Abstract

We used optical coherence tomography (OCT) to characterize the morphological phenotype of embryonic murine hearts discerning hexamethylene-bis-acetamide-inducible protein 1 (HEXIM1) mutants from their wild-type littermates. At E12.5 and E13.5 murine embryos were excised from the mother, the hearts were removed, and 3D OCT data sets were obtained from each heart in the litter. Next, we segmented the morphological borders to obtain cavity volumes and wall thicknesses. The mutant hearts exhibited increased ventricular chamber volume and decreased compact myocardium wall thickness when compared with their wild-type littermates. Also, the E13.5 HEXIM1 −∕− embryo was distinguished by morphological asymmetry (underdeveloped left side).

© 2007 Optical Society of America

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  1. W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
    [CrossRef] [PubMed]
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    [PubMed]
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    [CrossRef] [PubMed]
  4. H. Deng, Y. Doughman, L. Chaplin, M. Watanabe, and M. M. Montano, "A critical role for HEXIM1 in heart development," FASEB J. 20:A1304-a (2006).
    [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [PubMed]

2006 (4)

2005 (2)

Z. Hu and A. M. Rollins, "Quasi-telecentric optical design of a microscope-compatible OCT scanner," Opt. Express 13, 6407-6415 (2005).
[CrossRef] [PubMed]

B. M. Wittmann, K. Fujinaga, H. Deng, N. Ogba, and M. M. Montano, "The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1," Oncogene 24, 5576-5588 (2005).
[CrossRef] [PubMed]

2003 (2)

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography--principles and applications," Rep. Prog. Phys. 66, 1-239 (2003).
[CrossRef]

B. M. Wittmann, N. Wang, and M. M. Montano, "Identification of a novel inhibitor of breast cell growth that is down-regulated by estrogens and decreased in breast tumors," Cancer Res. 63, 5151-5158 (2003).
[PubMed]

2002 (1)

T. M. Yelbuz, M. A. Choma, L. Thrane, M. L. Kirby, and J. A. Izatt, "Optical coherence tomography a new high-resolution imaging technology to study cardiac development in chick embryos," Circulation 106, 2771-2774 (2002).
[CrossRef] [PubMed]

2000 (1)

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

1999 (1)

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

1998 (1)

1997 (1)

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomograpy," Proc. Natl. Acad. Sci. U.S.A. 94, 4256-4261 (1997).
[CrossRef] [PubMed]

1996 (1)

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Abraham, D.

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

Aharinejad, S.

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

Blumer, R.

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

Boppart, M. D.

Boppart, S. A.

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, "Three-dimensional optical coherence tomography of the embryonic murine cardiovascular system," J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

J. J. Pasquesi, S. C. Schlachter, M. D. Boppart, E. Chaney, S. J. Kaufman, and S. A. Boppart, "In vivo detection of exercise-induced ultrastructural changes in genetically-altered murine skeletal muscle using polarization-sensitive optical coherence tomography," Opt. Express 14, 1547-1556 (2006).
[CrossRef] [PubMed]

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomograpy," Proc. Natl. Acad. Sci. U.S.A. 94, 4256-4261 (1997).
[CrossRef] [PubMed]

Bouma, B. E.

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomograpy," Proc. Natl. Acad. Sci. U.S.A. 94, 4256-4261 (1997).
[CrossRef] [PubMed]

Brezinski, M. E.

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomograpy," Proc. Natl. Acad. Sci. U.S.A. 94, 4256-4261 (1997).
[CrossRef] [PubMed]

Brusselmans, K.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Carmeliet, P.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Chaney, E.

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Chaplin, L.

H. Deng, Y. Doughman, L. Chaplin, M. Watanabe, and M. M. Montano, "A critical role for HEXIM1 in heart development," FASEB J. 20:A1304-a (2006).
[PubMed]

H. Deng, Y. Doughman, L. Chaplin, C. Padro, A. Koch, N. Wang, N. Ward, M. Watanabe, and M. M. Montano are preparing a paper to be called "Disruption of HEXIM1 gene: effects on heart and vascular development."

Choma, M. A.

T. M. Yelbuz, M. A. Choma, L. Thrane, M. L. Kirby, and J. A. Izatt, "Optical coherence tomography a new high-resolution imaging technology to study cardiac development in chick embryos," Circulation 106, 2771-2774 (2002).
[CrossRef] [PubMed]

Collen, D.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Cornelissen, I.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Daly, M. J.

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

D'Amore, P. A.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Damron-Boles, D.

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

Deng, H.

