Lipoprotein(a) Particle Production as a Determinant of Plasma Lipoprotein(a) Concentration Across Varying Apolipoprotein(a) Isoform Sizes and Background Cholesterol-Lowering Therapy.
Background Elevated lipoprotein(a) (Lp(a)), a low-density lipoprotein-like particle bound to the polymorphic apolipoprotein(a) (apo(a)), may be causal for cardiovascular disease. However, the metabolism of Lp(a) in humans is poorly understood. Methods and Results We investigated the kinetics of Lp(a...
| Publicado en: | Journal of the American Heart Association Vol. 8; no. 7; pp. 1 - 13 |
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| Autores principales: | , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Wiley-Blackwell
4/2/2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=135675983&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 135675983 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20479980 FSQ9 jtl: Journal of the American Heart Association issn: 20479980 maglogo: Y pubinfo: dt: 4/2/2019 vid: 8 iid: 7 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 135675983 135675983 NLM30897995 135675983 10.1161/JAHA.118.011781 NLM30897995 135675983 ppf: 1 ppct: 12 formats: tig: atl: Lipoprotein(a) Particle Production as a Determinant of Plasma Lipoprotein(a) Concentration Across Varying Apolipoprotein(a) Isoform Sizes and Background Cholesterol-Lowering Therapy. aug: au: Chan, Dick C. Watts, Gerald F. Coll, Blai Wasserman, Scott M. Marcovina, Santica M. Barrett, P. Hugh R. affil: Schools of Medicine University of Western Australia, Perth, Australia sug: subj: Apolipoproteins Lipoproteins, LDL Cholesterol Metabolism Male Adult Lipoproteins, HDL Cholesterol Metabolism Human Young Adult Hypercholesterolemia, Familial Blood Antilipemic Agents Therapeutic Use Lipoproteins Metabolism Adolescence Proteins Lipoproteins Blood Hypercholesterolemia, Familial Prevention and Control Aged Middle Age Validation Studies Comparative Studies Evaluation Research Multicenter Studies Scales Adult: 19-44 years Adolescent: 13-18 years Aged: 65+ years Middle Aged: 45-64 years Male ab: Background Elevated lipoprotein(a) (Lp(a)), a low-density lipoprotein-like particle bound to the polymorphic apolipoprotein(a) (apo(a)), may be causal for cardiovascular disease. However, the metabolism of Lp(a) in humans is poorly understood. Methods and Results We investigated the kinetics of Lp(a)-apo(a) and low-density lipoprotein-apoB-100 in 63 normolipidemic men. The fractional catabolic rate ( FCR ) and production rate PR ) were studied. Plasma apo(a) concentration was significantly and inversely associated with apo(a) isoform size ( r=-0.536, P<0.001) and apo(a) FCR ( r=-0.363, P<0.01), and positively with apo(a) PR ( r=0.877, P<0.001). There were no significant associations between the FCR s of apo(a) and low-density lipoprotein-apoB-100. Subjects with smaller apo(a) isoform sizes (≤22 kringle IV repeats) had significantly higher apo(a) PR ( P<0.05) and lower apo(a) FCR ( P<0.01) than those with larger sizes. Plasma apo(a) concentration was significantly associated with apo(a) PR ( r=0.930, P<0.001), but not with FCR ( r=-0.012, P>0.05) in subjects with smaller apo(a) isoform size. In contrast, both apo(a) PR and FCR were significantly associated with plasma apo(a) concentrations ( r=0.744 and -0.389, respectively, P<0.05) in subjects with larger isoforms. In multiple regression analysis, apo(a) PR and apo(a) isoform size were significant predictors of plasma apo(a) concentration independent of low-density lipoprotein-apoB-100 FCR and background therapy with atorvastatin and evolocumab. Conclusions In normolipidemic men, the plasma Lp(a) concentration is predominantly determined by the rate of production of Lp(a) particles, irrespective of apo(a) isoform size and background therapy with a statin and a proprotein convertase subtilisin-kexin type 9 inhibitor. Our findings underscore the importance of therapeutic targeting of the hepatic synthesis and secretion of Lp(a) particles. Lp(a) particle catabolism may only play a modest role in determining Lp(a) concentration in subjects with larger apo(a) isoform size. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02189837. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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