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.
We concluded that the heterozygosity in LDLR-rs72658855and rs2228671 and T allele in LDLRrs2228671are strongly associated with an increased susceptibility to coronary artery disease.
Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism that mainly occurs due to mutations in the low-density lipoprotein receptor gene and is characterized by increased levels of low-density lipoprotein cholesterol, leading to accelerated atherogenesis and premature coronary heart disease.
Mutations in the LDLR gene lead to a reduced hepatic clearance of LDL as well as a high risk of coronary artery disease (CAD) and sudden cardiac death (SCD).
The proportion of LDLR pathogenic variants was higher in patients with a younger age of coronary artery disease (CAD) onset and significantly decreased as the age of CAD onset increased.
Furthermore, the PRS identified about 6% to 7% of individuals at CAD risk similar to carriers of the LDLR delta >15 kb mutation, consistent with previous estimates.
Familial hypercholesterolemia (FH) is reportedly associated with the development of coronary artery disease (CAD), especially acute coronary syndrome (ACS).
Familial hypercholesterolemia (FH) is an inherited disease of lipoprotein metabolism caused by a defect in the LDL receptor (LDLR) leading to severe hypercholesterolemia, and associated with an increased risk of coronary heart disease and myocardial infarction.
We observed that the genes like GALNT2, HMGCR were hypermethylated in the promoter whereas LDLR gene promoter was hypomethylated indicating that intracellular LDL uptake was higher in CAD patients.
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.
Familial Hypercholesterolemia (FH) is a common genetic disorder caused most often by mutations in the Low Density Lipoprotein Receptor gene (LDLr) leading to high blood cholesterol levels, and ultimately to development of premature coronary heart disease.
Background and Purpose- Familial hypercholesterolemia (FH) is a common autosomal dominant disease leading to increased level of serum LDL (low-density lipoprotein) cholesterol and risk 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.
In the patients carrying LDLR mutations and aged ≥ 30 years, the additional PCSK9 V4I variant was linked to a significantly increased prevalence of CAD in accord with the elevation of the LDL-cholesterol level.
We aimed to examine whether the most electronegative subfraction of low-density lipoprotein (LDL), L5, is correlated with QTc prolongation in patients with coronary artery disease (CAD) and investigate the effects of human L5 on the electrophysiological properties of cardiomyocytes in relation to the lectin-like oxidized LDL receptor (LOX-1).
The independent variants at PCSK9, HMGCR, LPA, APOA5 and LDLR were also associated with increased risk of coronary artery disease in the expected direction.