Expression of insulin receptor (IR) A and B isoforms, IGF-IR, and IR/IGF-IR hybrid receptors in vascular smooth muscle cells and their role in cell migration in atherosclerosis.
Cardiovasc Diabetol
; 15(1): 161, 2016 12 01.
Article
in En
| MEDLINE
| ID: mdl-27905925
ABSTRACT
BACKGROUND:
Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic process. In a previous work, we demonstrated that the insulin receptor isoform A (IRA) and its association with the insulin-like growth factor-I receptor (IGF-IR) confer a proliferative advantage to VSMCs. However, the role of IR and IGF-IR in VSMC migration remains poorly understood.METHODS:
Wound healing assays were performed in VSMCs bearing IR (IRLoxP+/+ VSMCs), or not (IR-/- VSMCs), expressing IRA (IRA VSMCs) or expressing IRB (IRB VSMCs). To study the role of IR isoforms and IGF-IR in experimental atherosclerosis, we used ApoE-/- mice at 8, 12, 18 and 24 weeks of age. Finally, we analyzed the mRNA expression of total IR, IRB isoform, IGF-IR and IGFs by qRT-PCR in the medial layer of human aortas.RESULTS:
IGF-I strongly induced migration of the four cell lines through IGF-IR. In contrast, insulin and IGF-II only caused a significant increase of IRA VSMC migration which might be favored by the formation of IRA/IGF-IR receptors. Additionally, a specific IGF-IR inhibitor, picropodophyllin, completely abolished insulin- and IGF-II-induced migration in IRB, but not in IRA VSMCs. A significant increase of IRA and IGF-IR, and VSMC migration were observed in fibrous plaques from 24-week-old ApoE-/- mice. Finally, we observed a marked increase of IGF-IR, IGF-I and IGF-II in media from fatty streaks as compared with both healthy aortas and fibrolipidic lesions, favoring the ability of medial VSMCs to migrate into the intima.CONCLUSIONS:
Our data suggest that overexpression of IGF-IR or IRA isoform, as homodimers or as part of IRA/IGF-IR hybrid receptors, confers a stronger migratory capability to VSMCs as might occur in early stages of atherosclerotic process.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptor, Insulin
/
Cell Movement
/
Receptor, IGF Type 1
/
Receptor Cross-Talk
/
Myocytes, Smooth Muscle
/
Atherosclerosis
/
Muscle, Smooth, Vascular
Type of study:
Prognostic_studies
Language:
En
Journal:
Cardiovasc Diabetol
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
/
ENDOCRINOLOGIA
Year:
2016
Document type:
Article
Affiliation country:
Spain