Thieno[2,3-c]isoquinolin-5-one, a potent poly(ADP-ribose) polymerase inhibitor, promotes atherosclerotic plaque regression in high-fat diet-fed apolipoprotein E-deficient mice: effects on inflammatory markers and lipid content.

The Journal of Pharmacology and Experimental Therapeutics
C P HansA H Boulares

Abstract

We recently showed that poly(ADP-ribose) polymerase (PARP) is activated within atherosclerotic plaques in an animal model of atherosclerosis. Pharmacological inhibition of PARP or reduced expression in heterozygous animals interferes with atherogenesis and may promote factors of plaque stability, possibly reflecting changes in inflammatory and cellular factors consistent with plaque stability. The current study addresses the hypothesis that pharmacological inhibition of PARP promotes atherosclerotic plaque regression. Using a high-fat diet-induced atherosclerosis apolipoprotein E(-/-) mouse model, we demonstrate that administration of the potent PARP inhibitor, thieno[2,3-c]isoquinolin-5-one (TIQ-A), when combined with a regular diet regimen during treatment, induced regression of established plaques. Plaque regression was associated with a reduction in total cholesterol and low-density lipoproteins. Furthermore, plaques of TIQ-A-treated mice were highly enriched with collagen and smooth muscle cells, displayed thick fibrous caps, and exhibited a marked reduction in CD68-positive macrophage recruitment and associated foam cell presence. These changes correlated with a significant decrease in expression of monocyte chemoattracta...Continue Reading

References

Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·H C Ha, S H Snyder
Jun 18, 2002·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·I T Johnson
Jun 18, 2003·Cell·W Lee Kraus, John T Lis
Oct 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·James X RongEdward A Fisher
Mar 4, 2005·The International Journal of Biochemistry & Cell Biology·Mirella L Meyer-FiccaMyron K Jacobson
May 25, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Salvatore Cuzzocrea
Feb 14, 2006·The American Journal of Clinical Nutrition·Peter Libby
Mar 24, 2006·The New England Journal of Medicine·Sergio Fazio, MacRae Linton
Sep 18, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Yukio FujiwaraRyoji Nagai
Dec 21, 2007·Cardiovascular Research·Tobias von LukowiczChristian M Matter
Jan 29, 2008·Nature Clinical Practice. Cardiovascular Medicine·Kevin Jon WilliamsEdward A Fisher

❮ Previous
Next ❯

Citations

Feb 22, 2012·Nature Biotechnology·Elisabet WahlbergJohan Weigelt
Aug 5, 2011·European Journal of Medical Research·Christian ErbelG Szabo
Oct 2, 2012·FEBS Letters·Péter Bai, László Virág
Apr 27, 2010·Biochemical Pharmacology·Vincenzo GiansantiA Ivana Scovassi
Jan 26, 2018·Current Opinion in Lipidology·Amy C Burke, Murray W Huff
Oct 12, 2010·Journal of Cardiovascular Pharmacology·Fatemeh MoheimaniAntonio Ferrante
Jan 11, 2018·The Journal of Pharmacology and Experimental Therapeutics·Shishun HuangZhigang Wang
Nov 10, 2013·Cancers·Amanda F SwindallEddy S Yang
Aug 28, 2021·Progress in Lipid Research·Magdolna SzántóPeter Bai

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.