Lysyl oxidase (LOX) in vascular remodelling
Por:
Orriols, M, Guadall, A, Galan, M, Marti-Pamies, I, Varona, S, Rodriguez-Calvo, R, Briones, AM, Navarro, MA, de Diego, A, Osada, J, Martinez-Gonzalez, J, Rodriguez, C
Publicada:
1 oct 2014
Resumen:
Lysyl oxidase (LOX) is an extracellular matrix-modifying enzyme that seems to play a critical role in vascular remodelling. However, the lack of viable LOX-deficient animal models has been an obstacle to deep in LOX biology. In this study we have developed a transgenic mouse model that over-expresses LOX in vascular smooth muscle cells (VSMC) to clarify whether LOX could regulate VSMC phenotype and vascular remodelling. The SM22 alpha proximal promoter drove the expression of a transgene containing the human LOX cDNA. Two stable transgenic lines, phenotypically indistinguishable, were generated by conventional methods (TgLOX).Transgene expression followed the expected SMC-specific pattern. In TgLOX mice, real-time PCR and immunohistochemistry evidenced a strong expression of LOX in the media from aorta and carotid arteries, coincident with a higher proportion of mature collagen. VSMC isolated from TgLOX mice expressed high levels of LOX pro-enzyme, which was properly secreted and processed into mature and bioactive LOX. Interestingly, cell proliferation was significantly reduced in cells from TgLOX mice. Transgenic VSMC also exhibited low levels of Myh10 (marker of SMC phenotypic switching), PCNA (marker of cell proliferation) and MCP-1, and a weak activation of Akt and ERK1/2 in response to mitogenic stimuli. Accordingly,; neointimal thickening induced by carotid artery ligation was attenuated in TgLOX mice that also displayed a reduction in PCNA and MCP-1 immunostaining. Our results give evidence that LOX plays a critical role in vascular remodelling.We have developed a new animal model to study the role of LOX in vascular biology.
Filiaciones:
Orriols, M:
CSIC ICCC Inst Invest Biomed St Pau IIB St Pau, Ctr Invest Cardiovasc, Barcelona, Spain
Guadall, A:
CSIC ICCC Inst Invest Biomed St Pau IIB St Pau, Ctr Invest Cardiovasc, Barcelona, Spain
Galan, M:
CSIC ICCC Inst Invest Biomed St Pau IIB St Pau, Ctr Invest Cardiovasc, Barcelona, Spain
Marti-Pamies, I:
CSIC ICCC Inst Invest Biomed St Pau IIB St Pau, Ctr Invest Cardiovasc, Barcelona, Spain
Varona, S:
CSIC ICCC Inst Invest Biomed St Pau IIB St Pau, Ctr Invest Cardiovasc, Barcelona, Spain
Rodriguez-Calvo, R:
CSIC ICCC Inst Invest Biomed St Pau IIB St Pau, Ctr Invest Cardiovasc, Barcelona, Spain
Briones, AM:
Univ Autonoma Madrid, Fac Med, Dept Farmacol, Inst Invest Hosp Univ La Paz IdiPAZ, Madrid, Spain
Navarro, MA:
Univ Zaragoza, Fac Vet, CIBEROBN, Zaragoza, Spain
de Diego, A:
Inst Aragonas Ciencias Salud, Unidad Transganesis, Zaragoza, Spain
Osada, J:
Univ Zaragoza, Fac Vet, CIBEROBN, Zaragoza, Spain
Martinez-Gonzalez, J:
CSIC ICCC Inst Invest Biomed St Pau IIB St Pau, Ctr Invest Cardiovasc, Barcelona, Spain
Rodriguez, C:
CSIC ICCC Inst Invest Biomed St Pau IIB St Pau, Ctr Invest Cardiovasc, Barcelona, Spain
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