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Published in: Cardiovascular Diabetology 1/2019

Open Access 01-12-2019 | Arterial Occlusive Disease | Original investigation

Sortilin levels are associated with peripheral arterial disease in type 2 diabetic subjects

Authors: Federico Biscetti, Nicola Bonadia, Francesco Santini, Flavia Angelini, Elisabetta Nardella, Dario Pitocco, Angelo Santoliquido, Marco Filipponi, Raffaele Landolfi, Andrea Flex

Published in: Cardiovascular Diabetology | Issue 1/2019

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Abstract

Background

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. Higher circulating sortilin concentration has been found in patients with coronary atherosclerosis compared to control subjects. Sortilin concentration is influenced by statin therapy.

Methods

We 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.

Results

Out 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.

Conclusions

We 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.
Literature
1.
go back to reference Petersen CM, Nielsen MS, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen HH, et al. Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography. J Biol Chem. 1997;272:3599–605.CrossRef Petersen CM, Nielsen MS, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen HH, et al. Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography. J Biol Chem. 1997;272:3599–605.CrossRef
2.
go back to reference Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, et al. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357:443–53.CrossRef Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, et al. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357:443–53.CrossRef
3.
go back to reference Kathiresan S, Manning AK, Demissie S, D’Agostino RB, Surti A, Guiducci C, et al. A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study. BMC Med Genet. 2007;8(Suppl 1):S17.CrossRef Kathiresan S, Manning AK, Demissie S, D’Agostino RB, Surti A, Guiducci C, et al. A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study. BMC Med Genet. 2007;8(Suppl 1):S17.CrossRef
4.
go back to reference Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet. 2008;40:189–97.CrossRef Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet. 2008;40:189–97.CrossRef
5.
go back to reference Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008;40:161–9.CrossRef Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008;40:161–9.CrossRef
6.
go back to reference Wallace C, Newhouse SJ, Braund P, Zhang F, Tobin M, Falchi M, et al. Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia. Am J Hum Genet. 2008;82:139–49.CrossRef Wallace C, Newhouse SJ, Braund P, Zhang F, Tobin M, Falchi M, et al. Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia. Am J Hum Genet. 2008;82:139–49.CrossRef
7.
go back to reference Kathiresan S, Willer CJ, Peloso GM, Demissie S, Musunuru K, Schadt EE, et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet. 2009;41:56–65.CrossRef Kathiresan S, Willer CJ, Peloso GM, Demissie S, Musunuru K, Schadt EE, et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet. 2009;41:56–65.CrossRef
8.
go back to reference Aulchenko YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, Pramstaller PP, et al. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet. 2009;41:47–55.CrossRef Aulchenko YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, Pramstaller PP, et al. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet. 2009;41:47–55.CrossRef
9.
go back to reference Chasman DI, Paré G, Mora S, Hopewell JC, Peloso G, Clarke R, et al. Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis. PLoS Genet. 2009;5:e1000730.CrossRef Chasman DI, Paré G, Mora S, Hopewell JC, Peloso G, Clarke R, et al. Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis. PLoS Genet. 2009;5:e1000730.CrossRef
10.
go back to reference Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466:707–13.CrossRef Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466:707–13.CrossRef
11.
go back to reference Myocardial Infarction Genetics Consortium, Kathiresan S, Voight BF, Purcell S, Musunuru K, Ardissino D, et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41:334–41.CrossRef Myocardial Infarction Genetics Consortium, Kathiresan S, Voight BF, Purcell S, Musunuru K, Ardissino D, et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41:334–41.CrossRef
12.
