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An Issue of Culture: Comparison of Vascular Endothelial and Smooth Muscle Cell Coculture and the Intact Vessel State
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An Issue of Culture: Comparison of Vascular Endothelial and Smooth Muscle Cell Coculture and the Intact Vessel State

Shaun L Sandow
Journal of Vascular Research, Vol.45(Supplement 1), p.86
International Symposium on Resistance Arteries (ISRA), 9th (Hamilton Island, Australia, 17-Feb-2008–21-Feb-2008)
2008
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Abstract

Medical and Health Sciences cell culture
Introduction: Cell culture has been integral for elucidating many fundamental aspects of the signal transduction mechanisms associated with cellular and tissue function. In this regard, it is critical that observations from culture be considered with caution in terms of their relevance to what occurs in intact tissue. For example, studies of cocultured mouse aortic endothelial and smooth muscle cells have been useful in elucidating mechanisms that may be involved in vascular endothelialsmooth muscle (myoendothelial) signaling. However, what does this model represent? Methods, Results & Discussion: Serial section ultrastructural studies show that myoendothelial gap junctions (MEGJs) are absent in intact adult mouse and rat aorta and that they are present in aorta from 14d male mice and in adult ApoE knockout animals (n=4, each from a different animal; the developmental observation being similar to the situation in the rat saphenous/femoral artery.1,2) In cocultured mouse aortic endothelial and smooth muscle cells, MEGJs occur in relatively high prevalence.3 The Cx43 make-up of such junctions contrasts with the presence of Cxs37 and 40 at MEGJs in resistance vessels;4 potentially reflecting differences in the fundamental functional heterogeneity between conduit and resistance vessels, or perhaps between intact vascular tissue and the (co)cultured state. In this regard, it is unknown whether the Cx nature of MEGJs in coculture reflects that of intact developmental and diseased aortic tissue. Of interest, in many vascular beds the vasodilator endothelium-derived hyperpolarization (EDH) mechanism is dependent on MEGJs,4-6 with correlative and concomitant modification in development, ageing and disease. Indeed, the presence and absence of MEGJs in aorta shows apparent correspondence with EDH-dependent vasodilation; this mechanism being present in rat aorta of juvenile7 and disease models (hypercholesterolemic, diabetic and hypertensive and with altered oestrogen levels), but absent in healthy adult aorta.8-14 Conclusion: For use as a model of vascular MEGJ coupling, cocultured mouse aortic endothelial and smooth muscle contacts may reflect the state of the juvenile or diseased aorta, but it does not reflect the state in the normal adult aorta. It is interesting that cocultured mouse aortic endothelial and smooth muscle cells can form MEGJs and further studies are required to determine if the cocultured mouse aortic model3 reflects a state which occurs in intact tissue.

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