PostDoc Fellowship: Aruna Poduri Role of Cell Specific-AT1aR Activation in Angil-Induced SMC Hyperplasia and Hypertrophy in Ascending Aorta

Grants and Contracts Details


Infusion of AngII stimulates diverse effects on smooth muscle cells (SMCs) via angiotensin II type 1a receptor (AT1aR). The Sponsor’s laboratory has demonstrated that AngII promotes medial thickening throughout the aorta. However, the underlying mechanism of the thickening differs with hyperplasia being the cause in ascending aorta and hypertrophy in rest of the aorta. The basis for the heterogeneous response of aortic media to AngII is unclear. Potential mechanisms may include heterogenous responses of SMCs to AngII in the ascending aorta versus the rest of the aortic tree. They may also include indirect effects of AngII acting on endothelial cells (ECs) to influence SMC function. The regional differences may also be a combination of these mechanisms. The contribution of specific cell types to AngII-induced SMC medial hyperplasia and hypertrophy via AT1aR has not been determined. The Sponsor’s laboratory has also demonstrated that AngII-induced SMC hyperplasia occurs via inhibitor of differentiation (Id3) dependent manner. Id3 is a helix-loop-helix transcription factor and enhances SMC proliferation via production of reactive oxygen species in response to AngII. Sources of Id3 remains unclear. Previous studies and preliminary data demonstrated that ECs express Id3 protein. It has not been determined whether AngII-induced hyperplasia is due to Id3 expression in ECs or SMCs. Understanding the role of specific cell types in vascular remodeling may identify a basis to develop a target that reduces the onset of progression of several vascular diseases. Based on my preliminary studies and above background information, the proposal tests the central hypothesis that AngII promotes medial hyperplasia in the ascending aorta through an indirect endothelial-dependent mechanism while medial hypertrophy in the rest of the aorta is a direct effect on SMC. To test this hypothesis, the following aims are proposed: Aim 1: Determine the effects of either EC or SMC-specific depletion of AT1aR on AngII-induced aortic medial hyperplasia and hypertrophy. Aim 2: Determine whether the effects of Id3 deficiency on AngII-induced hyperplasia are due to the presence of this protein in ECs or SMCs.
Effective start/end date7/1/106/30/12


  • American Heart Association Great Rivers Affiliate: $88,000.00


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