ORCID Profile
0000-0003-0909-7948
Current Organisation
Virginia Tech
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Publisher: Cold Spring Harbor Laboratory
Date: 05-10-2022
DOI: 10.1101/2022.10.02.510555
Abstract: There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. While some common aetiological mechanisms are known, the role of amyloid beta 42 (Aβ 42 ) in these erse chronic diseases is obscure. Here we show that adipose tissue releases Aβ 42 , which is increased from adipose tissue of obese mice and is associated with higher plasma Aβ 42 . Increasing circulating Aβ 42 levels in non-obese mice had no effect on systemic glucose homeostasis but had obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. These effects on cardiac function were not observed when circulating levels of the closely related Aβ 40 isoform were increased. Administration of an Aβ neutralising antibody prevented obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aβ neutralising antibody administration in established obesity prevented further deterioration of cardiac function. Multi-contrast transcriptomic analyses revealed that Aβ 42 impacted pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aβ 42 inhibited mitochondrial function. These data reveal a role for systemic Aβ 42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Wiley
Date: 14-09-2020
DOI: 10.1111/OBR.13145
Publisher: Cold Spring Harbor Laboratory
Date: 27-08-2023
DOI: 10.1101/2023.08.25.554690
Abstract: Objective: While multiple factors influence coronary artery bypass graft success rates, preserving saphenous vein endothelium during surgery may improve patency. Standard methods of saphenous vein graft preparation in heparinized saline (saline) solutions result in endothelial loss and damage. Here we investigated the impact of preparing saphenous graft vessels in heparinized patient blood (blood) vs saline on cellular health and survival. Methods: Saphenous vein tissues from a total of 23 patients undergoing coronary artery bypass graft surgery were split into 2 treatment groups, 1) standard preparation using saline and 2) preparation using blood. Immediately following surgery, excess tissue was fixed for analysis. Level of endothelial coverage, oxidative stress marker 4-hydroxynonenal (4HNE), and oxidative stress protective marker nuclear factor erythroid 2-related factor 2 (NRF2) expression were evaluated. Results: In saline patient veins, histological analysis revealed a broken or absent luminal layer, suggesting a loss of endothelial cell (EC) coverage. Luminal cell coverage was notably preserved in blood-treated s les. Immunofluorescent staining of endothelial markers vascular endothelial cadherin (VE-cadherin) and endothelial nitric oxide (eNOS) identified a significant improvement in endothelial coverage in the blood group compared to saline. Although in both treatment groups EC expressed 4HNE indicating a similar level of oxidative stress, EC stored in blood solutions expressed higher levels of the protective transcription NRF2. Conclusions: Our data indicate that maintaining and preparing saphenous vein tissues in solutions containing heparinized blood helps preserve the endothelium and promotes vein graft health. This has the potential to improve long-term outcomes in patients.
No related grants have been discovered for Mark Renton.