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Statins normalize vascular lysyl oxidase down-regulation
22 July 2009
Catalan Institute of Cardiovascular Sciences
Statins are lipid-lowering drugs widely used in the treatment of vascular diseases. Clinical and experimental evidence indicate that statins improve endothelial function by both cholesterol lowering-dependent and -independent mechanisms.
Recent research published in Cardiovascular Research by CSIC-ICCC’s vascular biology group has shown that pharmacological concentrations of statins (atorvastatin and simvastatin) prevented the inhibition of LOX expression and enzymatic activity caused by tumour necrosis factor alpha (TNFalpha) in endothelial cells in culture. Furthermore, statins were also able to counteract the decrease in LOX expression produced by atherogenic concentrations of LDL and to partially prevent the increase in endothelial permeability caused by these lipoproteins. In addition, in vivo, in the porcine model the research team observed that statins normalize vascular LOX expression decreased by hypercholesterolemia.
The Dr. Rodriguez-Sinovas’ team had previously shown that endothelial dysfunction induced by atherogenic risk factors and proinflammatory cytokines is associated with the down-regulation of LOX, a key enzyme in extracellular matrix maturation and vascular integrity maintenance.
Dr. Rodriguez-Sinovas affirms that "our results suggest that normalization of vascular LOX expression could be a new mechanism associated with the improvement of endothelial function produced by these drugs through mechanisms beyond the reduction of plasma cholesterol levels”
The CSIC-ICCC research group has shown that an increase in LOX gene transcription is the main mechanism for the normalization of LOX expression caused by statins. These drugs can interfere with signalling pathways that modulate gene expression and vascular function. "These results provide the first evidence that pharmacological control of LOX by statins might contribute to the cardiovascular risk reduction and the vascular beneficial actions achieved with this therapy", concludes Dr. Rodriguez-Sinovas.