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Antiproliferative effect of UTP on human arterial and venous smooth muscle cells
P J White1, R Kumari, K E Porter
1Cell Signalling Laboratory, Department of Biological Sciences, De Montfort University, Leicester LE1 9BH.
Abstract:
We have investigated the hypothesis that responses associated with proliferation are regulated by extracellular nucleotides such as ATP and UTP in cultured human vascular smooth muscle cells (VSMC) derived from internal mammary artery (IMA) and saphenous vein (SV). Platelet-derived growth factor (PDGF), ATP, and UTP each generated an increase in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in both IMA- and SV-derived cells in the absence of detectable inositol 1,4,5-trisphosphate production. ATP alone had no effect on [(3)H]thymidine incorporation into DNA, but with a submaximal concentration of PDGF it raised [(3)H]thymidine incorporation in SV- but not IMA-derived cells. UTP alone also was without effect on [(3)H]thymidine incorporation or cell number. However, in both SV- and IMA-derived cells, UTP reduced the PDGF-stimulated [(3)H]thymidine response and PDGF-stimulated cell proliferation. This cannot be explained by an inhibitory effect on the p42/p44 mitogen-activated protein kinase (MAPK) cascade, since this response to PDGF was not attenuated by UTP. We conclude that, in human VSMC of both arterial and venous origin, UTP acts as an anti-proliferative regulator.
Insights
Extracellular nucleotides like UTP regulate vascular smooth muscle cell proliferation. UTP inhibits platelet-derived growth factor-stimulated proliferation in human vascular smooth muscle cells, acting as an anti-proliferative agent.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Extracellular nucleotides, including adenosine triphosphate (ATP) and uridine triphosphate (UTP), play diverse roles in cellular signaling.
- Vascular smooth muscle cells (VSMC) are crucial for regulating blood vessel tone and structure.
- Understanding the regulation of VSMC proliferation is vital for cardiovascular health.
Purpose of the Study:
- To investigate the role of extracellular nucleotides (ATP and UTP) in regulating proliferation of human vascular smooth muscle cells (VSMC).
- To determine if ATP and UTP influence cell proliferation stimulated by platelet-derived growth factor (PDGF).
Main Methods:
- Cultured human VSMC from internal mammary artery (IMA) and saphenous vein (SV) were used.
- Measurements included cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and [(3)H]thymidine incorporation into DNA.
- Cell proliferation and mitogen-activated protein kinase (MAPK) cascade activation were assessed.
Main Results:
- ATP and UTP increased [Ca(2+)](i) in both IMA- and SV-derived VSMC.
- ATP enhanced PDGF-stimulated [(3)H]thymidine incorporation in SV-derived cells only.
- UTP inhibited PDGF-stimulated [(3)H]thymidine incorporation and cell proliferation in both IMA- and SV-derived VSMC, independent of MAPK signaling.
Conclusions:
- UTP acts as an anti-proliferative regulator in human VSMC of both arterial and venous origin.
- Extracellular nucleotides differentially modulate VSMC proliferation responses.
- UTP's anti-proliferative effect is not mediated through the p42/p44 MAPK cascade.