Autophagy has vasculoprotective roles, but whether and how it regulates lymphatic endothelial cells (LEC) homeostasis and lymphangiogenesis is unknown. Here, we show that genetic deficiency of autophagy in LEC impairs responses to VEGF-C and injury-driven corneal lymphangiogenesis. Autophagy loss in LEC compromises the expression of main effectors of LEC identity, like VEGFR3, affects mitochondrial dynamics and causes an accumulation of lipid droplets (LDs) in vitro and in vivo. When lipophagy is impaired, mitochondrial ATP production, fatty acid oxidation, acetyl-CoA/CoA ratio and expression of lymphangiogenic PROX1 target genes are dwindled. Enforcing mitochondria fusion by silencing dynamin-related-protein 1 (DRP1) in autophagy-deficient LEC fails to restore LDs turnover and lymphatic gene expression, whereas supplementing the fatty acid precursor acetate rescues VEGFR3 levels and signaling, and lymphangiogenesis in LEC-Atg5−/− mice. Our findings reveal that lipophagy in LEC by supporting FAO, preserves a mitochondrial-PROX1 gene expression circuit that safeguards LEC responsiveness to lymphangiogenic mediators and lymphangiogenesis.

The aim of this study was to validate carotid artery strain assessment in-vivo using ultrasound speckle tracking. The left carotid artery of five sheep was exposed and sonomicrometry crystals were sutured onto the artery wall to obtain reference strain. Ultrasound imaging was performed at baseline and stress, followed by strain estimation using an in-house speckle tracking algorithm tuned for vascular applications. The correlation between estimated and reference strain was r = 0.95 (p < 0.001) and r = 0.87 (p < 0.01) for longitudinal and circumferential strain, respectively. Moreover, acceptable limits of agreement were found in Bland-Altman analysis (longitudinally: -0.15 to 0.42%, circumferentially: -0.54 to 0.50%), which demonstrates the feasibility of estimating carotid artery strain using ultrasound speckle tracking. However, further studies are needed to test the algorithm on human in-vivo data and to investigate its potential to detect subclinical cardiovascular disease and characterize atherosclerotic plaques.

Introduction:Available evidence suggests that the renin–angiotensin–aldosterone (RAA) system is a good target for medical intervention on aortic root dilatation in Marfan syndrome (MFS). The effect of Compound 21 (C21), a nonpeptide angiotensin II type 2 receptor agonist, on aneurysm progression was tested.Methods:Mice with a mutation in fibrillin-1 (Fbn1C1039G/+) and wild-type mice were treated with vehicle, losartan, C21, enalapril, or a combination. Blood pressure, aortic root diameter, and histological slides were evaluated.Results:All groups had a comparable blood pressure. Echographic evaluation of the aortic root diameter revealed a protective effect of angiotensin II type 1 receptor antagonist (losartan) and no effect of C21 treatment. None of the treatments had a beneficial effect on the histological changes in MFS.Discussion:This study confirms that angiotensin II type 1 receptor antagonism (losartan) decreases aortic aneurysm growth in a mouse model of MFS. A nonpeptide angiotensin II type 2 receptor agonist (C21), at the doses studied, was ineffective. Future studies are warranted to further elucidate the exact role of the RAA system in aneurysm formation in MFS and identify alternative targets for intervention.