Cytokines, macrophage lipid metabolism and foam cells: Implications for cardiovascular disease therapy

McLaren, James E.; Michael, Daryn Robert; Ashlin, Timothy Gordon; Ramji, Dipak Purshottam

doi:10.1016/j.plipres.2011.04.002

Cited by 321 publications

(389 citation statements)

References 181 publications

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“…Both the innate and adaptive immune response in atherosclerosis is organized by a range of cytokines, which regulate all stages of the disease. 21 Noninvasive imaging techniques can be used to detect and monitor preclinical atherosclerosis in human arteries. The use of CIMT and CCS to detect subclinical atherosclerosis has become a topical issue and many studies of this subject have been conducted.…”

Section: Discussionmentioning

confidence: 99%

A coronary proatherosclerotic marker: Pregnancy-associated plasma protein A and its association with coronary calcium score and carotid intima-media thickness

Guven

Demircelik²,

Gürel

et al. 2017

Adv Clin Exp Med

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Section: Discussionmentioning

confidence: 99%

A coronary proatherosclerotic marker: Pregnancy-associated plasma protein A and its association with coronary calcium score and carotid intima-media thickness

Guven

Demircelik²,

Gürel

et al. 2017

Adv Clin Exp Med

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“…Macrophages are known to play an important role in atherosclerosis formation [17] and the associated inflammatory pathways [18]. High levels of plasma LDL lead to oxidative modification of those LDL particles in the arterial intima, thus forming oxLDL particles [19].…”

Section: Editorialmentioning

confidence: 99%

“…facilitating LRP-1 degradation) [16], suggesting that PCSK9 inhibition would prevent this component of the inflammatory cascade in response to the molecular triggers of LRP-1 (e.g. lipopolysaccharides encountered on Gram negative bacterial surfaces, cell debris released during an acute MI), and thus PCSK9 inhibitors could promote an antiinflammatory effect.Macrophages are known to play an important role in atherosclerosis formation [17] and the associated inflammatory pathways [18]. High levels of plasma LDL lead to oxidative modification of those LDL particles in the arterial intima, thus forming oxLDL particles [19].…”

mentioning

confidence: 99%

PCSK9 Inhibition in Acute Myocardial Infarction: A Novel Opportunity

Trankle¹,

Abbate²

2016

Transl Med (sunnyvale)

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EditorialAcute myocardial infarction (AMI) remains a leading cause of mortality and morbidity across the nation and worldwide. While major advances in reperfusion strategies over the past several decades have significantly reduced early mortality rates after AMI, patients who survive the index event are at increasingly risk for adverse cardiac remodeling and the sequelae of heart failure and sudden cardiac death [1]. This problem is accelerated by the aging population, making heart failure a major public health concern. Heart failure indeed currently affects approximately 5 million Americans, with increasing rates of prevalence and incidence.Anticoagulants, antiplatelet agents, and neurohormonal blockers are standard of care in the treatment of patients with AMI, given their established effects on morbidity and mortality. Drugs lowering low density lipoprotein (LDL) cholesterol, primarily hydroxyl-methylglutaryl-coA reductase inhibitors -statins -have been studied as a means not only to reduce LDL cholesterol (and hence the incidence of recurrent AMI), but also as an adjunct to acute AMI therapy to reduce the acute complications. In the MIRACL trial, atorvastatin 80 mg, administered within 24 to 96 hours after presentation with acute coronary syndrome (ACS), significantly reduced the composite endpoint of death, nonfatal AMI, cardiac arrest with resuscitation, or recurrent symptomatic myocardial infarction from 17.4% to 14.8% in the first 16 weeks when compared to placebo (relative risk = 0.84 [0.70 -1.00], p=0.048) [2].In the ARMYDA trial, high-dose atorvastatin for 7 days prior to elective percutaneous intervention (PCI) significantly reduced periprocedural myocardial infarction (MI) rates from 18% to 5% (p=0.025) [3]. This was followed by the ARMYDA-ACS trial, showing that initiation of high dose atorvstatin therapy in patients presenting with non-ST elevation ACS sent to early (<48 hours) angiography reduced the composite primary endpoint of death, MI, or target vessel revascularization from 17% to 5% compared to placebo (p=0.010) at 30 days [4].Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors are a promising new treatment strategy for LDL cholesterol lowering, demonstrating potent LDL lowering effects in addition to or compared to statins, in stable patients in primary or secondary prevention [5,6]. PCSK9 is predominantly produced in the liver, intestine, and kidney, where it is secreted into the plasma and binds the extracellular component of LDL receptors (LDL-R). Once bound, the LDLR-PCSK9 complex is internalized and directed it to the lysosome for degradation [7]. PCSK9 inhibitors have been formulated as monoclonal antibodies, designed to bind PCSK9 and prevent this series of events. As an effect, LDL-R concentrations on the surface of hepatocytes are increased, and more LDL is removed from the circulation. Two PCSK9 inhibitors, alirocumab (Praluent™) and evolocumab (Repatha™), are currently approved by the United States of America Food & Drug Administration for primary prevention in patients...

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“…16 Importantly, other mechanisms have been recognized that do not require scavenger receptor-mediated uptake of lipoproteins but also contribute to foam-cell formation, such as macropinocytosis of native LDL, macropinocytosis and phagocytosis of oxLDL and internalization of aggregated LDL (reviewed in ref. 17). Lipid-laden macrophages exhibit a reduced rate of exit from the lesion-either back to circulation or to the lymphatics-with a resultant increased lifespan in the subintima that only contributes to exacerbate the inflammatory response, induce smooth muscle cell proliferation and maintain the endothelium in an activated state with additional recruitment of circulating monocytes.…”

Section: Role Of Macrophages In Atherosclerosismentioning

confidence: 99%

“…Recent studies underscored a role of endothelial TRPC3 in inflammatory signaling and monocycle recruitment to coronary endothelium, 3,4 suggesting that this channel-and perhaps other members of the TRPC HDL. 17 In advanced lesions (stages IV-VI of the Stary classification 23 ), macrophages noticeably accumulate unesterified free cholesterol, which is a major triggering factor of endoplasmic reticulum (ER) stress. Persistent ER stress promotes apoptosis through the PERK, IRE-1α and ATF6 pathways.…”

Section: Role Of Macrophages In Atherosclerosismentioning

confidence: 99%