Related Experiment Video
Updated: May 12, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Paradoxical protection from atherosclerosis and thrombosis in a mouse model of sickle cell disease
Hui Wang1, Wei Luo, Jintao Wang
1Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI, USA.
Insights
Sickle cell disease (SCD) paradoxically protects against atherosclerosis and thrombosis in mice. This effect is linked to heme oxygenase-1 (HMOX1) induction, revealing complex vascular event mechanisms in SCD.
Area of Science:
- Cardiovascular Biology
- Hematology
- Pathophysiology
Background:
- Sickle cell disease (SCD) is linked to vascular issues like stroke, but its impact on atherothrombosis remains unclear.
- Understanding SCD's role in atherosclerosis and thrombosis is crucial for managing its vascular complications.
Purpose of the Study:
- To investigate the effect of SCD on the development of atherosclerosis and thrombosis.
- To explore the role of heme oxygenase-1 (HMOX1) in SCD-related vascular changes.
Main Methods:
- Mice with SCD (Hbb(hβs/hβs)) and controls (Hbb(+/+)) were created using bone marrow transplantation into recipient mice.
- Atherosclerosis was assessed in the aortic root, and thrombosis was evaluated using a carotid artery model.
- HMOX1 activity was inhibited using zinc protoporphyrin IX to assess its role.
Main Results:
- SCD mice exhibited anemia, reticulocytosis, and splenomegaly.
- Reduced atherosclerotic lesions and macrophage content, with increased collagen, were observed in SCD mice on an Apoe(-/-) background.
- Thrombosis occurred more slowly in SCD mice compared to controls.
- Inhibition of HMOX1 diminished the protective effects of SCD on atherosclerosis and thrombosis.
Conclusions:
- SCD in mice demonstrates a paradoxical protective effect against atherosclerosis and thrombosis.
- This protective effect is, at least partially, mediated by the induction of HMOX1.
- The findings highlight the intricate nature of vascular pathology in sickle cell disease.
Abstract:
Sickle cell disease (SCD) is associated with vascular complications including premature stroke. The role of atherothrombosis in these vascular complications is unclear. To determine the effect of SCD on atherosclerosis and thrombosis, mice with SCD along with controls were generated by transplantation of bone marrow from mice carrying the homozygous sickle cell mutation (Hbb(hβs/hβs) ) or wild-type mice (Hbb(+/+) ) into C57BL6/J or apolipoprotein E deficient (Apoe(-/-) ) recipient mice. At the time of sacrifice, 23-28 weeks following bone marrow transplantation, anaemia, reticulocytosis, and splenomegaly were present in mice receiving Hbb(hβs/hβs) bone marrow compared with control mice. Analysis of atherosclerosis involving the aortic root revealed reduced atherosclerotic lesion area with reduced macrophage content and increased collagen content in Apoe(-/-) , Hbb(hβs/hβs) mice compared to Apoe(-/-) , Hbb(+/+) mice. In a carotid thrombosis model, the time to thrombosis was prolonged in Hbb(hβs/hβs) mice compared to Hbb(+/+) mice. This apparent protective effect of SCD on atherosclerosis and thrombosis was diminished by inhibition of heme oxygenase-1 (HMOX1) using zinc protoporphyrin IX. We conclude that SCD in mice is paradoxically protective against atherosclerosis and thrombosis, highlighting the complexity of vascular events in SCD. This protective effect is at least partially mediated by induction of HMOX1.