Faculty Collaboration Database

Coordinate expression of the insulin-like growth factor system after microembolisation in porcine heart. Cardiovasc Res 1997 Feb;33(2):324-31

Date

02/01/1997

Pubmed ID

9074696

DOI

10.1016/s0008-6363(96)00236-2

Scopus ID

2-s2.0-0031028605 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

OBJECTIVES: Coronary microembolisation in the pig heart induces angiogenesis in a model of sterile inflammation due to focal necrosis. We have recently shown in this model that insulin-like growth factor I (IGF-I) is involved in inflammation-linked angiogenic processes due to its enhanced transcription after 72 h of ischaemia by infiltrating monocytes in areas of microsphere-induced focal necrosis where capillary sprouting could be detected. To obtain further insights into this process we studied by means of Northern blot analysis and in situ hybridisation the gene expression of other members of the IGF family, i.e. the six IGF binding proteins (IGFBPs), the insulin receptor, and the type I IGF receptor.

METHODS: Myocardial injury was induced by injection of 25 microns non-radioactive microspheres into the left circumflex artery (LCx) in pigs that were killed after 3-24, 72, or 168 h of microembolisation. Tissue was collected from a non-ischaemic control area and the LCx region of the same heart for further analysis.

RESULTS: We found decreased IGFBP-5 (2.7-fold; P < 0.02) mRNA concentrations after 72 h of microembolisation in ischaemic tissue versus control tissue from the same heart, preceded by a 1.9-fold elevated level of IGFBP-3 mRNA at 3-24 h (P < 0.05). IGFBP-6 was increased in ischaemic tissue at all time points studied. In situ hybridisation identified myocytes as the main producers of IGFBP-3 and IGFBP-6 mRNA. The mRNA levels of IGFBP-2, IGFBP-4, the insulin receptor, and the type I IGF receptor were constitutively expressed but did not change after microembolisation. Neither in heart nor in other organs studied transcripts of IGFBP-1 could be detected. Furthermore, we demonstrated that mRNA of the other components of the IGF system was expressed in almost all porcine organs except liver.

CONCLUSION: These results indicate a coordinate gene expression of the IGF system in microembolised porcine myocardium, compatible with a role of IGF-I, IGFBP-3, IGFBP-5, and IGFBP-6 in inflammation-linked angiogenesis and/or repair processes.

Author List

Kluge A, Zimmermann R, Weihrauch D, Mohri M, Sack S, Schaper J, Schaper W

Author

Dorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Northern
Embolism
Gene Expression
In Situ Hybridization
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor Binding Protein 6
Insulin-Like Growth Factor Binding Proteins
Male
Microspheres
Myocardium
RNA, Messenger
Receptor, IGF Type 1
Receptor, Insulin
Somatomedins
Swine