Gucy1a3 and coagulation/atherosclerosis

Gucy1a3 encodes for the alpha 1 subunit of the soluble guanylate cyclase (sGC), where nitric oxide binds to increase the levels of cGMP. Gucy1a3 has been associated to CAD in GWAS studies as well as in family studies.
This gene is involved in the regulation of vasodilation, inhibition of platelet adhesion and aggregation and neurotransmission. Mice lacking Gucy1a3 present a reduction in artery relaxation, an abrogation of agonist-induced platelet aggregation and hypertension.
In this project we aim to backcross the Gucy1a3-KO animals to Ldlr-KO background and induce atherosclerosis after feeding the animals with a standard or high fat diet. Studies are on going to reveal the role of Gucy1a3 in atherosclerosis as well as lipid metabolism.
Results from mice we have been able to identify a reduction in plaque size and in collagen content, a reduction in total cholesterol and Ldl levels and hypertension in the Double-KO animals. Present studies include the final characterization of the atherosclerotic plaque, expression analysis in several tissues, a deeper lipid analysis and the study of macrophages, endothelial and smooth muscle cells.

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