Stylized blood vessel showing the impact of arginase, aging, and obesity.

Could Arginase Be the Key to Slowing Down Aging and Obesity's Effects on Your Arteries?

Jordan Keane in Health & Wellness July 2025 • 4 min read.

"New research explores how arginase, an enzyme, impacts blood vessel health in obese individuals and how aging modulates this process."

Obesity is a widespread health issue linked to significant illness and mortality, largely due to its detrimental effects on the cardiovascular system. Obesity hastens the progression of atherosclerosis, triggering physiological changes that can be detected even in young adults. These changes closely resemble those typically seen with aging, underscoring the importance of understanding how obesity affects our bodies over time.

One of the earliest signs of vascular dysfunction in obese individuals is a reduction in nitric oxide (NO) availability. NO is crucial for maintaining vascular homeostasis and facilitating remodeling, a process that helps blood vessels adapt to changing conditions. The enzyme eNOS (endothelial NO synthase) is vital in producing NO, converting L-arginine into NO and L-citrulline. Reduced availability of L-arginine, the substrate eNOS uses, can impair NO production, leading to endothelial dysfunction.

Arginase, a manganese metalloenzyme, breaks down L-arginine into urea and L-ornithine. It exists in two isoforms, arginase I and II, both found in various tissues, including the cardiovascular system. Elevated arginase concentrations can cause eNOS uncoupling, reducing NO production and impairing endothelial function. Additionally, arginase may contribute to vascular remodeling, promoting inflammation and senescence in endothelial cells and supporting the proliferation of smooth muscle cells and collagen synthesis. Since both reduced NO availability and accelerated vascular aging are key factors in obesity-related vascular diseases, researchers are exploring the potential role of arginase I and II.

How Does Arginase Affect Blood Vessels in Obesity?

Stylized blood vessel showing the impact of arginase, aging, and obesity.

A study published in Arteriosclerosis, Thrombosis, and Vascular Biology investigated the role of arginase in small arteries of obese patients, examining its relationship with aging and microvascular remodeling. Researchers collected small artery samples from subcutaneous fat biopsies of both obese and non-obese participants. They then assessed endothelium-dependent vasodilation, a measure of blood vessel flexibility, using acetylcholine. These tests were conducted under various conditions, including the presence of L-NAME (an eNOS inhibitor), N(w)-hydroxy-nor-L-arginine (an arginase inhibitor), and gp91ds-tat (an NADPH oxidase inhibitor).

The study evaluated several factors to assess vascular health, including:

Media-lumen ratio: A measure of blood vessel wall thickness.
Vascular wall fibrosis: The amount of fibrous tissue in the vessel wall.
Vascular superoxide anions and NO production: Indicators of oxidative stress and NO availability.
Arginase expression: The amount of arginase in the vessel wall.

The results indicated that obese and older participants had lower vascular NO levels, higher media-lumen ratios, increased wall fibrosis, elevated intravascular superoxide, and a reduced inhibitory effect of L-NAME on acetylcholine. These findings suggest impaired endothelial function and increased oxidative stress in these groups. However, when N(ω)-hydroxy-nor-L-arginine, an arginase inhibitor, was introduced, the acetylcholine-induced vasodilation was partially restored, particularly in younger obese subjects. This effect was abolished by L-NAME, confirming that the restoration was NO-dependent. Further, gp91ds-tat, an NADPH oxidase inhibitor, improved the vasodilatory response to N(ω)-hydroxy-nor-L-arginine in older obese subjects. The study also found higher levels of superoxide anions and arginase I/II in the vascular walls of obese participants.

What Does This Mean for You?

This research highlights that arginase contributes to microvascular endothelial dysfunction in obesity, but its impact is reduced by aging due to higher levels of vascular oxidative stress. Obesity is also associated with accelerated microvascular remodeling, with the extent of remodeling linked to the amount of arginase in the vascular wall. These findings suggest that targeting arginase might be a valuable strategy for maintaining vascular health, especially in younger obese individuals.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1161/atvbaha.118.311074, Alternate LINK

Title: Aging Modulates The Influence Of Arginase On Endothelial Dysfunction In Obesity

Subject: Cardiology and Cardiovascular Medicine

Journal: Arteriosclerosis, Thrombosis, and Vascular Biology

Publisher: Ovid Technologies (Wolters Kluwer Health)

Authors: Stefano Masi, Rocchina Colucci, Emiliano Duranti, Monica Nannipieri, Marco Anselmino, Chiara Ippolito, Erika Tirotta, Georgios Georgiopoulos, Francesca Garelli, Anna Nericcio, Cristina Segnani, Nunzia Bernardini, Corrado Blandizzi, Stefano Taddei, Agostino Virdis

Published: 2018-10-01

Everything You Need To Know

What is arginase, and how does it affect blood vessel health?

Arginase is an enzyme that breaks down L-arginine into urea and L-ornithine. It exists in two forms, arginase I and arginase II, both present in various tissues, including the cardiovascular system. Elevated arginase levels can lead to eNOS uncoupling, reducing nitric oxide production and impairing how well the endothelium functions. Arginase may also contribute to vascular remodeling by promoting inflammation and senescence in endothelial cells and supporting the proliferation of smooth muscle cells and collagen synthesis. Therefore, controlling arginase activity is seen as an avenue to improve blood vessel health.

Why is nitric oxide (NO) important for vascular health?

Nitric oxide (NO) is crucial for maintaining vascular homeostasis and facilitating remodeling, which helps blood vessels adapt to changing conditions. The enzyme eNOS (endothelial NO synthase) produces NO by converting L-arginine into NO and L-citrulline. Obesity-related vascular issues, such as reduced NO availability and accelerated vascular aging, underscore the significance of NO in vascular health. Maintaining adequate NO levels is essential for ensuring proper vascular function and overall cardiovascular health. If nitric oxide levels decrease, the blood vessels become unhealthy.

How does obesity affect microvascular remodeling, and what role does arginase play in this process?

The study found that obesity is associated with accelerated microvascular remodeling, and this remodeling is linked to the amount of arginase present in the vascular wall. Vascular remodeling involves changes in the structure of blood vessels, including thickening of the vessel wall (media-lumen ratio) and increased fibrosis. The research also found elevated intravascular superoxide, indicating increased oxidative stress. These changes can lead to impaired endothelial function and reduced blood vessel flexibility. Arginase plays a role in promoting these changes, which emphasizes the importance of managing its activity to maintain vascular health.

How can arginase inhibitors improve vascular function, and what other factors are involved?

An arginase inhibitor, such as N(ω)-hydroxy-nor-L-arginine, can partially restore acetylcholine-induced vasodilation, especially in younger obese subjects. This restoration is NO-dependent, meaning that it relies on the availability of nitric oxide. Additionally, NADPH oxidase inhibitors, like gp91ds-tat, can improve the vasodilatory response to arginase inhibitors in older obese subjects. These findings suggest that by inhibiting arginase, vascular function can be improved, particularly when combined with strategies to reduce oxidative stress. It can also help improve vasodilation.

What is the role of L-arginine in vascular health, and how does arginase affect its availability?

L-arginine is the substrate that eNOS uses to produce nitric oxide (NO). Arginase breaks down L-arginine into urea and L-ornithine, reducing the amount of L-arginine available for NO production. This can impair NO production, leading to endothelial dysfunction. Therefore, maintaining an adequate supply of L-arginine is crucial for ensuring sufficient NO production and healthy vascular function. Because it provides the necessary ingredients to create nitric oxide, an important ingredient for vasodilation.