Regulation of vascular smooth muscle cell phenotype by changes in phospholipase C gamma expression: relationship to the pathogenesis of vascular disease. . (360G-Wellcome-081980_Z_07_Z)

£124,288

The molecular mechanisms regulating vascular smooth muscle (VSM) cell proliferation during vascular disease are not well understood. These mechanisms regulate selective gene expression leading to changes in protein expression necessary for proliferation. A previous study, and further preliminary evidence, has indicated that phospholipase C gamma (PLCg) expression is regulated dependent upon VSM phenotype both in vitro and in vivo. This study will examine the hypothesis that these changes in PL Cg expression can act as a molecular switch and regulate VSM phenotype towards either proliferation or differentiation. It is proposed that this mechanism occurs via the selective activation of the Ca2+-dependent phosphatase, calcineurin and subsequent regulation of key transcription factors. Experiments will use overexpression/knockdown of PLCg in cultured VSM cells to determine how changes in growth factor-stimulated pathways correlate with altered PLCg expression. These pathways will inc lude Ca2+ signalling, transcription factor activation/interaction and ultimately regulation of gene expression and growth. Further experiments will test the validity of this hypothesis using an in vivo vascular injury model. This study will uncover an important mechanism in regulating VSM phenotype and will further demonstrate that this may be involved in the development of vascular disease.

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Grant Details

Amount Awarded 124288
Applicant Surname Nixon
Approval Committee Physiological Sciences Funding Committee
Award Date 2007-02-22T00:00:00+00:00
Financial Year 2006/07
Grant Programme: Title Project Grant
Internal ID 081980/Z/07/Z
Lead Applicant Prof Graeme Nixon
Other Applicant(s) Dr Simon Kennedy, Prof Roger Wadsworth
Partnership Value 124288
Planned Dates: End Date 2009-07-31T00:00:00+00:00
Planned Dates: Start Date 2007-08-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland