Characterization of microcirculatory endothelial functions in a D-Galactose-induced aging model.

BACKGROUND

Microcirculation health is critical to human health, and aging is an important factor affecting microcirculation health. Although D-Galactose has been widely used in aging research models, there is a lack of relevant studies on D-Galactose simulating microcirculatory aging. Here, we explored microcirculatory endothelial function in D-Galactose-induced aging mice.

METHODS

Intraperitoneal injection of 150 mg/(kg·d) of D-Galactose was given to cause senescence in mice. Aging was evaluated by SA-β-gal (senescence-associated β-galactosidase) staining. The auricular skin and hepatic microcirculation of mice were observed and detected by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) and microcirculation apparatus. The aging of microcirculation was analyzed from oxidative stress, endothelial impairment, inflammation, microvascular morphology and hemodynamics.

RESULTS

In aging mice, percentage of SA-β-gal positive area, oxidative stress products reactive oxygen species (ROS) and nitric oxide (NO), endothelial impairment marker syndecan-1 (SDC-1), stromal cell derived factor-1 (SDF-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the senescence-associated secretory phenotype (SASP) were all up-regulated. The tortuosity of microvessels increased in aging mice, the linear density did not change significantly, but the total length of narrow microvessels (TLNMV) increased and wide microvessels (TLWMV) decreased, speculate that vasomotor dysfunction may be present. Hemodynamically, both perfusion and velocity of blood flow were reduced in senescent mice, presumably due to endothelial dysfunction.

CONCLUSION

Microcirculatory endothelial dysfunction is induced by D-Galactose, leading to microcirculatory aging. In vivo, this is manifested by elevated levels of oxidative stress, impaired endothelial glycocalyx (eGC), and a greater production of chemokines and adhesive molecules. These changes cause vasomotor dysfunction and remodeling, ultimately leading to hemodynamic impairment.