Blood Journal
Leading the way in experimental and clinical research in hematology

NHERF-2 maintains endothelial homeostasis

  1. Resham Bhattacharya1,
  2. Enfeng Wang1,
  3. Shamit K. Dutta1,
  4. Pawan K. Vohra1,
  5. Guangqi E1,
  6. Y. S. Prakash2, and
  7. Debabrata Mukhopadhyay1
  1. Departments of 1Biochemistry and Molecular Biology, and
  2. 2Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN

Abstract

The Na+/H+ exchanger regulatory factor-2 (NHERF-2) is an integral component of almost all endothelial cells (ECs), yet its endothelial function is not known. Here, we found that NHERF-2, is a key regulator of endothelial homeostasis because NHERF-2–silenced ECs proliferate at a much higher rate even in the absence of mitogens such as VEGF compared with control ECs. We further show that the hyperproliferation phenotype of NHERF-2–silenced EC is because of an accelerated cell cycle that is probably caused by a combination of the following factors: increased cytoplasmic calcium, increased expression of c-Myc, increased expression of cyclin D1, and reduced expression of p27. Using an experimental mouse model of human hemangioma, we found that the endothelial neoplasms derived from NHERF-2–silenced cells were much larger in volume than those derived from control cells. Thus, NHERF-2 is a negative regulator of endothelial proliferation and may have important roles in endothelial homeostasis and vascular modeling.

  • Submitted November 21, 2011.
  • Accepted January 26, 2012.
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