Mitochondrial Fusion Plays A Crucial Role In The Effect Of Renin-Angiotensin Signal Inhibition On Retarding Arterial Senescence And Atherosclerosis

Introduction: Mitochondria are dynamic organelles that undergo fusion and fission. Renin-angiotensin signal (RAS) accelerates arterial senescence and develops arteriosclerosis. This study aims to clarify whether mitochondrial dynamics is involved in the effect of RAS inhibition on arterial senescence and atherosclerosis. Methods u0026 Results: We used C57BL6, apolipoprotein E knockout (ApoE KO) and double KO mice (DKO) of angiotensin II type Ia receptor KO and ApoE KO. Dynamin-related protein 1 (Drp1), which mediates mitochondrial fission, was activated with phosphorylation at serine 616 and mitochondrial fusion assessed by electron microscopy decreased in the artery of ApoE KO compared to age-matched C57BL6. Mfn1/Mfn2, Opa1 and Fis1, which also modulate mitochondrial dynamics, did not differ between them. The degree of arterial senescence and atherosclerosis are greater in ApoE KO than in C57BL6 assessed by senescence associated beta galactosidase and oil red o staining and immunoblot of p-eNOS/eNOS, PAI-1, ...