H. Deng, Y. Doughman, L. Chaplin, M. Watanabe, and M. M. Montano, "A critical role for HEXIM1 in heart development," FASEB J. 20:A1304-a (2006).
[PubMed]

B. M. Wittmann, K. Fujinaga, H. Deng, N. Ogba, and M. M. Montano, "The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1," Oncogene 24, 5576-5588 (2005).
[CrossRef] [PubMed]

H. Deng, Y. Doughman, L. Chaplin, C. Padro, A. Koch, N. Wang, N. Ward, M. Watanabe, and M. M. Montano are preparing a paper to be called "Disruption of HEXIM1 gene: effects on heart and vascular development."

Dewerchin, M.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Dietrich, W. F.

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

Doughman, Y.

H. Deng, Y. Doughman, L. Chaplin, M. Watanabe, and M. M. Montano, "A critical role for HEXIM1 in heart development," FASEB J. 20:A1304-a (2006).
[PubMed]

H. Deng, Y. Doughman, L. Chaplin, C. Padro, A. Koch, N. Wang, N. Ward, M. Watanabe, and M. M. Montano are preparing a paper to be called "Disruption of HEXIM1 gene: effects on heart and vascular development."

Dredge, R.

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

Drexler, W.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography--principles and applications," Rep. Prog. Phys. 66, 1-239 (2003).
[CrossRef]

Efimov, I. R.

Ehler, E.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Fercher, A. F.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography--principles and applications," Rep. Prog. Phys. 66, 1-239 (2003).
[CrossRef]

Flameng, W.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Fujimoto, J. G.

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomograpy," Proc. Natl. Acad. Sci. U.S.A. 94, 4256-4261 (1997).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Fujinaga, K.

B. M. Wittmann, K. Fujinaga, H. Deng, N. Ogba, and M. M. Montano, "The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1," Oncogene 24, 5576-5588 (2005).
[CrossRef] [PubMed]

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Hitzenberger, C. K.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography--principles and applications," Rep. Prog. Phys. 66, 1-239 (2003).
[CrossRef]

Hofbauer, R.

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

Hu, Z.

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Husain, Z.

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

Ingalls, K. A.

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

Izatt, J.

Izatt, J. A.

T. M. Yelbuz, M. A. Choma, L. Thrane, M. L. Kirby, and J. A. Izatt, "Optical coherence tomography a new high-resolution imaging technology to study cardiac development in chick embryos," Circulation 106, 2771-2774 (2002).
[CrossRef] [PubMed]

Jenkins, M. W.

Kakkar, V. V.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Kaufman, M. H.

M. H. Kaufman, The Atlas of Mouse Development (Academic, 1998).

Kaufman, S. J.

Kirby, M. L.

T. M. Yelbuz, M. A. Choma, L. Thrane, M. L. Kirby, and J. A. Izatt, "Optical coherence tomography a new high-resolution imaging technology to study cardiac development in chick embryos," Circulation 106, 2771-2774 (2002).
[CrossRef] [PubMed]

Koch, A.

H. Deng, Y. Doughman, L. Chaplin, C. Padro, A. Koch, N. Wang, N. Ward, M. Watanabe, and M. M. Montano are preparing a paper to be called "Disruption of HEXIM1 gene: effects on heart and vascular development."

Kocher, A.

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

Kulkarni, M.

Lasser, T.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography--principles and applications," Rep. Prog. Phys. 66, 1-239 (2003).
[CrossRef]

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Luo, W.

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, "Three-dimensional optical coherence tomography of the embryonic murine cardiovascular system," J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

Lupu, E.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Marks, D. L.

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, "Three-dimensional optical coherence tomography of the embryonic murine cardiovascular system," J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

Mattot, V.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Merchant, M. A.

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

Miksovsky, A.

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

Miller, J.

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

Montano, M. M.

H. Deng, Y. Doughman, L. Chaplin, M. Watanabe, and M. M. Montano, "A critical role for HEXIM1 in heart development," FASEB J. 20:A1304-a (2006).
[PubMed]

B. M. Wittmann, K. Fujinaga, H. Deng, N. Ogba, and M. M. Montano, "The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1," Oncogene 24, 5576-5588 (2005).
[CrossRef] [PubMed]

B. M. Wittmann, N. Wang, and M. M. Montano, "Identification of a novel inhibitor of breast cell growth that is down-regulated by estrogens and decreased in breast tumors," Cancer Res. 63, 5151-5158 (2003).
[PubMed]

H. Deng, Y. Doughman, L. Chaplin, C. Padro, A. Koch, N. Wang, N. Ward, M. Watanabe, and M. M. Montano are preparing a paper to be called "Disruption of HEXIM1 gene: effects on heart and vascular development."

Moons, L.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Nagy, A.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Ng, Y. S.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Nikolski, V. P.

Nuyens, D.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

O'Connor, T. J.

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

Ogba, N.

