Release of cardiac troponin I from viable cardiomyocytes is mediated by integrin stimulation

Elevated cardiac troponin-I (cTnI) levels have been demonstrated in serum of patients without acute coronary syndromes, potentially via a stretch-related process. We hypothesize that this cTnI release from viable cardiomyocytes is mediated by stimulation of stretch-responsive integrins. Cultured cardiomyocytes were treated with (1) Gly–Arg–Gly–Asp–Ser (GRGDS, n = 22) to stimulate integrins, (2) Ser–Asp–Gly–Arg–Gly (SDGRG, n = 8) that does not stimulate integrins, or (3) phosphate-buffered saline (control, n = 38). Cells and media were analyzed for intact cTnI, cTnI degradation products, and matrix metalloproteinase (MMP)-2. Cell viability was examined by assay of lactate dehydrogenase (LDH) activity and by nuclear staining with propidium iodide. GRGDS-induced integrin stimulation caused increased release of intact cTnI (9.6 ± 3.0%) as compared to SDGRG-treated cardiomyocytes (4.5 ± 0.8%, p < 0.001) and control (3.0 ± 3.4%, p < 0.001). LDH release from GRGDS-treated cardiomyocytes (15.9 ± 3.8%) equalled that from controls (15.2 ± 2.3%, p = n.s.), indicating that the GRGDS-induced release of cTnI is not due to cell necrosis. This result was confirmed by nuclear staining with propidium iodide. Integrin stimulation increased the intracellular and extracellular MMP2 activity as compared to controls (both p < 0.05). However, despite the ability of active MMP2 to degrade cTnI in vitro, integrin stimulation in cardiomyocytes was not associated with cTnI degradation. The present study demonstrates that intact cTnI can be released from viable cardiomyocytes by stimulation of stretch-responsive integrins.

• Publication year

  2007

• Venue

  Pflügers Archiv: European Journal of Physiology

• Publication date

  2007-10-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1007/s00424-007-0354-8PMID 17909848PMCID 2226063
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Stretch-responsive integrin stimulation mediates the release of intact cTnI from viable cardiomyocytes.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• Integrin stimulation increased both intracellular and extracellular MMP-2 activity.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• LDH release and propidium iodide staining were consistent with preserved viability in GRGDS-treated cardiomyocytes, indicating the cTnI release was not explained by necrosis.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• GRGDS treatment increased release of intact cTnI from cultured cardiomyocytes compared with SDGRG and phosphate-buffered saline controls.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review

• grgds

  peptide, treatment

  A peptide containing the RGD motif used to stimulate integrins in cultured cardiomyocytes.

  Aliases: Gly-Arg-Gly-Asp-Ser

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• intact cardiac troponin i

  protein, biomarker

  The intact form of the cardiac contractile protein measured in cells and media.

  Aliases: cardiac troponin I, cTnI

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• integrin stimulation

  mechanism, cell signaling

  Activation of cardiomyocyte integrins by the RGD-containing peptide treatment.

  Aliases: stretch-responsive integrin stimulation

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• ldh release

  assay, viability marker

  An assay based on lactate dehydrogenase in the culture medium that is used to assess cell membrane damage.

  Aliases: lactate dehydrogenase release, LDH activity

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• mmp-2 activity

  enzyme activity, biochemical measure

  An enzymatic activity measured in the cardiomyocyte samples as an extracellular matrix protease readout.

  Aliases: matrix metalloproteinase-2, MMP2

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• propidium iodide staining

  staining method, assay

  A nuclear staining method used to identify cells with compromised membrane integrity.

  Aliases: propidium iodide, PI staining

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• sdgrg

  peptide, control

  A scrambled control peptide used in the cardiomyocyte experiments that does not stimulate integrins.

  Aliases: Ser-Asp-Gly-Arg-Gly

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• viable cardiomyocytes

  cell type, biological sample

  Cultured heart muscle cells used as the experimental cell model.

  Aliases: cardiomyocytes

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review

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