Related Experiment Video
Updated: Feb 16, 2026
Ultrasound Based Assessment of Coronary Artery Flow and Coronary Flow Reserve Using the Pressure Overload Model in Mice
Published on: April 13, 2015
Widespread Coronary Dysfunction in the Absence of HDL Receptor SR-B1 in an Ischemic Cardiomyopathy Mouse Model
James T Pearson1,2,3,4, Misa Yoshimoto5,6, Yi Ching Chen7
1Monash Biomedical Imaging Facility, Melbourne, Victoria, Australia. jpearson@ncvc.go.jp.
Insights
Scavenger receptor B1 (SR-B1) deficiency impairs nitric oxide (NO)-mediated coronary vasodilation, contributing to occlusive coronary artery disease and ischemic cardiomyopathy progression.
Area of Science:
- Cardiovascular Biology
- Lipid Metabolism
- Vascular Physiology
Background:
- Reduced high-density lipoprotein (HDL) clearance via scavenger receptor class B1 (SR-B1) is implicated in coronary artery disease.
- The contribution of microvascular dysfunction to ischemic cardiomyopathy remains unclear.
Purpose of the Study:
- To investigate coronary vascular dysfunction in mice with SR-B1 deficiency after high-fat diet exposure.
- To determine the role of nitric oxide (NO) and endothelium-derived hyperpolarization factors (EDHF) in this dysfunction.
Main Methods:
- Utilized SR-B1 deficient and heterozygous mice with hypomorphic ApoE lipoprotein.
- Assessed coronary dilator function in vivo using synchrotron microangiography.
- Administered acetylcholine, sodium nitroprusside, L-NAME, and sodium meclofenamate to evaluate vascular responses.
Main Results:
- Partially occlusive stenoses were observed exclusively in SR-B1 deficient mice.
- SR-B1 deficiency abolished artery-arteriole dilation to acetylcholine and sodium nitroprusside.
- EDHF-mediated dilation remained intact, except at occlusions, indicating NO-mediated impairment.
Conclusions:
- SR-B1 deficiency impairs NO-mediated dilation in coronary conductance and microvessels.
- Loss of NO-mediated vasodilation contributes to atherothrombotic progression in ischemic cardiomyopathy.
- EDHF and prostanoids play roles in global perfusion, but NO loss is critical.
Abstract:
Reduced clearance of lipoproteins by HDL scavenger receptor class B1 (SR-B1) plays an important role in occlusive coronary artery disease. However, it is not clear how much microvascular dysfunction contributes to ischemic cardiomyopathy. Our aim was to determine the distribution of vascular dysfunction in vivo in the coronary circulation of male mice after brief exposure to Paigen high fat diet, and whether this vasomotor dysfunction involved nitric oxide (NO) and or endothelium derived hyperpolarization factors (EDHF). We utilised mice with hypomorphic ApoE lipoprotein that lacked SR-B1 (SR-B1-/-/ApoER61h/h, n = 8) or were heterozygous for SR-B1 (SR-B1+/-/ApoER61h/h, n = 8) to investigate coronary dilator function with synchrotron microangiography. Partially occlusive stenoses were observed in vivo in SR-B1 deficient mice only. Increases in artery-arteriole calibre to acetylcholine and sodium nitroprusside stimulation were absent in SR-B1 deficient mice. Residual dilation to acetylcholine following L-NAME (50 mg/kg) and sodium meclofenamate (3 mg/kg) blockade was present in both mouse groups, except at occlusions, indicating that EDHF was not impaired. We show that SR-B1 deficiency caused impairment of NO-mediated dilation of conductance and microvessels. Our findings also suggest EDHF and prostanoids are important for global perfusion, but ultimately the loss of NO-mediated vasodilation contributes to atherothrombotic progression in ischemic cardiomyopathy.