B. M. Wittmann, K. Fujinaga, H. Deng, N. Ogba, and M. M. Montano, "The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1," Oncogene 24, 5576-5588 (2005).
[CrossRef] [PubMed]

Padro, C.

H. Deng, Y. Doughman, L. Chaplin, C. Padro, A. Koch, N. Wang, N. Ward, M. Watanabe, and M. M. Montano are preparing a paper to be called "Disruption of HEXIM1 gene: effects on heart and vascular development."

Pasquesi, J. J.

Paulus, P.

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

Perriard, J. C.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Ralston, T. S.

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, "Three-dimensional optical coherence tomography of the embryonic murine cardiovascular system," J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

Rollins, A. M.

Rothenberg, F.

Roy, D.

Schafer, R.

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

Schlachter, S. C.

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Shima, D. T.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Southern, J. F.

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomograpy," Proc. Natl. Acad. Sci. U.S.A. 94, 4256-4261 (1997).
[CrossRef] [PubMed]

Stalmans, I.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Steen, R.

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Tearney, G. J.

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomograpy," Proc. Natl. Acad. Sci. U.S.A. 94, 4256-4261 (1997).
[CrossRef] [PubMed]

Theilmeier, G.

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Thrane, L.

T. M. Yelbuz, M. A. Choma, L. Thrane, M. L. Kirby, and J. A. Izatt, "Optical coherence tomography a new high-resolution imaging technology to study cardiac development in chick embryos," Circulation 106, 2771-2774 (2002).
[CrossRef] [PubMed]

Traxler, H.

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

Ung-Arunyawee, R.

Wang, N.

B. M. Wittmann, N. Wang, and M. M. Montano, "Identification of a novel inhibitor of breast cell growth that is down-regulated by estrogens and decreased in breast tumors," Cancer Res. 63, 5151-5158 (2003).
[PubMed]

H. Deng, Y. Doughman, L. Chaplin, C. Padro, A. Koch, N. Wang, N. Ward, M. Watanabe, and M. M. Montano are preparing a paper to be called "Disruption of HEXIM1 gene: effects on heart and vascular development."

Ward, N.

H. Deng, Y. Doughman, L. Chaplin, C. Padro, A. Koch, N. Wang, N. Ward, M. Watanabe, and M. M. Montano are preparing a paper to be called "Disruption of HEXIM1 gene: effects on heart and vascular development."

Watanabe, M.

H. Deng, Y. Doughman, L. Chaplin, M. Watanabe, and M. M. Montano, "A critical role for HEXIM1 in heart development," FASEB J. 20:A1304-a (2006).
[PubMed]

M. W. Jenkins, F. Rothenberg, D. Roy, Z. Hu, V. P. Nikolski, M. Watanabe, D. L. Wilson, I. R. Efimov, and A. M. Rollins, "4D embryonic cardiography using gated optical coherence tomography," Opt. Express 14, 736-748 (2006).
[CrossRef] [PubMed]

H. Deng, Y. Doughman, L. Chaplin, C. Padro, A. Koch, N. Wang, N. Ward, M. Watanabe, and M. M. Montano are preparing a paper to be called "Disruption of HEXIM1 gene: effects on heart and vascular development."

Wilson, D. L.

Wittmann, B. M.

B. M. Wittmann, K. Fujinaga, H. Deng, N. Ogba, and M. M. Montano, "The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1," Oncogene 24, 5576-5588 (2005).
[CrossRef] [PubMed]

B. M. Wittmann, N. Wang, and M. M. Montano, "Identification of a novel inhibitor of breast cell growth that is down-regulated by estrogens and decreased in breast tumors," Cancer Res. 63, 5151-5158 (2003).
[PubMed]

Yazdanfar, S.

Yelbuz, T. M.

T. M. Yelbuz, M. A. Choma, L. Thrane, M. L. Kirby, and J. A. Izatt, "Optical coherence tomography a new high-resolution imaging technology to study cardiac development in chick embryos," Circulation 106, 2771-2774 (2002).
[CrossRef] [PubMed]

Cancer Res. (1)

B. M. Wittmann, N. Wang, and M. M. Montano, "Identification of a novel inhibitor of breast cell growth that is down-regulated by estrogens and decreased in breast tumors," Cancer Res. 63, 5151-5158 (2003).
[PubMed]

Circ. Res. (1)

D. Abraham, R. Hofbauer, R. Schafer, R. Blumer, P. Paulus, A. Miksovsky, H. Traxler, A. Kocher, and S. Aharinejad, "Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy," Circ. Res. 87, 644-647 (2000).
[PubMed]

Circulation (1)

T. M. Yelbuz, M. A. Choma, L. Thrane, M. L. Kirby, and J. A. Izatt, "Optical coherence tomography a new high-resolution imaging technology to study cardiac development in chick embryos," Circulation 106, 2771-2774 (2002).
[CrossRef] [PubMed]

