This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 25/8/1603    most recent 01.ATV.0000171994.89106.cav1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schiekofer, S. Articles by Walsh, K. Search for Related Content PubMed PubMed Citation Articles by Schiekofer, S. Articles by Walsh, K. Related Collections Obesity Type 2 diabetes Angiogenesis Gene expression

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1603.)
© 2005 American Heart Association, Inc.

Vascular Biology

Impaired Revascularization in a Mouse Model of Type 2 Diabetes Is Associated With Dysregulation of a Complex Angiogenic-Regulatory Network

Stephan Schiekofer; Gennaro Galasso; Kaori Sato; Benjamin J. Kraus; Kenneth Walsh

From the Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Massachusetts.

Correspondence to Dr Kenneth Walsh, PhD, Molecular Cardiology/Whitaker Cardiovascular Institute Boston University School of Medicine, 715 Albany St, W611 Boston, MA 02118. E-mail kxwalsh{at}bu.edu

Objective— Diabetes is a risk factor for the development of cardiovascular diseases associated with impaired angiogenesis or increased endothelial cell apoptosis.

Methods and Results— Here it is shown that angiogenic repair of ischemic hindlimbs was impaired in Lepr^db/db mice, a leptin receptor–deficient model of diabetes, compared with wild-type (WT) C57BL/6 mice, as evaluated by laser Doppler flow and capillary density analyses. To identify molecular targets associated with this disease process, hindlimb cDNA expression profiles were created from adductor muscle of Lepr^db/db and WT mice before and after hindlimb ischemia using Affymetrix GeneChip Mouse Expression Set microarrays. The expression patterns of numerous angiogenesis-related proteins were altered in Lepr^db/db versus WT mice after ischemic injury. These transcripts included neuropilin-1, vascular endothelial growth factor-A, placental growth factor, elastin, and matrix metalloproteinases implicated in blood vessel growth and maintenance of vessel wall integrity.

Conclusion— These data illustrate that impaired ischemia-induced neovascularization in type 2 diabetes is associated with the dysregulation of a complex angiogenesis-regulatory network.

Angiogenic repair of ischemic hindlimbs was impaired in diabetic Lepr^db/db and WT mice as evaluated by laser Doppler measurements. cDNA expression profiles were created from adductor muscle of Lepr^db/db and WT mice before and after hindlimb ischemia illustrating the dysregulation of a complex angiogenesis-regulatory network in diabetic mice.

Key Words: diabetes • ischemia • angiogenesis • microarrays

This article has been cited by other articles:

				J. Siebert, M. Reiwer-Gostomska, Z. Babinska, J. Mysliwska, A. Mysliwski, E. Skopinska-Rozewska, E. Sommer, and P. Skopinski Low Serum Angiogenin Concentrations in Patients With Type 2 Diabetes Diabetes Care, December 1, 2007; 30(12): 3086 - 3087. [Full Text] [PDF]

				J. W. Ji, F. Mac Gabhann, and A. S. Popel Skeletal muscle VEGF gradients in peripheral arterial disease: simulations of rest and exercise Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3740 - H3749. [Abstract] [Full Text] [PDF]

				R. Kivela, M. Silvennoinen, M. Lehti, H. Kainulainen, and V. Vihko Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2573 - H2579. [Abstract] [Full Text] [PDF]

				S. M. Vartanian and R. Sarkar Therapeutic Angiogenesis Vascular and Endovascular Surgery, July 1, 2007; 41(3): 173 - 185. [Abstract] [PDF]

				S. J. Miller, L. E. Norton, M. P. Murphy, M. C. Dalsing, and J. L. Unthank The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2523 - H2531. [Abstract] [Full Text] [PDF]

				Y. Li, S. Hazarika, D. Xie, A. M. Pippen, C. D. Kontos, and B. H. Annex In Mice With Type 2 Diabetes, a Vascular Endothelial Growth Factor (VEGF)-Activating Transcription Factor Modulates VEGF Signaling and Induces Therapeutic Angiogenesis After Hindlimb Ischemia Diabetes, March 1, 2007; 56(3): 656 - 665. [Abstract] [Full Text] [PDF]

				S. Yakar, N. P. Nunez, P. Pennisi, P. Brodt, H. Sun, L. Fallavollita, H. Zhao, L. Scavo, R. Novosyadlyy, N. Kurshan, et al. Increased Tumor Growth in Mice with Diet-Induced Obesity: Impact of Ovarian Hormones Endocrinology, December 1, 2006; 147(12): 5826 - 5834. [Abstract] [Full Text] [PDF]

				S. Schiekofer, I. Shiojima, K. Sato, G. Galasso, Y. Oshima, and K. Walsh Microarray analysis of Akt1 activation in transgenic mouse hearts reveals transcript expression profiles associated with compensatory hypertrophy and failure Physiol Genomics, October 11, 2006; 27(2): 156 - 170. [Abstract] [Full Text] [PDF]

				R. Kivela, M. Silvennoinen, A.-M. Touvra, T. M. Lehti, H. Kainulainen, and V. Vihko Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle FASEB J, July 1, 2006; 20(9): 1570 - 1572. [Abstract] [Full Text] [PDF]