Changes in IGFs in cardiac tissue following myocardial infarction

Matthews, Ken; Devlin, G.; Conaglen, JV; Stuart, SP; Aitken, W Mervyn; Bass, J. J.

doi:10.1677/joe.0.1630433

Cited by 29 publications

(29 citation statements)

References 38 publications

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“…Indeed, elevated IGF-1 correlates with improved recovery of postischemic hearts. 1,[13][14][15] Our studies have shown that Igf-1 ϩ/Ϫ transgenic mouse hearts are resistant to apoptosis or necrosis in 3 different models of ischemia, confirming the disease-resistant phenotype of these hearts. However, the Igf-1 ϩ/Ϫ mice also have side effects that include an age-dependent hypertrophy and hyperplasia of the heart and various other organs that appears within the first year of life and may compromise the protective effects of IGF-1 in older mice.…”

Section: Discussionsupporting

confidence: 66%

“…12 Other work has shown that the endogenous PI3-kinase pathway is activated in the postinfarcted myocardium, where it may contribute to cell survival and hypertrophy. [13][14][15] Regulation of the endogenous PI3-kinase pathway during I/R has not been described. We report here that Igf-1 ϩ/Ϫ transgenic mouse hearts are resistant to I/R-mediated apoptosis through a novel pathway involving enhanced basal activation of Akt and superinduction by reperfusion.…”

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confidence: 99%

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Reperfusion-Activated Akt Kinase Prevents Apoptosis in Transgenic Mouse Hearts Overexpressing Insulin-Like Growth Factor-1

Yamashita

Kajstura

Discher

et al. 2001

Circulation Research

139

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Abstract-Hearts of wild-type and insulin-like growth factor-1 overexpressing (Igf-1 ϩ/Ϫ ) transgenic mice were subjected to Langendorff perfusions and progressive periods of ischemia followed by reperfusion. Apoptosis was measured by DNA nucleosomal cleavage and a hairpin probe labeling assay to detect single-base overhang. Transgenic hearts subjected to 20 minutes of ischemia and 4 hours of reperfusion (I/R) sustained a rate of apoptosis of 1.8Ϯ0.3% compared with 4.6Ϯ1.1% for wild-type controls (nϭ4; PϽ0.03). Phosphorylation of the protein kinase Akt/protein kinase B was elevated 6.2-fold in transgenic hearts at baseline and increased another 4.4-fold within 10 minutes of reperfusion, remaining elevated for up to 2 hours. I/R activated Akt in wild-type hearts but to a lesser extent (1.6Ϯ0.3-fold). Pretreatment of transgenic hearts with wortmannin immediately before and during ischemia eliminated reperfusionmediated activation of Akt and neutralized the resistance to apoptosis. The stress-activated kinase p38 was also activated during ischemia and reperfusion in both wild-type and transgenic hearts. Perfusion with the p38 inhibitor SB203580 (10 mol/L) blocked both p38 activation and phosphorylation of Akt and differentially modulated apoptosis in wild-type and transgenic hearts. Pretreatment with SB203580 reduced apoptosis in wild-type hearts but increased apoptosis in transgenic hearts. These results demonstrate that Akt phosphorylation during I/R is modulated by IGF-1 and prevents apoptosis in hearts that overexpress the IGF-1 transgene. (Circ Res. 2001;88:609-614.) Key Words: ischemia Ⅲ hypoxia Ⅲ phosphoinositol-3Ј-kinase Ⅲ p38 mitogen-activated protein kinase Ⅲ SB203580 P rotective and antiapoptotic properties of insulin-like growth factor-1 (IGF-1) have been demonstrated in different models of myocardial ischemia and infarction 1-4 as well as in isolated cardiac myocytes subjected to ischemic or oxidative stress. 5,6 IGF-1 stimulates the phosphoinositol-3Ј (PI3)-kinase pathway, producing phosphoinositides that promote activation of the kinase Akt. 7,8 Activated Akt kinase plays a central role in suppressing apoptosis by modulating the activities of Bcl-2 family proteins, 9 caspase 9, 10 and Fas ligand. 11 Transfer of mutationally activated PI3-kinase and Akt genes has been shown to prevent apoptosis of cardiac myocytes in vitro, 6 and activated Akt delivered by an adenovirus vector reduced apoptosis in the intact heart subjected to ischemia and reperfusion (I/R). 4 We previously reported that Igf-1 ϩ/Ϫ transgenic mice overexpressing IGF-1 had reduced rates of necrosis and apoptosis after myocardial infarction caused by coronary artery ligation. 3 The same hearts were also resistant to necrosis but not apoptosis caused by nonocclusive coronary artery constriction. 12 Other work has shown that the endogenous PI3-kinase pathway is activated in the postinfarcted myocardium, where it may contribute to cell survival and hypertrophy. [13][14][15] Regulation of the endogenous PI3-kinase pathway during I/R has not b...

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Section: Discussionsupporting

confidence: 66%

mentioning

confidence: 99%

Reperfusion-Activated Akt Kinase Prevents Apoptosis in Transgenic Mouse Hearts Overexpressing Insulin-Like Growth Factor-1

Yamashita

Kajstura

Discher

et al. 2001

Circulation Research

139

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“…74 The expression of IGF-1 also is enhanced after experimental infarction in surviving cardiomyocytes. 75 These data suggest activation of the PAPP-A/IGF-1 system as part of a very early response to ischemia 76 aimed at increasing delivery of IGF-1 to jeopardized tissues. 77…”

Section: Igf-1 Papp-a and Early Response To Ischemiamentioning

confidence: 95%

Insulin-Like Growth Factor-1 as a Vascular Protective Factor

Conti¹,

Carrozza²,

Capoluongo³

et al. 2004

Circulation

227

162

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“…30 IGF-1 (Insulin-like Growth Factor-1) is normally associated with growth and proliferation signaling cascades via binding to its plasma membrane receptor (IGF-1R), and cardiomyocyte IGF-1 signaling represents an early cellular response mechanism in myocardial hypertrophy and injury. 31,32 In a study of rat atrial tissue, LVA Ca 2+ currents, Ca V 3.1 and Ca V 3.2 mRNAs were all regulated in parallel with IGF-1 and IGF-1R mRNA levels, leading the authors to suggest that IGF-1 may be associated with the T-type Ca 2+ channel increases observed during pressure overload or following myocardial infarction. 33 In the same study, cultured rat atrial myocytes showed selective induction of T-type, but not L-type Ca 2+ currents in an IGF-1 dependent manner.…”

Section: Regulation Of T-type Ca 2+ Channels By Hormonal Stimulimentioning

confidence: 99%

T-type calcium channel expression and function in the diseased heart

Cribbs¹

2010

Channels

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Changes in IGFs in cardiac tissue following myocardial infarction

Cited by 29 publications

References 38 publications

Reperfusion-Activated Akt Kinase Prevents Apoptosis in Transgenic Mouse Hearts Overexpressing Insulin-Like Growth Factor-1

Reperfusion-Activated Akt Kinase Prevents Apoptosis in Transgenic Mouse Hearts Overexpressing Insulin-Like Growth Factor-1

Insulin-Like Growth Factor-1 as a Vascular Protective Factor

T-type calcium channel expression and function in the diseased heart

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