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Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues
Published on: June 3, 2019
Upregulation of aortic adhesion molecules during aging
Yani Zou1, Sik Yoon, Kyung Jin Jung
1College of Pharmacy, Pusan National University, Gumjung-gu, Busan 609-735, Korea.
Summary
Aging increases aortic adhesion molecules (AMs), such as P-selectin and vascular cell adhesion molecule-1 (VCAM-1), in rats. This is linked to oxidative stress and the nuclear factor-kappaB pathway, contributing to inflammation.
Area of Science:
- Cardiovascular biology
- Aging research
- Molecular biology
Background:
- Adhesion molecules (AMs) play a critical role in leukocyte trafficking and inflammation.
- Aging is associated with increased cardiovascular risk and inflammatory processes.
- Oxidative stress and the nuclear factor-kappaB (NF-κB) pathway are implicated in age-related vascular dysfunction.
Purpose of the Study:
- To investigate the age-related changes in aortic expression of P-selectin and vascular adhesion molecule-1 (VCAM-1).
- To explore the role of oxidative stress and the NF-κB pathway in mediating these age-related changes.
- To assess the impact of calorie restriction on these molecular markers of aging.
Main Methods:
- Comparison of aortic P-selectin and VCAM-1 expression in young (6-month) and old (24-month) Fischer 344 rats under ad libitum (AL) feeding and calorie restriction.
- Measurement of myeloperoxidase (MPO) levels to assess leukocyte infiltration.
- Assessment of oxidative stress markers, including lipid peroxides.
- Analysis of the nuclear factor-kappaB-inducing kinase (NIK)/IkappaB kinase (IKK)/Inhibitor of kappaB (IkappaB) pathway activation.
- In vitro studies using cultured endothelial cells exposed to oxidative stimuli.
Main Results:
- Old AL rats exhibited significantly increased aortic P-selectin and VCAM-1 levels compared to young rats.
- Elevated AMs in old AL rats correlated with increased MPO levels, indicating greater leukocyte infiltration.
- Aging was associated with heightened oxidative stress, including increased lipid peroxides.
- Activation of the NIK/IKK/IkappaB/NF-κB pathway was more pronounced in the aortas of old AL rats.
- Oxidative stress in cultured endothelial cells induced overexpression and promoter activity of P-selectin and VCAM-1.
Conclusions:
- Aortic expression of adhesion molecules is upregulated with age in Fischer 344 rats.
- This age-related upregulation is closely associated with increased oxidative stress and activation of the NIK/IKK/IkappaB/NF-κB pathway.
- These findings highlight a molecular mechanism linking aging, oxidative stress, inflammation, and vascular changes.
