{"id":13593,"date":"2024-02-01T08:06:39","date_gmt":"2024-02-01T08:06:39","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=13593"},"modified":"2024-02-01T08:19:14","modified_gmt":"2024-02-01T08:19:14","slug":"2024-56-dihete-lactone-epa-l-mediates-hypertensive-microvascular-dilation-by-activating-the-endothelial-gpr-plc-ip3-signaling-pathway","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2024-56-dihete-lactone-epa-l-mediates-hypertensive-microvascular-dilation-by-activating-the-endothelial-gpr-plc-ip3-signaling-pathway\/","title":{"rendered":"2024 &#8211; 5,6-diHETE lactone (EPA-L) mediates hypertensive microvascular dilation by activating the endothelial GPR-PLC-IP3 signaling pathway"},"content":{"rendered":"<p>Endothelial microvascular dysfunction affects multi-organ pathologic processes that contribute to increased\u00a0vascular tone\u00a0and is at the base of impaired metabolic and cardiovascular diseases. The\u00a0vascular dilation\u00a0impaired by\u00a0nitric oxide\u00a0(NO) deficiency in such dysfunctional endothelium is often balanced by endothelial-derived hyperpolarizing factors (EDHFs), which play a critical role in managing\u00a0vascular tone. Our latest research has uncovered a new group of lactone\u00a0oxylipins\u00a0produced in the polyunsaturated fatty acids (PUFAs) CYP450\u00a0epoxygenase\u00a0pathway, significantly affecting\u00a0vascular dilation. The lactone oxylipin, derived from\u00a0arachidonic acid\u00a0(5,6-diHET lactone, AA-L), has been previously shown to facilitate vasodilation dependent on the endothelium in isolated human microvessels. The administration of the lactone oxylipin derived from\u00a0eicosapentaenoic acid\u00a0(5,6-diHETE lactone, EPA-L) to hypertensive rats demonstrated a significant decrease in blood pressure and improvement in the relaxation of microvessels. However, the molecular signaling processes that underlie these observations were not fully understood. The current study delineates the molecular pathways through which EPA-L promotes endothelium-dependent vascular dilation. In microvessels from hypertensive individuals, it was found that EPA-L mediates endothelium-dependent vasodilation while the\u00a0signaling pathway\u00a0was not dependent on NO.\u00a0In vitro studies\u00a0on human endothelial cells showed that the hyperpolarization mediated by EPA-L relies on G-protein-coupled receptor (GPR)-phospholipase C (PLC)-IP3 signaling that further activates calcium-dependent\u00a0potassium flux. The pathway was confirmed using a range of inhibitors and cells overexpressing GPR40, where a specific antagonist reduced the calcium levels and outward currents induced by EPA-L. The downstream AKT and endothelial NO synthase (eNOS) phosphorylations were non-significant. These findings show that the GPR-PLC-IP3 pathway is a key mediator in the EPA-L-triggered vasodilation of arterioles. Therefore, EPA-L is identified as a significant lactone-based PUFA metabolite that contributes to endothelial and vascular health.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45],"resource_type":[75],"application_areas":[53,76],"therapeutic_areas":[143],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-13593","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","resource_type-publication","application_areas-assay-development-and-validation","application_areas-drug-discovery","therapeutic_areas-assay-development-and-validation"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/13593","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=13593"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=13593"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=13593"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=13593"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=13593"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=13593"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=13593"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=13593"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=13593"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}