Highlights
- •Gpihbp1-/- promotes atherosclerosis (AS) and plaques instability in Ldlr-/- mice.
- •Diabetes accelerates AS and elicits coronary AS and aortic remodeling.
- •Gpihbp1 deficiency aggravates AS by increasing oxidative stress and inflammation.
Abstract
Background and aims
Glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1)
plays a crucial role in triglyceride hydrolysis, and GPIHBP1 deficiency leads to severe
hypertriglyceridemia (HTG). Gpihbp1 knockout (GKO) mice develop mild lesions in the aortic root at the age of 11 months.
Herein, we investigated the effect of Gpihbp1 deficiency on atherosclerosis (AS) under diabetic conditions.
Methods
For experiment 1, diabetes was induced in GKO and wild-type (WT) mice by injection
of streptozotocin at 3 months of age and lasted for 4 months. For experiment 2, diabetes
was induced in Gpihbp1/low-density lipoprotein receptor (Ldlr) double-knockout (GLDKO) mice, Ldlr knockout (LKO) mice were used as controls. The experiment was continued for 3 or
5 months. Plasma glucose and lipid levels were measured, and atherosclerotic lesions
were analyzed at 3 and 5 months during the experiment.
Results
No atherosclerotic lesions were detected in the aorta in GKO mice after 4 months of
diabetes. Compared with LKO mice, GLDKO mice manifested enhanced aortic atherosclerotic
lesions, decreased plaque stability, and increased oxidative stress and inflammation
in plaques at 3 and 5 months after diabetes. Atherosclerotic lesions in the coronary
artery and dilated remodeling in the aortic root were also found in GLDKO diabetic
mice.
Conclusions
Gpihbp1 deficiency accelerates the development of AS in the aorta, and the instability of
plaques in LKO mice and diabetes promotes these pathologic processes with coronary
AS. These findings were probably associated with HTG caused by Gpihbp1 deficiency and with increased oxidative stress and inflammation in the atherosclerotic
lesions.
Graphical abstract
Graphical Abstract
Keywords
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Article Info
Publication History
Published online: January 28, 2019
Accepted:
January 15,
2019
Received in revised form:
December 29,
2018
Received:
June 14,
2018
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
