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Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration
Published on: May 24, 2016
Integrin stimulation-induced hypertrophy in neonatal rat cardiomyocytes is NO-dependent
S Umar1, E J M van der Valk, M J Schalij
1Department of Cardiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. S.umar@lumc.nl
Molecular and Cellular Biochemistry
|August 12, 2008
Summary
Integrin stimulation, mimicking prolonged myocardial stretch, causes cardiomyocyte hypertrophy. This process is NO-dependent, unlike alpha(1)-adrenergic stimulation, highlighting a novel pathway in cardiac remodeling.
Area of Science:
- Cardiovascular Biology
- Cellular Mechanotransduction
- Integrin Signaling
Background:
- Prolonged myocardial stretch is a known trigger for cardiomyocyte hypertrophy.
- Integrins function as cellular receptors for mechanical stretch.
- The role of integrin signaling in initiating cardiomyocyte hypertrophy requires further elucidation.
Purpose of the Study:
- To investigate the hypothesis that integrin stimulation directly induces cardiomyocyte hypertrophy.
- To compare integrin-mediated hypertrophy with alpha(1)-adrenergic stimulation.
- To elucidate the signaling pathways involved in integrin-induced cardiomyocyte hypertrophy, particularly the role of nitric oxide synthase-1 (NOS1).
Main Methods:
- Neonatal rat cardiomyocytes (NRCMs) were treated with an Arg-Gly-Asp (RGD) peptide to stimulate integrins.
- Phenylephrine (PE) was used for alpha(1)-adrenergic stimulation; saline served as control.
- Cell surface area (CSA) quantified hypertrophy; NOS1 phosphorylation was assessed via immunocytochemistry; NOS inhibition (L-NAME), NO-donor, ryanodine, and BAPTA-AM were used to probe signaling.
Main Results:
- RGD peptide significantly increased NRCM cell surface area (CSA) by 38%, comparable to PE-induced hypertrophy (68%).
- Integrin stimulation by RGD markedly increased NOS1 phosphorylation (61%), while PE showed a smaller increase (21%).
- NOS inhibition completely blocked RGD-induced hypertrophy, which was partially restored by an NO-donor, indicating NO-dependence. Ryanodine and BAPTA-AM also abrogated RGD effects.
Conclusions:
- Integrin stimulation via RGD peptide induces cardiomyocyte hypertrophy in NRCMs.
- This integrin-induced hypertrophy is critically dependent on the activation of NOS1 and subsequent nitric oxide (NO) production.
- The signaling cascade initiated by integrin activation differs from that of alpha(1)-adrenergic stimulation, particularly concerning NO production and calcium handling.
