A large body of in vitro studies has helped to elucidate intracellular pathways that lead to mitogenic signaling in vascular smooth muscle (VSM) cells. However, a limitation of these studies is that they fail to test the in vivo physiological significance especially because VSM proliferation, in the forms of intimal hyperplasia and restenosis, is an important clinical problem. The recent advent of adenoviral gene transfer technology has made possible to test the in vivo effects of specific molecular modulations of intracellular signal transduction pathways on physiological responses. For example, in VSM, adenoviruses can be delivered to the vessel wall to determine a gene/protein's role in proliferative responses to vascular injury. This technology, once standardized and rendered safe for human applications, will be the basis of gene therapy and molecular medicine. Several exemplary applications have now been generated in the vascular system, including the use of an adenovirus containing the carboxyl-terminus of the beta-adrenergic receptor kinase (beta ARKct), which binds to the beta gamma-subunits of activated heterotrimeric G proteins (G beta gamma), to study the in vivo role of G beta gamma in VSM intimal hyperplasia after vascular injury that leads to restenosis.

In vivo adenoviral-mediated gene transfer of the beta ARKct to study the role of G beta gamma in arterial restenosis.

Guido Iaccarino;
2004

Abstract

A large body of in vitro studies has helped to elucidate intracellular pathways that lead to mitogenic signaling in vascular smooth muscle (VSM) cells. However, a limitation of these studies is that they fail to test the in vivo physiological significance especially because VSM proliferation, in the forms of intimal hyperplasia and restenosis, is an important clinical problem. The recent advent of adenoviral gene transfer technology has made possible to test the in vivo effects of specific molecular modulations of intracellular signal transduction pathways on physiological responses. For example, in VSM, adenoviruses can be delivered to the vessel wall to determine a gene/protein's role in proliferative responses to vascular injury. This technology, once standardized and rendered safe for human applications, will be the basis of gene therapy and molecular medicine. Several exemplary applications have now been generated in the vascular system, including the use of an adenovirus containing the carboxyl-terminus of the beta-adrenergic receptor kinase (beta ARKct), which binds to the beta gamma-subunits of activated heterotrimeric G proteins (G beta gamma), to study the in vivo role of G beta gamma in VSM intimal hyperplasia after vascular injury that leads to restenosis.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/339809
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