go back to reference Schunkert H, König IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011;43:333–8.CrossRef Schunkert H, König IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011;43:333–8.CrossRef
13.
go back to reference Kjolby M, Andersen OM, Breiderhoff T, Fjorback AW, Pedersen KM, Madsen P, et al. Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export. Cell Metab. 2010;12:213–23.CrossRef Kjolby M, Andersen OM, Breiderhoff T, Fjorback AW, Pedersen KM, Madsen P, et al. Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export. Cell Metab. 2010;12:213–23.CrossRef
14.
go back to reference Linsel-Nitschke P, Heeren J, Aherrahrou Z, Bruse P, Gieger C, Illig T, et al. Genetic variation at chromosome 1p13.3 affects sortilin mRNA expression, cellular LDL-uptake and serum LDL levels which translates to the risk of coronary artery disease. Atherosclerosis. 2010;208:183–9.CrossRef Linsel-Nitschke P, Heeren J, Aherrahrou Z, Bruse P, Gieger C, Illig T, et al. Genetic variation at chromosome 1p13.3 affects sortilin mRNA expression, cellular LDL-uptake and serum LDL levels which translates to the risk of coronary artery disease. Atherosclerosis. 2010;208:183–9.CrossRef
15.
go back to reference Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature. 2010;466:714–9.CrossRef Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature. 2010;466:714–9.CrossRef
16.
go back to reference Strong A, Rader DJ. Sortilin as a regulator of lipoprotein metabolism. Curr Atheroscler Rep. 2012;14:211–8.CrossRef Strong A, Rader DJ. Sortilin as a regulator of lipoprotein metabolism. Curr Atheroscler Rep. 2012;14:211–8.CrossRef
17.
go back to reference Strong A, Ding Q, Edmondson AC, Millar JS, Sachs KV, Li X, et al. Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism. J Clin Invest. 2012;122:2807–16.CrossRef Strong A, Ding Q, Edmondson AC, Millar JS, Sachs KV, Li X, et al. Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism. J Clin Invest. 2012;122:2807–16.CrossRef
18.
go back to reference Herda S, Raczkowski F, Mittrücker HW, Willimsky G, Gerlach K, Kühl AA, et al. The sorting receptor sortilin exhibits a dual function in exocytic trafficking of interferon-γ and granzyme A in T cells. Immunity. 2012;37:854–66.CrossRef Herda S, Raczkowski F, Mittrücker HW, Willimsky G, Gerlach K, Kühl AA, et al. The sorting receptor sortilin exhibits a dual function in exocytic trafficking of interferon-γ and granzyme A in T cells. Immunity. 2012;37:854–66.CrossRef
19.
go back to reference Yabe-Wada T, Matsuba S, Takeda K, Sato T, Suyama M, Ohkawa Y, et al. TLR signals posttranscriptionally regulate the cytokine trafficking mediator sortilin. Sci Rep. 2016;6:26566.CrossRef Yabe-Wada T, Matsuba S, Takeda K, Sato T, Suyama M, Ohkawa Y, et al. TLR signals posttranscriptionally regulate the cytokine trafficking mediator sortilin. Sci Rep. 2016;6:26566.CrossRef
20.
go back to reference Ogawa K, Ueno T, Iwasaki T, Kujiraoka T, Ishihara M, Kunimoto S, et al. Soluble sortilin is released by activated platelets and its circulating levels are associated with cardiovascular risk factors. Atherosclerosis. 2016;249:110–5.CrossRef Ogawa K, Ueno T, Iwasaki T, Kujiraoka T, Ishihara M, Kunimoto S, et al. Soluble sortilin is released by activated platelets and its circulating levels are associated with cardiovascular risk factors. Atherosclerosis. 2016;249:110–5.CrossRef
21.
go back to reference Patel KM, Strong A, Tohyama J, Jin X, Morales CR, Billheimer J, et al. Macrophage sortilin promotes LDL uptake, foam cell formation, and atherosclerosis. Circ Res. 2015;116:789–96.CrossRef Patel KM, Strong A, Tohyama J, Jin X, Morales CR, Billheimer J, et al. Macrophage sortilin promotes LDL uptake, foam cell formation, and atherosclerosis. Circ Res. 2015;116:789–96.CrossRef
22.
go back to reference Mortensen MB, Kjolby M, Gunnersen S, Larsen JV, Palmfeldt J, Falk E, et al. Targeting sortilin in immune cells reduces proinflammatory cytokines and atherosclerosis. J Clin Invest. 2014;124:5317–22.CrossRef Mortensen MB, Kjolby M, Gunnersen S, Larsen JV, Palmfeldt J, Falk E, et al. Targeting sortilin in immune cells reduces proinflammatory cytokines and atherosclerosis. J Clin Invest. 2014;124:5317–22.CrossRef
23.
go back to reference Li J, Matye DJ, Li T. Insulin resistance induces posttranslational hepatic sortilin 1 degradation in mice. J Biol Chem. 2015;290:11526–36.CrossRef Li J, Matye DJ, Li T. Insulin resistance induces posttranslational hepatic sortilin 1 degradation in mice. J Biol Chem. 2015;290:11526–36.CrossRef
24.
