Diabetes mellitus frequently causes endothelial damage, dramatically accelerating the progression of vascular diseases.However, the molecular mechanisms remain to be defined.Specific complement molecules have been demonstrated to play an important role in vascular injury.Previous research in our laboratory showed that the aortic endothelium of diabetic mice contained high levels of C1qa, which increased with the development of cardiovascular diseases.To investigate the effect of a dietary inhibitor of C1qa, 1,2,3,4,6-O-pentagalloylglucose (PGG), on diabetic vascular endothelial repair, we established a streptozocin (STZ) diabetic mice model.Results showed that exogenous C1qa stimulation significantly increased vascular endothelial reactive oxygen species (ROS) levels while decreasing aortic endothelium-dependent diastolic function.Likewise, in diabetic mice, high vascular endothelial C1qa levels were associated with excessive ROS synthesis and significantly reduced endothelium-dependent diastole in aortic segments.Nevertheless, three weeks of PGG gavage in diabetic mice considerably reduced aortic endothelial C1qa expression, decreased blood glucose to 15.36 mmol/L, a 52.41% reduction in ROS production, and an increased rate in vascular endothelial diastolic from 47.06% to 68.41%.Simultaneously, PGG downregulated the expression of the NADPH oxidase pathway (NOX2/NOX4), indicating that it inhibited the essential pathway of ROS generation.Thus, vascular endothelial damage from oxidative stress got a substantial attenuation.Hence, PGG-targeted inhibition of C1qa is beneficial for repairing aortic endothelial dysfunction in diabetic mice.
ZHANG Ankun
,
LI Zicheng
,
CHEN Jiani
,
HE Dongxu
. Mechanism of pentagalloylglucose targeted complement molecule C1qa for repairing endothelial damage in aorta of diabetic mice[J]. Food and Fermentation Industries, 2024
, 50(17)
: 66
-74
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DOI: 10.13995/j.cnki.11-1802/ts.037237
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