PCSK9 regulates low density lipoprotein receptor (LDLR) levels and consequently is a target for the prevention of atherosclerosis and coronary heart disease.
CETP (cholesteryl ester transfer protein) and HL (hepatic lipase) play a role in the metabolism of plasma lipoproteins, but the effects of CETP and LIPC (gene encoding HL) genotypes on coronary atherosclerosis may be dependent on LDL (low-density lipoprotein)-receptor activity.
Moreover, of the 8 sex-biased genes at these loci, 4 have been directly linked to monogenic disorders of lipid metabolism and show an expression profile in females (elevated expression of ABCA1, APOA5 and LDLR; reduced expression of LIPC) that is consistent with the lower female risk of coronary artery disease.
Proprotein convertase subtilisin kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein (LDL) receptor (LDLR), and its deficiency in humans results in low plasma LDL cholesterol and protection against coronary heart disease.
Persons with hFH generally manifest elevations of low density lipoprotein (LDL) cholesterol throughout their lives and have a markedly increased risk of death from coronary artery disease.
This disease, which is due to mutation in the low density lipoprotein (LDL) receptor gene and results in deficiency of the LDL receptor, is associated with hypercholesterolemia and premature development of coronary heart disease.
Our findings provide new insights into LDL biology and show that targeting PCSK9 using heparan sulfate mimetics is a potential therapeutic strategy in coronary artery disease.PCSK9 interacts with LDL receptor, causing its degradation, and consequently reduces the clearance of LDL.Here, Gustafsen et al. show that PCSK9 interacts with heparan sulfate proteoglycans and this binding favors LDLR degradation.
The History of the WHHL Rabbit, an Animal Model of Familial Hypercholesterolemia (I) - Contribution to the Elucidation of the Pathophysiology of Human Hypercholesterolemia and Coronary Heart Disease.
These data confirm the genetic heterogeneity of LDLR mutations in the UK and the deleterious effect of mutations in exon 3 or 4 of LDLR on receptor function, lipids and severity of coronary heart disease.
Atherosclerosis-prone apolipoprotein E (apoE) or low-density lipoprotein receptor (LDL-R) knockout (KO) mice are generally resistant to developing coronary atherosclerosis (CA) and ischemic heart disease (IHD).
Although genes coding for PPARs (alpha, gamma), CD36, LDLR showed correlation with the severity of coronary atherosclerosis , blood cellular LXRalpha genomic profile showed conspicuous negative correlation with the severity of coronary atherosclerosis in subjects with or without hypercholesterolemia.
Familial hypercholesterolaemia is a co-dominant inherited disorder of lipoprotein metabolism, in which defects in the gene for the low-density-lipoprotein (LDL) receptor result in a twofold increase in the plasma concentration of cholesterol and moderate-to-severe premature coronary heart disease.
Our findings demonstrate that the Ldlr KO hamster is an animal model of choice for human FH and has great potential in translational research of hyperlipidemia and coronary heart disease.
Relationships of abdominal obesity and hyperinsulinemia to angiographically assessed coronary artery disease in men with known mutations in the LDL receptor gene.