ArticleArteriosclerosis, thrombosis, and vascular biology2025
LDL-Bound PCSK9 Has a Slower Clearance Kinetic and Higher Use for HSPGs Than Free-PCSK9-Brief Report.
Silvia Cecilia Pacheco-Velázquez, Carlota Oleaga, Bastian Ramms, Joshua Hay, Paul A Mueller, Ester López-Aguilar, Joshua Miles, Ryan N Porell, Chelsea Cheng, Kamil Godula and 4 more
Abstract readComparative Study
In one paragraphArticle in Arteriosclerosis, thrombosis, and vascular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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What it found
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
14 authors.
Silvia Cecilia Pacheco-Velázquez *Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland (S.C.P.-V., C.O., J.H., P.A.M., J.M., H.T., S.F., N.P.).ORCID 0000-0002-6772-6389 Carlota Oleaga *Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland (S.C.P.-V., C.O., J.H., P.A.M., J.M., H.T., S.F., N.P.).ORCID 0000-0002-2146-9671 Bastian RammsDivision of Endocrinology and Metabolism, Department of Medicine (B.R., C.C., P.L.S.M.G.), University of California San Diego, La Jolla.ORCID 0000-0001-7238-8663 Joshua HayCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland (S.C.P.-V., C.O., J.H., P.A.M., J.M., H.T., S.F., N.P.).ORCID 0009-0000-7377-1269 Paul A MuellerCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland (S.C.P.-V., C.O., J.H., P.A.M., J.M., H.T., S.F., N.P.).ORCID 0000-0001-9315-0152 Ester López-AguilarDepartment of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Spain (E.L.-A.).ORCID 0000-0001-7343-9282 Joshua MilesCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland (S.C.P.-V., C.O., J.H., P.A.M., J.M., H.T., S.F., N.P.).ORCID 0000-0003-0022-1965 Ryan N PorellDepartment of Chemistry and Biochemistry (R.N.P., C.C., K.G.), University of California San Diego, La Jolla.
Chelsea ChengDivision of Endocrinology and Metabolism, Department of Medicine (B.R., C.C., P.L.S.M.G.), University of California San Diego, La Jolla.
Kamil GodulaDepartment of Chemistry and Biochemistry (R.N.P., C.C., K.G.), University of California San Diego, La Jolla.ORCID 0000-0001-7953-4619 Hagai TavoriCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland (S.C.P.-V., C.O., J.H., P.A.M., J.M., H.T., S.F., N.P.).ORCID 0000-0001-7553-9543 Philip L S M GordtsDivision of Endocrinology and Metabolism, Department of Medicine (B.R., C.C., P.L.S.M.G.), University of California San Diego, La Jolla.ORCID 0000-0001-7224-4328 Sergio FazioCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland (S.C.P.-V., C.O., J.H., P.A.M., J.M., H.T., S.F., N.P.).ORCID 0000-0002-8145-8034 Nathalie PamirCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland (S.C.P.-V., C.O., J.H., P.A.M., J.M., H.T., S.F., N.P.).ORCID 0000-0002-2074-888X Funding
Functional and structural correlates of PCSK9 association with lipoproteinsR01HL132985 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI PAMIR, NATHALIE · 2016 to 2024
$4.2MIn vivo glycan engineering at the cell-matrix interface to control stem cell fateDP2HD087954 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GODULA, KAMIL · 2015 to 2015
$2.3MCell membrane-targeting proteoglycan chimeras as selective growth factor signaling actuatorsR01GM145913 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kamil Godula · 2023 to 2026
$2.1MNHLBI NIH HHS R01 HL132985NICHD NIH HHS DP2 HD087954NIGMS NIH HHS R01 GM145913
6 · The paper itselfAbstract
backgroundHepatic heparan sulfate proteoglycans (HSPGs) accelerate the clearance of PCSK9 (proprotein convertase subtilisin/kexin type 9). We tested the hypothesis that free- and LDL (low-density lipoprotein)-bound PCSK9 forms have different HSPG-mediated clearance kinetics.
methodsMetabolic and turnover studies were performed after administration of free- and LDL-bound PCSK9 to 2 HSPG knockout mouse models: (1) Global knockout of syndecan-1 (
resultsThe clearance of both free- and LDL-bound PCSK9 followed a 2-phase decay behavior comprising a fast and a slow phase. The more notorious effect of HSPG deletion was on the slow phase: the clearance of free-PCSK9 was faster in
conclusionsThe clearance rate of plasma LDL-bound PCSK9 is slower than the clearance rate of its free form. The HSPG syndecan-1 modestly contributes to PCSK9 clearance through an LDLR-independent pathway.
Indexed as
Heparan Sulfate ProteoglycansLipoproteins, LDLLiverProprotein Convertase 9AnimalsHepatocytesKineticsMaleMiceMice, Inbred C57BLMice, KnockoutSulfotransferasesSyndecan-1Time FactorsHeparan Sulfate Proteoglycansheparitin sulfotransferaseLipoproteins, LDLPcsk9 protein, mouseProprotein Convertase 9Sdc1 protein, mouseSulfotransferasesSyndecan-1cholesterollipoproteinsmice, knockoutproteoglycanssyndecan-1
Identifiers
PMID40605748
PMCPMC13092286
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