Table 2.
Vascular phenotypes from murine models of CBS deficiency
| References | |
|---|---|
| Endothelial dysfunction | |
| cbs+/− | |
| Aortic and mesenteric arteriolar endothelial dysfunction | 40, 174 |
| cbs−/− | |
| Cremasteric artery and aortic endothelial dysfunction | 74 |
| Vascular remodeling | |
| cbs+/− | |
| Aortic hypertrophy | 123 |
| Increased carotid artery neointima formation* | 152 |
| Increased aortic stiffness* | 150 |
| Increased carotid artery permeability* | 150 |
| Accelerated carotid artery thrombosis* | 32 |
| Mild left ventricular hypertrophy* | 94 |
| Impaired angiogenesis | |
| cbs+/− | |
| Impaired angiogenesis after hindlimb ischemia | 16 |
| Decreased carotid artery reendothelialization* | 152 |
| Dyslipidosis, thrombosis, and arteriosclerosis | |
| cbs−/− | |
| Abnormal lipid metabolism | 119 |
| Increased triglycerides and nonesterified fatty acids | |
| Decreased thiolase activity | |
| Decreased hepatic ApoB100 | |
| Increased serum ApoB100 and VLDL | |
| Decreased cholesterol/phospholipid in HDL-cholesterol but not total cholesterol | |
| Decreased lecithin-cholesterol acyltransferase activity | |
| Decreased liver paraoxonase 1 activity | |
| Differential expression of ATP-binding cassette transporters and genes involved in liver lipid homeostasis | 51, 53 |
| Reduced levels of the hepatocyte antiapoptotic factor DYRK1A | 55 |
| Redox disequilibrium in the liver, although attenuated by increased catalase activity | 56 |
| cbs−/−Cbs+/− | |
| Rescued hepatic steatosis and neonatal lethality of cbs−/− without lowering [Hcy] or rescuing hypercoagulability | 104 |
| cbs+/− | |
| Normal hepatic and plasma triglycerides, normal plasma cholesterol, and 44% greater hepatic cholesterol than cbs+/+ | 176 |
| Tg-S466L cbs−/− | |
| Monocytosis and enhanced plaque formation | 183 |
| cbs+/−ApoE−/− | |
| Increased thrombosis | 32, 178 |
| cbs+/−ApoA1+/− | |
| Hypertension and left ventricular hypertrophy | 20, 21 |
| Cerebrovascular dysfunction | |
| cbs+/− | |
| Cerebral arteriolar remodeling | 12 |
| Altered blood-brain barrier in permeability* | 77 |
cbs is the murine CBS gene and Cbs is the human CBS gene; thus, cbs−/− Cbs+/− mice are cbs−/− mice with heterozygous Cbs gene expression. Apo, apolipoprotein; Hcy, homocysteine.
*
With concomitant diet-induced hyperhomocysteinemia.