Brigham Research Institute Poster Session Site logo-1
Search
Close this search box.

Ming Tao, MD

Pronouns

Job Title

Investigator

Academic Rank

Instructor

Department

Surgery

Authors

Ming Tao, Peter Kip, Thijs Sluiter, Michael MacArthur, Sarah Mitchell, Margreet R de Vries, Masanori Aikawa, and C. Keith Ozaki

Principal Investigator

C. Keith Ozaki MD

Research Category: Cardiovascular, Diabetes, and Metabolic Disorders

Tags

Dietary Methionine Restriction Attenuates Vein Graft Disease in Diet Induced Obesity Mice

Scientific Abstract

Objective: Obesity is an independent risk factor for cardiovascular disease and revascularization failure. Dietary methionine restriction (MetR), as a novel interventional modality, improves perivascular adipose tissue (PVAT) metabolic fitness and reduces surgical stress in preclinical models. We hypothesized that one-week of pre-operative MetR attenuates vein graft disease.

Methods: Male 12-week-old diet induced obesity (DIO) mice were fed a control diet (60% fat) for 3 weeks, followed by 1 week of MetR (60% fat/0.05% methionine) prior to surgery. 20 mice (n=10) underwent unilateral carotid interposition allografting via a cuff technique (donor mice from the same diet/genetic background, vein cava PVAT attached). All mice were returned to the control diet post-surgery. The grafts were harvested at day 28 for analyses.

Results: MetR led to approximately 17.9% body weight loss. MetR significantly reduced intima area, intima/(media+adventitia) area ratios and improved the remodeling index(p<0.05). Furthermore, short-term MetR significantly increased macrophage M2/M1 ratios in the graft wall(p<0.05).

Conclusions: MetR intervention prior to surgery significantly reduces intimal hyperplasia in DIO mice and is associated with increased M2 macrophage populations. It stands as a simple, translatable strategy for increasing host resistance to surgical trauma and improving vein graft durability.

Lay Abstract

Objective: Obesity is an independent risk factor for cardiovascular disease and revascularization failure. Dietary methionine restriction (MetR), as a novel interventional modality, improves perivascular adipose tissue (PVAT) metabolic fitness and reduces surgical stress in preclinical models. We hypothesized that one-week of pre-operative MetR attenuates vein graft disease.

Methods: Male 12-week-old diet induced obesity (DIO) mice were fed a control diet (60% fat) for 3 weeks, followed by 1 week of MetR (60% fat/0.05% methionine) prior to surgery. 20 mice (n=10) underwent unilateral carotid interposition allografting via a cuff technique (donor mice from the same diet/genetic background, vein cava PVAT attached). All mice were returned to the control diet post-surgery. The grafts were harvested at day 28 for analyses.

Results: MetR led to approximately 17.9% body weight loss. MetR significantly reduced intima area, intima/(media+adventitia) area ratios and improved the remodeling index(p<0.05). Furthermore, short-term MetR significantly increased macrophage M2/M1 ratios in the graft wall(p<0.05).

Conclusions: MetR intervention prior to surgery significantly reduces intimal hyperplasia in DIO mice and is associated with increased M2 macrophage populations. It stands as a simple, translatable strategy for increasing host resistance to surgical trauma and improving vein graft durability.

Clinical Implications

This study leverages a simple nutritional manipulation strategy to prime adipose metabolism in DIO animal before surgery to reduce surgical stress and improve surgical outcomes. It can be easily translated into clinical practice to improve patient care and enhance vascular conduit durability.