Abstract
BackgroundSortilin is a 95-kDa protein which has recently been linked to circulating cholesterol concentration and lifetime risk of developing significant atherosclerotic disease. Sortilin is found inside different cell types and circulating in blood. Higher circulating sortilin concentration has been found in patients with coronary atherosclerosis compared to control subjects. Sortilin concentration is influenced by statin therapy.MethodsWe enrolled statin-naïve subjects with type 2 diabetes mellitus and we performed a cross-sectional study to evaluate the association between sortilin levels and the presence of clinically significant lower limb peripheral artery disease (PAD) in a population of statin-free diabetic subjects.ResultsOut of the 154 patients enrolled in our study, 80 patients were free from PAD, while 74 had clinically significant PAD. Sortilin concentration was significantly higher in the latter group compared to the former (1.61 ± 0.54 ng/mL versus 0.67 ± 0.30 ng/mL, P < 0.01) and there was a trend toward increased sortilin levels as disease severity increased. The association of sortilin levels with PAD remained after adjusting for major risk factors in a multivariate analysis.ConclusionsWe showed that sortilin is significantly and independently associated with the presence of lower limb PAD in a statin-free diabetic population and it may be a promising marker for clinically significant atherosclerosis of the lower limbs. Further studies are needed to confirm this finding and to evaluate its clinical usefulness.
Highlights
Sortilin is a 95-kDa protein which has recently been linked to circulating cholesterol concentration and lifetime risk of developing significant atherosclerotic disease
Sortilin is codified on chromosome 13 by the gene SORT1, whose polymorphisms have been linked with circulating levels of low-density lipoprotein (LDL)
Eighty of the patients did not fulfill the criteria for a diagnosis of peripheral artery disease (PAD), while the remaining 74 had a confirmed diagnosis of PAD or received a diagnosis of PAD during the index hospitalization
Summary
Sortilin is a 95-kDa protein which has recently been linked to circulating cholesterol concentration and lifetime risk of developing significant atherosclerotic disease. Sortilin is found inside different cell types and circulating in blood. A 95-kDa protein mainly expressed in hepatocytes, takes part in intracellular protein sorting between the trans-Golgi network and endosomes [1]. It is expressed on cell membrane and small quantities of sortilin have been found in circulating form. Sortilin is codified on chromosome 13 by the gene SORT1, whose polymorphisms have been linked with circulating levels of low-density lipoprotein (LDL). Sortilin seems to take part in apolipoproteins trafficking inside hepatocytes, binding to apoB100 and promoting its trafficking to endosomal system, thereby promoting its degradation and reducing circulating levels of very low-density lipoprotein (VLDL). After the discovery of its link to atherosclerosis, there has been considerable interest in elucidating additional functions of sortilin in different cell types. Sortilin has been discovered to play a role in intracellular cytokine traffic [18, 19] and to be expressed in platelets, from where it is released after
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