Sortilin and the risk of cardiovascular disease

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Maria Francisca Coutinho (Author) Other; Mafalda Bourbon (Author) Other; Maria João Prata (Author) FCUP; Sandra Alves (Author) Other

Journal

Title: Revista Portuguesa de Cardiologia

Vol. 32 No. 9

Pages: 793-799

ISSN: 0870-2551

Publisher: Sociedade Portuguesa De Cardiologia

Indexing

ISI Web of Knowledge - 4 Citations

Scopus - 6 Citations

Other information

Authenticus ID: P-008-HHJ

DOI: 10.1016/j.repc.2013.02.006

Abstract (EN): Plasma low-density lipoprotein cholesterol (LDL-C) levels are a key determinant of the risk of cardiovascular disease, which is why many studies have attempted to elucidate the pathways that regulate its metabolism. Novel Latest-generation sequencing techniques have identified a strong association between the 1p13 locus and the risk of cardiovascular disease caused by changes in plasma LDL-C levels. As expected for a complex phenotype, the effects of variation in this locus are only moderate. Even so, knowledge of the association is of major importance, since it has unveiled a new metabolic pathway regulating plasma cholesterol levels. Crucial to this discovery was the work of three independent teams seeking to clarify the biological basis of this association, who succeeded in proving that SORT1, encoding sortilin, was the gene in the 1p13 locus involved in LDL metabolism. SORT1 was the first gene identified as determining plasma LDL levels to be mechanistically evaluated and, although the three teams used different, though appropriate, experimental methods, their results were in some ways contradictory. Here we review all the experiments that led to the identification of the new pathway connecting sortilin with plasma LDL levels and risk of myocardial infarction. The regulatory mechanism underlying this association remains unclear, but its discovery has paved the way for considering previously unsuspected therapeutic targets and approaches.

Language: Portuguese

Type (Professor's evaluation): Scientific

No. of pages: 7