Evidence mapPaperPMID 26522778Full record

ArticleJournal of lipid research2016

Evaluation of HDL-modulating interventions for cardiovascular risk reduction using a systems pharmacology approach.

Kapil Gadkar, James Lu, Srikumar Sahasranaman, John Davis, Norman A Mazer, Saroja Ramanujan

Open access · hybridAbstract readEvaluation Study
In one paragraph

Article in Journal of lipid research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.2field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Quantitative Systems Pharmacology: A Case for Disease Models.Clinical pharmacology and therapeutics · 2017
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Kapil GadkarGenentech Research and Early Development, South San Francisco, CA gadkar.kapil@gene.com.
James LuRoche Pharma Research and Early Development, Clinical Pharmacology, Disease Modeling Group, Roche Innovation Center Basel, Basel, Switzerland.
Srikumar SahasranamanGenentech Research and Early Development, South San Francisco, CA.
John DavisGenentech Research and Early Development, South San Francisco, CA.
Norman A MazerRoche Pharma Research and Early Development, Clinical Pharmacology, Disease Modeling Group, Roche Innovation Center Basel, Basel, Switzerland.
Saroja RamanujanGenentech Research and Early Development, South San Francisco, CA.
Roche (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The recent failures of cholesteryl ester transport protein inhibitor drugs to decrease CVD risk, despite raising HDL cholesterol (HDL-C) levels, suggest that pharmacologic increases in HDL-C may not always reflect elevations in reverse cholesterol transport (RCT), the process by which HDL is believed to exert its beneficial effects. HDL-modulating therapies can affect HDL properties beyond total HDL-C, including particle numbers, size, and composition, and may contribute differently to RCT and CVD risk. The lack of validated easily measurable pharmacodynamic markers to link drug effects to RCT, and ultimately to CVD risk, complicates target and compound selection and evaluation. In this work, we use a systems pharmacology model to contextualize the roles of different HDL targets in cholesterol metabolism and provide quantitative links between HDL-related measurements and the associated changes in RCT rate to support target and compound evaluation in drug development. By quantifying the amount of cholesterol removed from the periphery over the short-term, our simulations show the potential for infused HDL to treat acute CVD. For the primary prevention of CVD, our analysis suggests that the induction of ApoA-I synthesis may be a more viable approach, due to the long-term increase in RCT rate.

Indexed as

Apolipoprotein A-IBiological TransportBiomarkersCardiovascular DiseasesCholesterolCholesterol Ester Transfer ProteinsCholesterol, HDLHumansHypolipidemic AgentsLipoproteins, HDLModels, BiologicalQuinazolinesQuinazolinonesRisk FactorsUp-RegulationapabetaloneAPOA1 protein, humanApolipoprotein A-IBiomarkersCholesterolCholesterol Ester Transfer ProteinsCholesterol, HDLHypolipidemic AgentsLipoproteins, HDLQuinazolinesQuinazolinonesapolipoprotein A-Icholesterol metabolismcholesteryl ester transport proteinhigh density lipoproteinin-silico modellow density lipoproteinreverse cholesterol transport

Identifiers

PMID26522778
PMCPMC4689335
OpenAlexW2174424736

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.