Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S]
L-4F, an apolipoprotein A-I (apoA-I) mimetic peptide (also known as APL180), was administered daily by either intravenous (IV) infusion for 7 days or by subcutaneous (SC) injection for 28 days in patients with coronary heart disease in two distinct clinical studies. L-4F was well tolerated at all do...
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doaj-bba86b6dfe5740d985bc87e52468c7182021-04-28T06:02:49ZengElsevierJournal of Lipid Research0022-22752011-02-01522361373Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S]Catherine E. Watson0Nicole Weissbach1Lise Kjems2Surya Ayalasomayajula3Yiming Zhang4Ih Chang5Mohamad Navab6Susan Hama7Greg Hough8Srinivasa T. Reddy9Daniel Soffer10Daniel J. Rader11Alan M. Fogelman12Alison Schecter13To whom correspondence should be addressed.; Novartis Institutes for Biomedical Research, Cambridge, MA 02139Novartis Institutes for Biomedical Research, Cambridge, MA 02139Novartis Institutes for Biomedical Research, Cambridge, MA 02139East Hanover, NJ 07936East Hanover, NJ 07936East Hanover, NJ 07936Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095Department of Medicine and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104Department of Medicine and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095Novartis Institutes for Biomedical Research, Cambridge, MA 02139L-4F, an apolipoprotein A-I (apoA-I) mimetic peptide (also known as APL180), was administered daily by either intravenous (IV) infusion for 7 days or by subcutaneous (SC) injection for 28 days in patients with coronary heart disease in two distinct clinical studies. L-4F was well tolerated at all doses tested. Despite achieving plasma levels (mean maximal plasma concentration of 2,907 ng/ml and 395 ng/ml, following IV infusion and SC injection, respectively), that were effective in previously published animal models, treatment with L-4F, as assessed by biomarkers of HDL function such as HDL-inflammatory index (HII), and paraoxonase activity, did not improve. Paradoxically, there was a 49% increase in high-sensitivity C-reactive protein (hs-CRP) levels after seven IV infusions of 30 mg L-4F (P < 0.05; compared with placebo) and a trend for hs-CRP increase in subjects receiving 30 mg SC injection for 28 days. In a subsequent, ex vivo study, addition of L-4F at concentrations of 150, 375, or 1,000 ng/ml to plasma from subjects prior to L-4F treatment resulted in significant dose-dependent HII improvement. In conclusion, in vivo L-4F treatment, delivered by either SC injection or IV infusion, did not improve HDL functional biomarkers despite achieving plasma levels that improved identical biomarkers ex vivo and in animal models.http://www.sciencedirect.com/science/article/pii/S0022227520405322apolipoproteinatherosclerosishigh density lipoproteinC-reactive proteincoronary heart diseasediabetes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Catherine E. Watson Nicole Weissbach Lise Kjems Surya Ayalasomayajula Yiming Zhang Ih Chang Mohamad Navab Susan Hama Greg Hough Srinivasa T. Reddy Daniel Soffer Daniel J. Rader Alan M. Fogelman Alison Schecter |
spellingShingle |
Catherine E. Watson Nicole Weissbach Lise Kjems Surya Ayalasomayajula Yiming Zhang Ih Chang Mohamad Navab Susan Hama Greg Hough Srinivasa T. Reddy Daniel Soffer Daniel J. Rader Alan M. Fogelman Alison Schecter Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S] Journal of Lipid Research apolipoprotein atherosclerosis high density lipoprotein C-reactive protein coronary heart disease diabetes |
author_facet |
Catherine E. Watson Nicole Weissbach Lise Kjems Surya Ayalasomayajula Yiming Zhang Ih Chang Mohamad Navab Susan Hama Greg Hough Srinivasa T. Reddy Daniel Soffer Daniel J. Rader Alan M. Fogelman Alison Schecter |
author_sort |
Catherine E. Watson |
title |
Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S] |
title_short |
Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S] |
title_full |
Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S] |
title_fullStr |
Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S] |
title_full_unstemmed |
Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S] |
title_sort |
treatment of patients with cardiovascular disease with l-4f, an apo-a1 mimetic, did not improve select biomarkers of hdl function[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2011-02-01 |
description |
L-4F, an apolipoprotein A-I (apoA-I) mimetic peptide (also known as APL180), was administered daily by either intravenous (IV) infusion for 7 days or by subcutaneous (SC) injection for 28 days in patients with coronary heart disease in two distinct clinical studies. L-4F was well tolerated at all doses tested. Despite achieving plasma levels (mean maximal plasma concentration of 2,907 ng/ml and 395 ng/ml, following IV infusion and SC injection, respectively), that were effective in previously published animal models, treatment with L-4F, as assessed by biomarkers of HDL function such as HDL-inflammatory index (HII), and paraoxonase activity, did not improve. Paradoxically, there was a 49% increase in high-sensitivity C-reactive protein (hs-CRP) levels after seven IV infusions of 30 mg L-4F (P < 0.05; compared with placebo) and a trend for hs-CRP increase in subjects receiving 30 mg SC injection for 28 days. In a subsequent, ex vivo study, addition of L-4F at concentrations of 150, 375, or 1,000 ng/ml to plasma from subjects prior to L-4F treatment resulted in significant dose-dependent HII improvement. In conclusion, in vivo L-4F treatment, delivered by either SC injection or IV infusion, did not improve HDL functional biomarkers despite achieving plasma levels that improved identical biomarkers ex vivo and in animal models. |
topic |
apolipoprotein atherosclerosis high density lipoprotein C-reactive protein coronary heart disease diabetes |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520405322 |
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