go back to reference Chamberlain JM, O’Dell C, Sparks CE, Sparks JD. Insulin suppression of apolipoprotein B in McArdle RH7777 cells involves increased sortilin 1 interaction and lysosomal targeting. Biochem Biophys Res Commun. 2013;430:66–71.CrossRef Chamberlain JM, O’Dell C, Sparks CE, Sparks JD. Insulin suppression of apolipoprotein B in McArdle RH7777 cells involves increased sortilin 1 interaction and lysosomal targeting. Biochem Biophys Res Commun. 2013;430:66–71.CrossRef
25.
go back to reference Bi L, Chiang JYL, Ding W-X, Dunn W, Roberts B, Li T. Saturated fatty acids activate ERK signaling to downregulate hepatic sortilin 1 in obese and diabetic mice. J Lipid Res. 2013;54:2754–62.CrossRef Bi L, Chiang JYL, Ding W-X, Dunn W, Roberts B, Li T. Saturated fatty acids activate ERK signaling to downregulate hepatic sortilin 1 in obese and diabetic mice. J Lipid Res. 2013;54:2754–62.CrossRef
26.
go back to reference Oh TJ, Ahn CH, Kim BR, Kim KM, Moon JH, Lim S, et al. Circulating sortilin level as a potential biomarker for coronary atherosclerosis and diabetes mellitus. Cardiovasc Diabetol. 2017;16:1–7.CrossRef Oh TJ, Ahn CH, Kim BR, Kim KM, Moon JH, Lim S, et al. Circulating sortilin level as a potential biomarker for coronary atherosclerosis and diabetes mellitus. Cardiovasc Diabetol. 2017;16:1–7.CrossRef
28.
go back to reference Ohashi K, Shibata R, Murohara T, Ouchi N. Role of anti-inflammatory adipokines in obesity-related diseases. Trends Endocrinol Metab. 2014;25:348–55.CrossRef Ohashi K, Shibata R, Murohara T, Ouchi N. Role of anti-inflammatory adipokines in obesity-related diseases. Trends Endocrinol Metab. 2014;25:348–55.CrossRef
29.
go back to reference Strong A, Patel K, Rader DJ. Sortilin and lipoprotein metabolism: making sense out of complexity. Curr Opin Lipidol. 2014;25:350–7.CrossRef Strong A, Patel K, Rader DJ. Sortilin and lipoprotein metabolism: making sense out of complexity. Curr Opin Lipidol. 2014;25:350–7.CrossRef
30.
go back to reference Nozue T, Hattori H, Ogawa K, Kujiraoka T, Iwasaki TMI. Effects of statin therapy on plasma proprotein convertase subtilisin/kexin type 9 and sortilin levels in statin-naive patients with coronary artery disease. J Atheroscler Thromb. 2016;1:848–56.CrossRef Nozue T, Hattori H, Ogawa K, Kujiraoka T, Iwasaki TMI. Effects of statin therapy on plasma proprotein convertase subtilisin/kexin type 9 and sortilin levels in statin-naive patients with coronary artery disease. J Atheroscler Thromb. 2016;1:848–56.CrossRef
32.
go back to reference Bosch J, Eikelboom JW, Connolly SJ, Bruns NC, Lanius V, Yuan F, et al. Rationale, design and baseline characteristics of participants in the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial. Can J Cardiol. 2017;33:1027–35.CrossRef Bosch J, Eikelboom JW, Connolly SJ, Bruns NC, Lanius V, Yuan F, et al. Rationale, design and baseline characteristics of participants in the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial. Can J Cardiol. 2017;33:1027–35.CrossRef
33.
go back to reference Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377:1319–30.CrossRef Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377:1319–30.CrossRef
34.
go back to reference Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines. Circulation. 2017;135:e686–725.PubMed Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines. Circulation. 2017;135:e686–725.PubMed
35.
go back to reference Aboyans V, Ricco J-B, Bartelink M-LEL, Björck M, Brodmann M, Cohnert T, et al. ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal. Eur Heart J. 2017;2018(39):763–816. Aboyans V, Ricco J-B, Bartelink M-LEL, Björck M, Brodmann M, Cohnert T, et al. ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal. Eur Heart J. 2017;2018(39):763–816.
36.
go back to reference Becker F. Exploration of arterial function with noninvasive technics. Results in chronic arterial occlusive disease of the lower limbs according to Leriche and Fontaine classification. Int Angiol. 1985;4:311–22.PubMed Becker F. Exploration of arterial function with noninvasive technics. Results in chronic arterial occlusive disease of the lower limbs according to Leriche and Fontaine classification. Int Angiol. 1985;4:311–22.PubMed
37.
go back to reference Hardman RL, Jazaeri O, Yi J, Smith M, Gupta R. Overview of classification systems in peripheral artery disease. Semin Interv Radiol. 2014;31:378–88.CrossRef Hardman RL, Jazaeri O, Yi J, Smith M, Gupta R. Overview of classification systems in peripheral artery disease. Semin Interv Radiol. 2014;31:378–88.CrossRef
38.
