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Updated: Oct 9, 2026
Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery
Published on: December 23, 2014
Expression of Q227L-Galpha(s) inhibits intimal vessel wall hyperplasia after balloon injury
W Holness1, T A Santore, G P Brown
1Departments of Pharmacology, Medicine, and Pathology, and the Cardiovascular Research Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Abstract:
Interaction between signaling pathways regulates many cellular functions, including proliferation. The Galpha(s)/cAMP pathway is known to inhibit signal flow from receptor tyrosine kinases to mitogen-activated protein kinase (MAPK)-1,2 and, thus, inhibit proliferation. Elevation of cAMP or adenovirus-directed expression of mutant (Q227L)-Galpha(s) (alpha(s)*) inhibits the proliferation of rat vascular smooth muscle cells (VSMCs) in culture. Platelet-derived growth factor (PDGF) stimulated MAPK activation and DNA synthesis was also blocked by expression of alpha(s)*. However, it is not known whether such mechanisms are operative in vivo. Proliferation of vascular smooth muscle cells in vivo was induced by balloon injury of carotid arteries in the rat. Recombinant adenovirus encoding beta-galactosidase (beta-gal) or alpha(s)* was applied to arterial segments injured by the balloon catheters. The alpha(s)*-treated vessels showed decreased phospho-MAPK staining in the intima as compared with beta-gal-treated vessels. Application of alpha(s)*, but not beta-gal containing adenovirus, inhibited formation of neointima by 50%. No change was observed in total vessel diameter or in the media or adventitia. These results suggest that the interaction between the Galpha(s) and MAPK pathways can regulate proliferation in vivo and that targeted expression of activated Galpha(s) may have therapeutic potential for the treatment of vascular pathophysiologies that arise from intimal hyperplasia.
Insights
The Galpha(s)/cAMP pathway inhibits vascular smooth muscle cell proliferation. Activated Galpha(s) reduced neointima formation in injured rat arteries, suggesting therapeutic potential for vascular diseases.
Area of Science:
- Cellular biology
- Molecular biology
- Cardiovascular research
Background:
- Signaling pathway interactions regulate cellular functions like proliferation.
- The Galpha(s)/cAMP pathway is known to inhibit mitogen-activated protein kinase (MAPK) signaling.
- Previous studies showed cAMP or activated Galpha(s) inhibits vascular smooth muscle cell (VSMC) proliferation in vitro.
Purpose of the Study:
- To investigate if Galpha(s)/cAMP pathway mechanisms regulate VSMC proliferation in vivo.
- To determine the effect of activated Galpha(s) on neointima formation after vascular injury.
- To explore the therapeutic potential of targeting the Galpha(s) pathway for vascular diseases.
Main Methods:
- Inducing VSMC proliferation in rat carotid arteries via balloon injury.
- Administering recombinant adenovirus encoding activated Galpha(s) (alpha(s)*) or beta-galactosidase (control) to injured arteries.
- Assessing phospho-MAPK staining in arterial intima.
- Quantifying neointima formation and vessel dimensions.
Main Results:
- Alpha(s)* treatment decreased phospho-MAPK staining in the intima compared to controls.
- Application of alpha(s)*-encoding adenovirus inhibited neointima formation by 50%.
- No significant changes were observed in total vessel diameter, media, or adventitia.
Conclusions:
- The interaction between Galpha(s) and MAPK pathways regulates VSMC proliferation in vivo.
- Targeted expression of activated Galpha(s) can inhibit neointima formation.
- Activated Galpha(s) holds therapeutic promise for vascular pathologies involving intimal hyperplasia.