FASEB J. (1)

H. Deng, Y. Doughman, L. Chaplin, M. Watanabe, and M. M. Montano, "A critical role for HEXIM1 in heart development," FASEB J. 20:A1304-a (2006).
[PubMed]

J. Biomed. Opt. (1)

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, "Three-dimensional optical coherence tomography of the embryonic murine cardiovascular system," J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

Nat. Med. (1)

P. Carmeliet, Y. S. Ng, D. Nuyens, G. Theilmeier, K. Brusselmans, I. Cornelissen, E. Ehler, V. V. Kakkar, I. Stalmans, V. Mattot, J. C. Perriard, M. Dewerchin, W. Flameng, A. Nagy, E. Lupu, L. Moons, D. Collen, P. A. D'Amore, and D. T. Shima, "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188," Nat. Med. 5, 495-502 (1999).
[CrossRef] [PubMed]

Nature (1)

W. F. Dietrich, J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, and T. J. O'Connor, "A comprehensive genetic map of the mouse genome," Nature 380, 149-152 (1996).
[CrossRef] [PubMed]

Oncogene (1)

B. M. Wittmann, K. Fujinaga, H. Deng, N. Ogba, and M. M. Montano, "The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1," Oncogene 24, 5576-5588 (2005).
[CrossRef] [PubMed]

Opt. Express (4)

Proc. Natl. Acad. Sci. U.S.A. (1)

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomograpy," Proc. Natl. Acad. Sci. U.S.A. 94, 4256-4261 (1997).
[CrossRef] [PubMed]

Rep. Prog. Phys. (1)

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography--principles and applications," Rep. Prog. Phys. 66, 1-239 (2003).
[CrossRef]

Science (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Other (2)

H. Deng, Y. Doughman, L. Chaplin, C. Padro, A. Koch, N. Wang, N. Ward, M. Watanabe, and M. M. Montano are preparing a paper to be called "Disruption of HEXIM1 gene: effects on heart and vascular development."

M. H. Kaufman, The Atlas of Mouse Development (Academic, 1998).

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Figures (4)

Fig. 1
Fig. 1

E13.5 wild-type embryonic murine heart: 3D surface rendering reconstructed from (a) OCT data, (b) video microscope image, and (c) 2D en face OCT image. RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle; and IVS, interventricular septum.

Fig. 2
Fig. 2

Illustration of morphological measurement techniques. (a) Atrial wall thickness measurements were made using radial lines. Radial lines are drawn outward from a center point in the atrial cavity and the length of the intersection with the wall is computed. (b) For nonspherical or elliptical atria, wall thickness was measured manually. (c) Ventricular volumes were measured using thresholding and voxel counting. (d) Compact myocardial thickness was measured by manually determining the distance from outer trabecular spaces to the outer surface of the ventricles. RA, right atrium; RV, right ventricle; LA, left atrium; and LV, left ventricle.

Fig. 3
Fig. 3

E12.5 HEXIM1 mutant heart versus its wild-type littermate. (a) Two-dimensional en face OCT image of the HEXIM1 wild-type heart. (b) Two-dimensional en face OCT image of the HEXIM1 mutant murine heart. Enlarged ventricular cavities and thinned compact myocardium are evident in the 2D image. (c) Three-dimensional volume composite image reconstructed from OCT data of the wild-type heart. (d) Three-dimensional volume composite image reconstructed from OCT data of the mutant heart. Mutant heart appears to be smaller and younger developmentally. RA, right atrium; RV, right ventricle; LV, left ventricle; LA, left atrium; and IVS, interventricular septum.

Fig. 4
Fig. 4

E13.5 HEXIM1 mutant heart versus its wild-type littermate. (a) Two-dimensional en face OCT image of the HEXIM1 wild-type heart. One can clearly see the interventricular septum, which is absent in the transgenic heart. (b) Two-dimensional en face OCT image of the HEXIM1 mutant murine heart. Left atrium is much smaller than in the wild type and the left ventricle is not fully formed (no cavity), while the cavity in the right ventricle is enlarged. (c) Video microscope image of the wild-type heart prior to OCT imaging. (d) Video microscope image of the transgenic heart prior to OCT imaging. Note the absence of blood in the left ventricle (no cavity). (e) Three-dimensional surface rendering reconstructed from OCT data of the wild-type heart. (f) Three-dimensional surface rendering reconstructed from OCT data of the mutant heart. RA, right atrium; RV, right ventricle; LV, left ventricle; LA, left atrium; and IVS, interventricular septum.

Tables (2)

Tables Icon

Table 1 Physiological Parameters of the Atria a

Tables Icon

Table 2 Physiological Parameters of the Ventricle a

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