possible fundamental role of LOXL-1 in cardiac hypertrophy.

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Interleukin-1 beta modulates the growth and phenotype of neonatal rat cardiac myocytes.

Cited by 259 publications

References 43 publications

Regulation of the Cell Surface Expression and Function of Angiotensin II Type 1 Receptor by Rab1-mediated Endoplasmic Reticulum-to-Golgi Transport in Cardiac Myocytes

Regulation of the Cell Surface Expression and Function of Angiotensin II Type 1 Receptor by Rab1-mediated Endoplasmic Reticulum-to-Golgi Transport in Cardiac Myocytes

Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium

Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice

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