Microvasculature remodeling in the mouse lower gut during inflammaging

Area of Science:

• Immunology
• Gastroenterology
• Vascular Biology

Background:

• Inflammaging, a chronic, low-grade systemic inflammation, is linked to aging.
• Age-associated decline in gastrointestinal function may be related to inflammaging, but direct evidence is limited.

Purpose of the Study:

• To investigate the impact of inflammaging on microvessel integrity in the aging mouse intestine.
• To elucidate the molecular mechanisms underlying age-related changes in intestinal microvasculature.

Main Methods:

• Analysis of microvessel structures, pericytes, and VE-cadherin in aging mouse intestines.
• Assessment of angiopoietin-2 and TNF-α levels.
• Identification of macrophage populations (CD206+) involved in the inflammatory process.

Main Results:

• Aging mice showed progressive loss of pericytes and VE-cadherin in intestinal microvessels, resulting in vascular leakage.
• Increased angiopoietin-2 expression in microvascular endothelial cells was observed.
• TNF-α from M2-like macrophages was identified as the inducer of angiopoietin-2 and subsequent vascular leakage.

Conclusions:

• Chronic antigenic stimulation in the intestine contributes to inflammaging by accumulating M2-like macrophages.
• These macrophages produce TNF-α, which up-regulates angiopoietin-2, causing vascular leakage.
• This vascular leakage facilitates immune cell recruitment into the aging intestine, perpetuating chronic inflammation.