| First Author | Liao D | Year | 2006 |
| Journal | Circ Res | Volume | 99 |
| Issue | 6 | Pages | 598-606 |
| PubMed ID | 16931800 | Mgi Jnum | J:125063 |
| Mgi Id | MGI:3723413 | Doi | 10.1161/01.RES.0000242559.42077.22 |
| Citation | Liao D, et al. (2006) Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance. Circ Res 99(6):598-606 |
| abstractText | We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) mice. We observed that plasma homocysteine (Hcy) concentrations are negatively correlated with HDL-C and apolipoprotein A1 (apoA-I) in patients with CAD. We found the loss of large HDL particles, increased HDL-free cholesterol, and decreased HDL protein in CBS(-/-)/apoE(-/-) mice, and attenuated cholesterol efflux from cholesterol-loaded macrophages to plasma in CBS(-/-)/apoE(-/-) mice. ApoA-I protein was reduced in the plasma and liver, but hepatic apoA-I mRNA was unchanged in CBS(-/-)/apoE(-/-) mice. Moreover, Hcy (0.5 to 2 mmol/L) reduced the levels of apoA-I protein but not mRNA and inhibited apoA-1 protein synthesis in mouse primary hepatocytes. Further, plasma lecithin:cholesterol acyltransferase (LCAT) substrate reactivity was decreased, LCAT specific activity increased, and plasma LCAT protein levels unchanged in apoE(-/-)/CBS(-/-) mice. Finally, the clearance of plasma HDL cholesteryl ester, but not HDL protein, was faster in CBS(-/-)/apoE(-/-) mice, correlated with increased scavenger receptor B1, and unchanged ATP-binding cassette transporter A1 protein expression in the liver. These findings indicate that HHcy inhibits reverse cholesterol transport by reducing circulating HDL via inhibiting apoA-I protein synthesis and enhancing HDL-C clearance. |
