Effect of dalteparin on atherosclerotic lesion formation in apolipoprotein E-deficient mice

Area of Science:

• Cardiovascular Research
• Pharmacology
• Biochemistry

Background:

• Atherosclerosis is a chronic inflammatory disease characterized by plaque buildup in arteries.
• Oxidized low-density lipoprotein receptor 1 (LOX-1) plays a critical role in the development and progression of atherosclerotic lesions.
• Dalteparin, a low molecular weight heparin, has potential anti-inflammatory and anti-atherosclerotic properties.

Purpose of the Study:

• To investigate the efficacy of prolonged dalteparin treatment in inhibiting atherosclerotic plaque progression.
• To determine the effect of dalteparin on the expression of LOX-1 in apolipoprotein E-deficient (apo E(-/-)) mice.
• To assess the persistence of dalteparin's effects after treatment discontinuation.

Main Methods:

• Apo E(-/-) mice were randomly assigned to control (no dalteparin) or dalteparin treatment groups (100 and 200 U/kg/day).
• Aortic plaque volume was assessed using hematoxylin and eosin staining.
• LOX-1 expression was evaluated at the protein level (immunohistochemistry, Western blotting) and mRNA level (RT-PCR).

Main Results:

• Dalteparin treatment significantly decreased aortic plaque volume in apo E(-/-) mice.
• Dalteparin administration led to reduced aortic LOX-1 protein expression.
• The observed reduction in plaque volume and LOX-1 expression persisted for 4 weeks after dalteparin treatment was stopped.

Conclusions:

• Prolonged dalteparin treatment effectively inhibits atherosclerotic plaque progression in apo E(-/-) mice.
• Dalteparin exerts its anti-atherosclerotic effects, at least in part, by downregulating LOX-1 protein expression.
• The inhibitory effects of dalteparin on atherosclerosis are sustained even after the cessation of treatment.