title: Aortic calcification: Novel insights from familial hypercholesterolemia and potential role for the low-density lipoprotein receptor.
abstract: Once thought to be a passive process of calcium accrual in arterial vascular beds, vascular calcification is considered to be a tightly regulated process mediated by osteoblast-like cells under the dys-regulated interplay of shear stress, metabolites, cytokines and transcription factors. Unfortunately, without effective medical interventions to prevent or regress vascular calcification, this process directly contributes to cardiovascular morbidity and mortality. We have previously shown that patients with familial hypercholesterolemia (FH) have severe, premature aortic calcification and calcific aortic stenosis. We showed an age-related gene-dosage effect of deletion of the low-density lipoprotein receptor (LDL-R) gene on aortic calcification in human subjects with FH. The LDL-R deficient mouse and transgenic mice overexpressing the LDL-R degrading protein PCSK9 also exhibit aortic calcification, not fully explained by increased LDL cholesterol levels. Taken together, these data suggests a novel role for the LDL-R in the inhibition of vascular calcification. Understanding the molecular role of the LDL-R and its signaling partners in vascular calcification will be instrumental in identifying novel therapies for a common age-related process associated with a large burden of disease.
authors.affiliation: Division of Cardiology, Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fantus
authors.forename: Zuhier
authors.initials: Z
authors.lastname: Awan
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000209:etiology* / Q000235:genetics; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications*; D051379:Mice; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology*; D061205:Vascular Calcification / Q000209:etiology* / Q000235:genetics
chemical_list: D011973:Receptors, LDL