Abstract

The hypotheses to be tested in each case have been organized according to the following three Specific Aims.
Specific Aim #1 : To investigate the potential for endothelial cell (EC) mitogens to accelerate re-endothelialization (rET);
Specific Aim #2 : To investigate certain mechanisms by which EC mitogens facilitate rET;
and Specific Aim #3 : To investigate augmented rET using EC precursors isolated from peripheral blood. The studies will be performed in vitro and in vivo. The latter will include a hyperlipidemic rabbit model of double-balloon injury, and, in selected cases, rat and mouse models of single and/or double-balloon injury. Experiments in Specific Aim #1 are expected to define, short of human studies, the potential for EC mitogens to effectively modulate pathologic alteration of the artery wall. Experiments from Specific Aim #2 are expected to elucidate the role of vascular endothelial growth factor (VEGF) as a previously unappreciated endogenous regulatory factor responsible for maintaining and restoring the integrity of the vascular endothelium. Experiments form Specific Aim 3 are considered by the applicant to constitute a """"""""supply side"""""""" strategy that will consider circulating EC precursors as penultimate ECs that may be used in conjunction with EC mitogens to augment rET.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057516-04
Application #
6125828
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1997-01-01
Project End
2000-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
4
Fiscal Year
2000
Total Cost
$294,732
Indirect Cost

  Institution

Name
St. Elizabeth's Medical Center of Boston
Department
Type
DUNS #
073797292
City
Boston
State
MA
Country
United States
Zip Code
01235

  Publications

Morishita, Yoshihiro; Kobayashi, Koichi; Klyachko, Ekaterina et al. (2016) Wnt11 Gene Therapy with Adeno-associated Virus 9 Improves Recovery from Myocardial Infarction by Modulating the Inflammatory Response. Sci Rep 6:21705
Sekiguchi, Haruki; Ii, Masaaki; Jujo, Kentaro et al. (2013) Estradiol promotes neural stem cell differentiation into endothelial lineage and angiogenesis in injured peripheral nerve. Angiogenesis 16:45-58
Masuda, Haruchika; Asahara, Takayuki (2013) Clonogenic assay of endothelial progenitor cells. Trends Cardiovasc Med 23:99-103
Jujo, Kentaro; Ii, Masaaki; Sekiguchi, Haruki et al. (2013) CXC-chemokine receptor 4 antagonist AMD3100 promotes cardiac functional recovery after ischemia/reperfusion injury via endothelial nitric oxide synthase-dependent mechanism. Circulation 127:63-73
Mackie, Alexander R; Klyachko, Ekaterina; Thorne, Tina et al. (2012) Sonic hedgehog-modified human CD34+ cells preserve cardiac function after acute myocardial infarction. Circ Res 111:312-21
Sekiguchi, Haruki; Ii, Masaaki; Jujo, Kentaro et al. (2012) Estradiol triggers sonic-hedgehog-induced angiogenesis during peripheral nerve regeneration by downregulating hedgehog-interacting protein. Lab Invest 92:532-42
Masuda, Haruchika; Iwasaki, Hiroto; Kawamoto, Atsuhiko et al. (2012) Development of serum-free quality and quantity control culture of colony-forming endothelial progenitor cell for vasculogenesis. Stem Cells Transl Med 1:160-71
Losordo, Douglas W; Kibbe, Melina R; Mendelsohn, Farrell et al. (2012) A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia. Circ Cardiovasc Interv 5:821-30
Nishimura, Yukihide; Ii, Masaaki; Qin, Gangjian et al. (2012) CXCR4 antagonist AMD3100 accelerates impaired wound healing in diabetic mice. J Invest Dermatol 132:711-20
Sahoo, Susmita; Klychko, Ekaterina; Thorne, Tina et al. (2011) Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity. Circ Res 109:724-8

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