Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism caused by mutations in the low-density lipoprotein receptor (LDL-R) gene, leading to elevated levels of cholesterol and an increased risk of coronary heart disease.
Familial hypercholesterolemia (FH), a major risk for coronary heart disease, is predominantly associated with mutations in the genes encoding the low-density lipoprotein receptor (LDLR) and its ligand apolipoprotein B (APOB).
Familial hypercholesterolemia (FH), a monogenic disease known to be caused by low-density lipoprotein receptor (LDLR) gene mutations, results in the development of premature atherosclerosis and coronary artery disease in affected individuals.
Familial hypercholesterolemia (FH), caused by low density lipoprotein (LDL) receptor (LDL-R) gene mutations, is associated with increased risk of premature coronary heart disease.
FH is caused by mutations in the low-density lipoprotein receptor (LDLR) gene and is characterized by raised plasma LDL-cholesterol, tendon xanthomas, and premature coronary heart disease.
Homozygotes and compound heterozygotes (i.e., those who carry two different FH genes) are very rare (one in 1,000,000) have severe hypercholesterolemia with xanthomas, and develop coronary heart disease early in life.
Homozygous FH having inheritance of two LDLR mutations is a rare but recognized syndrome associated with an extreme hypercholesterolaemia and early-onset coronary artery disease.
In this study, we firstly analyzed and found strong relationship between serum ox-HDL levels and risk factors of coronary artery diseases in clinic, then the effects of ox-HDL in initiation and progression of atherosclerosis in LDLR knockout mice were investigated by infusion of ox-HDL dissolved in chitosan hydrogel before the formation of lesions in vivo.
Increased expression of the low-density lipoprotein receptor (LDLR) is generally considered beneficial for reducing plasma cholesterol and atherosclerosis, and its downregulation has been thought to explain the association between apolipoprotein (apo) E4 and increased risk of coronary heart disease in humans.
Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease--a Mendelian Randomisation study.
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.
Mutations in the LDLR gene lead to increased plasma cholesterol levels, resulting in cholesterol deposition in the arteries, thereby increasing the risk of premature coronary heart disease.
Mutations in the LDL receptor (LDLR) or the apolipoprotein B-100 genes causing familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB), two of the most frequent inherited diseases, are the underlying genetic defects in a small proportion of patients suffering from premature atherosclerotic heart disease.
Mutations of low-density-lipoprotein-receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolaemia.
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.
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.
Patients with two abnormal LDL receptor genes (homozygous deficient patients) have severe hypercholesterolemia and life-threatening coronary artery disease in childhood.
PCSK9 gain of function mutations cause hypercholesterolaemia by a reduction of LDL receptor levels, while PCSK9 loss of function variants are associated with a reduction of LDL-C values and a decreased risk of coronary heart disease.
PCSK9 regulates low density lipoprotein receptor (LDLR) levels and consequently is a target for the prevention of atherosclerosis and 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.