The Research Group on Inflammation and vascular remodelling of the IIB Sant Pau, led by Dr. Cristina Rodríguez, has recently published the article “Lysyl oxidase (LOX) limits VSMC proliferation and neointimal thickening through its extracellular Enzymatic activity” in the journal Scientific Reports. The work delves into the mechanisms involved in the ability of lysyl oxidase (LOX) to limit vascular remodeling and proliferation of smooth muscle cells (CMLV) in the vascular wall.
The work, published in the journal Scientific Reports delves into the mechanisms involved in the ability of lysyl oxidase (LOX) to limit vascular remodeling and proliferation of CMLVs characteristic of the restenosis process and has been directed by Dr. Cristina Rodríguez and Dr. José Martínez González (CSIC), researchers at CIBERCV.
LOX is a key enzyme in the synthesis and maturation of the extracellular matrix that contributes to the control of vascular remodelling through the regulation of cell proliferation, calcification of the matrix and the production of oxidative stress. This enzyme, a priori, has a fundamentally extracellular location, although it also has intracellular forms. In addition and surprisingly, some of the cellular responses regulated by LOX do not depend on its enzymatic activity. However, the biological function and possible contribution to the control of LOX vascular remodeling had not been analyzed. The results of the study, obtained through strategies of pharmacological inhibition and overexpression in human vascular cells and studies in transgenic mice that overexpress LOX, indicate that the extracellular and enzymatically active form of LOX is responsible for the antiproliferative effect of this enzyme in CMLV and suggests that pharmacological control of the activity of this enzyme could limit vascular remodelling in pathological processes such as restenosis.
In developed countries, cardiovascular diseases continue to be the main cause of morbidity and mortality. Revascularization by percutaneous transluminal coronary angioplasty (PTCA) is a widely used therapeutic measure in the treatment of coronary artery disease, although its greatest limitation is restenosis, which is a complex process in which, in response to the damage produced by PTCA, a vascular remodeling is produced characterized by the proliferation of CMLV and the production of components of the extracellular matrix. This response leads to obstruction of the vessel’s light, again compromising the irrigation of the heart muscle. This is a significant problem, both clinically and economically, which still has a high incidence, despite advances in the development of releasing stents and antiproliferative drugs. Therefore, it is essential to study this process in order to identify new strategies that prevent the appearance of restenosis and limit its development.
