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Administration of a Synthetic Peptide Derived from the E-domain Region of Mechano-Growth Factor Delays Decompensation Following Myocardial Infarction.

ABSTRACT: Insulin like growth factor-I (IGF-1) isoforms differ structurally in their E-domain regions and their temporal expression profile in response to injury. We and others have reported that Mechano-growth factor (MGF), which is equivalent to human IGF-1c and rodent IGF-1Eb isoforms, is expressed acutely following myocardial infarction (MI) in the mouse heart. To examine the function of the E-domain region, we have used a stabilized synthetic peptide analog corresponding to the unique 24 amino acid region E-domain of MGF. Here we deliver the human MGF E-domain peptide to mice during the acute phase (within 12 hours) and the chronic phase (8 weeks) post-MI. We assessed the impact of peptide delivery on cardiac function and cardiovascular hemodynamics by pressure-volume (P-V) loop analysis and gene expression by quantitative RT-PCR. A significant decline in both systolic and diastolic hemodynamics accompanied by pathologic hypertrophy occurred by 10 weeks post-MI in the untreated group. Delivery of the E-domain peptide during the acute phase post-MI ameliorated the decline in hemodynamics, delayed decompensation but did not prevent pathologic hypertrophy. Delivery during the chronic phase post-MI significantly improved systolic function, predominantly due to the effects on vascular resistance and prevented decompensation. While pathologic hypertrophy persisted there was a significant decline in atrial natriuretic factor (ANF) expression in the E-domain peptide treated hearts. Taken together our data suggest that administration of the MGF E-domain peptide derived from the propeptide form of IGF-1Ec may be used to facilitate the actions of IGF-I produced by the tissue during the progression of heart failure to improve cardiovascular function.

SUBMITTER: Shioura K

PROVIDER: S-EPMC4297642 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Administration of a Synthetic Peptide Derived from the E-domain Region of Mechano-Growth Factor Delays Decompensation Following Myocardial Infarction.

Shioura Km K Pena Jr J Goldspink Ph P

International journal of cardiovascular research 20140601 3

Insulin like growth factor-I (IGF-1) isoforms differ structurally in their E-domain regions and their temporal expression profile in response to injury. We and others have reported that Mechano-growth factor (MGF), which is equivalent to human IGF-1c and rodent IGF-1Eb isoforms, is expressed acutely following myocardial infarction (MI) in the mouse heart. To examine the function of the E-domain region, we have used a stabilized synthetic peptide analog corresponding to the unique 24 amino acid r ...[more]

PMID: 25606570

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Project description:BackgroundPreclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans.Methods and resultsOverall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI.ConclusionsThe presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254.

Dataset Information

Administration of a Synthetic Peptide Derived from the E-domain Region of Mechano-Growth Factor Delays Decompensation Following Myocardial Infarction.

Publications

Administration of a Synthetic Peptide Derived from the E-domain Region of Mechano-Growth Factor Delays Decompensation Following Myocardial Infarction.

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