go back to reference Choi SW, Kim HY, Lee YH, Ryu SY, Kweon SS, Rhee JA, et al. EGFR is associated with subclinical atherosclerosis independent of albuminuria: the Dong-gu study. Atherosclerosis. 2010;212:616–67. Choi SW, Kim HY, Lee YH, Ryu SY, Kweon SS, Rhee JA, et al. EGFR is associated with subclinical atherosclerosis independent of albuminuria: the Dong-gu study. Atherosclerosis. 2010;212:616–67.
39.
go back to reference American Diabetes Association. Peripheral artery disease in people with diabetes. Diabetes Care. 2003;26:3333–41.CrossRef American Diabetes Association. Peripheral artery disease in people with diabetes. Diabetes Care. 2003;26:3333–41.CrossRef
40.
go back to reference Nativel M, Potier L, Alexandre L, Baillet-Blanco L, Ducasse E, Velho G, et al. Lower extremity arterial disease in patients with diabetes: a contemporary narrative review. Cardiovasc Diabetol. 2018;17:138.CrossRef Nativel M, Potier L, Alexandre L, Baillet-Blanco L, Ducasse E, Velho G, et al. Lower extremity arterial disease in patients with diabetes: a contemporary narrative review. Cardiovasc Diabetol. 2018;17:138.CrossRef
41.
go back to reference Schneider F, Saulnier PJ, Gand E, Desvergnes M, Lefort N, Thorin E, et al. Influence of micro- and macro-vascular disease and Tumor Necrosis Factor Receptor 1 on the level of lower-extremity amputation in patients with type 2 diabetes. Cardiovasc Diabetol. 2018;17:81.CrossRef Schneider F, Saulnier PJ, Gand E, Desvergnes M, Lefort N, Thorin E, et al. Influence of micro- and macro-vascular disease and Tumor Necrosis Factor Receptor 1 on the level of lower-extremity amputation in patients with type 2 diabetes. Cardiovasc Diabetol. 2018;17:81.CrossRef
42.
go back to reference Giovannini S, Tinelli G, Biscetti F, Straface G, Angelini F, Pitocco D, et al. Serum high mobility group box-1 and osteoprotegerin levels are associated with peripheral arterial disease and critical limb ischemia in type 2 diabetic subjects. Cardiovasc Diabetol. 2017;16:99.CrossRef Giovannini S, Tinelli G, Biscetti F, Straface G, Angelini F, Pitocco D, et al. Serum high mobility group box-1 and osteoprotegerin levels are associated with peripheral arterial disease and critical limb ischemia in type 2 diabetic subjects. Cardiovasc Diabetol. 2017;16:99.CrossRef
43.
go back to reference He X, Hu X, Ma X, Su H, Ying L, Peng J, et al. Elevated serum fibroblast growth factor 23 levels as an indicator of lower extremity atherosclerotic disease in Chinese patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2017;16:77.CrossRef He X, Hu X, Ma X, Su H, Ying L, Peng J, et al. Elevated serum fibroblast growth factor 23 levels as an indicator of lower extremity atherosclerotic disease in Chinese patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2017;16:77.CrossRef
44.
go back to reference Hagita S, Rogers MA, Pham T, Wen JR, Mlynarchik AK, Aikawa M, et al. Transcriptional control of intestinal cholesterol absorption, adipose energy expenditure and lipid handling by Sortilin. Sci Rep. 2018;8:9006.CrossRef Hagita S, Rogers MA, Pham T, Wen JR, Mlynarchik AK, Aikawa M, et al. Transcriptional control of intestinal cholesterol absorption, adipose energy expenditure and lipid handling by Sortilin. Sci Rep. 2018;8:9006.CrossRef
45.
go back to reference Amengual J, Guo L, Strong A, Madrigal-Matute J, Wang H, Kaushik S, et al. Autophagy is required for sortilin-mediated degradation of apolipoprotein B100. Circ Res. 2018;122:568–82.CrossRef Amengual J, Guo L, Strong A, Madrigal-Matute J, Wang H, Kaushik S, et al. Autophagy is required for sortilin-mediated degradation of apolipoprotein B100. Circ Res. 2018;122:568–82.CrossRef
46.
go back to reference Hu D, Yang Y, Peng DQ. Increased sortilin and its independent effect on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in statin-naive patients with coronary artery disease. Int J Cardiol. 2017;227:61–5.CrossRef Hu D, Yang Y, Peng DQ. Increased sortilin and its independent effect on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in statin-naive patients with coronary artery disease. Int J Cardiol. 2017;227:61–5.CrossRef
Metadata
Title
Sortilin levels are associated with peripheral arterial disease in type 2 diabetic subjects
Authors
Federico Biscetti
Nicola Bonadia
Francesco Santini
Flavia Angelini
Elisabetta Nardella
Dario Pitocco
Angelo Santoliquido
Marco Filipponi
Raffaele Landolfi
Andrea Flex
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2019
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-019-0805-5

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