Abstract

Aberrant growth of blood vessels termed 'angiogenesis'contributes to the pathology of several human diseases ranging from macular degeneration, retinopathy to inflammation and cancer. Recently small RNAs encoded in the genome termed microRNAs have been implicated in the regulation of diverse physiological processes including angiogenesis. We recently profiled microRNAs during activation of endothelial cells and identified microRNA-132 as a critical regulator of p120RasGAP during pathological neovascularization. In this proposal, I will characterize the role of miR-132/p120RasGAP in cell survival during stress responses in the vasculature using in vitro and in vivo angiogenesis models during the mentored phase. Using these models, in the independent phase, I will analyze the contribution of a different microRNA that functions as a negative regulator of cell survival in vascular cells. These studies will elucidate how distinct microRNA programs govern the balance between the pro and anti-angiogenic states in the vasculature during development and disease.

Public Health Relevance

While the role of specific microRNAs (miR) in promoting endothelial activation has been well characterized, it is not clear how miRs regulate endothelial survival and apoptosis. In this proposal, during my K99 phase, I will address the role of angiomiR miR-132 in regulating cell survival in the vasculature. In the independent phase, I will analyze the contribution of a pro-apoptotic miR, miR-34 in mediating cell death in the vasculature and its effects on the Notch signaling pathway.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Career Transition Award (K99)
Project #
1K99HL112962-01
Application #
8279906
Study Section
Special Emphasis Panel (ZHL1-CSR-P (F1))
Program Officer
Scott, Jane
Project Start
2012-06-01
Project End
2014-02-28
Budget Start
2012-06-01
Budget End
2013-02-28
Support Year
1
Fiscal Year
2012
Total Cost
$97,871
Indirect Cost
$7,250

  Institution

Name
University of California San Diego
Department
Pathology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Westenskow, Peter D; Kurihara, Toshihide; Aguilar, Edith et al. (2013) Ras pathway inhibition prevents neovascularization by repressing endothelial cell sprouting. J Clin Invest 123:4900-8
Anand, Sudarshan (2013) A brief primer on microRNAs and their roles in angiogenesis. Vasc Cell 5:2
Anand, Sudarshan; Cheresh, David A (2011) Emerging Role of Micro-RNAs in the Regulation of Angiogenesis. Genes Cancer 2:1134-8
Anand, Sudarshan; Cheresh, David A (2011) MicroRNA-mediated regulation of the angiogenic switch. Curr Opin Hematol 18:171-6