Abstract:
:Mononuclear phagocytes (MPs) relevant to atherosclerosis include monocytes, macrophages, and dendritic cells. A decade ago, studies on macrophage behavior in atherosclerotic lesions were often limited to quantification of total macrophage area in cross-sections of plaques. Although technological advances are still needed to examine plaque MP populations in an increasingly dynamic and informative manner, innovative methods to interrogate the biology of MPs in atherosclerotic plaques developed in the past few years point to several mechanisms that regulate the accumulation and function of MPs within plaques. Here, I review the evolution of atherosclerotic plaques with respect to changes in the MP compartment from the initiation of plaque to its progression and regression, discussing the roles that recruitment, proliferation, and retention of MPs play at these different disease stages. Additional work in the future will be needed to better distinguish macrophages and dendritic cells in plaque and to address some basic unknowns in the field, including just how cholesterol drives accumulation of macrophages in lesions to build plaques in the first place and how macrophages as major effectors of innate immunity work together with components of the adaptive immune response to drive atherosclerosis. Answers to these questions are sought with the goal in mind of reversing disease where it exists and preventing its development where it does not.
journal_name
Circ Resjournal_title
Circulation researchauthors
Randolph GJdoi
10.1161/CIRCRESAHA.114.301174subject
Has Abstractpub_date
2014-05-23 00:00:00pages
1757-71issue
11eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.114.301174journal_volume
114pub_type
杂志文章,评审abstract::Recent studies in isolated cardiac tissue preparations have demonstrated the applicability of a one-dimensional difference equation model describing the global behavior of a driven nonpacemaker cell to the understanding of rate-dependent cardiac excitation. As a first approximation to providing an ionic basis to compl...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.6.1510
更新日期:1990-12-01 00:00:00
abstract::Quinidine is the most commonly used drug for the chronic treatment of ventricular arrhythmias, but it may be arrhythmogenic. Much information exists concerning quinidine's effects on active properties in cardiac tissues, but virtually nothing is known of its effects on passive properties. We studied the effects of qui...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.2.244
更新日期:1987-08-01 00:00:00
abstract::Vasoactive drugs are known to affect impedance (pressure/flow) and vessel wall motion in arteries. The nonlinear theory of oscillatory flow in straight elastic vessels indicates that wall shear rate is affected by changes in impedance phase angle and wall motion. To test whether wall shear rate depends on impedance ph...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.4.637
更新日期:1994-10-01 00:00:00
abstract:RATIONALE:The dramatic upregulation of αvβ3-integrin that occurs in the vasculature during tumor growth has long suggested that the endothelial expression of this molecule is an ideal target for antiangiogenic therapy to treat cancer. This discovery led to the development of small-molecule inhibitors directed against α...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.301591
更新日期:2014-01-03 00:00:00
abstract::We have used tryptic digestion to determine whether Ca(2+) can regulate cardiac ryanodine receptor (RyR) channel gating from within the lumen of the sarcoplasmic reticulum (SR) or whether Ca(2+) must first flow through the channel and act via cytosolically located binding sites. Cardiac RyRs were incorporated into bil...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.3.201
更新日期:2000-08-04 00:00:00
abstract:RATIONALE:The mechanisms driving atherothrombotic risk in individuals with JAK2 V617F ( Jak2 VF) positive clonal hematopoiesis or myeloproliferative neoplasms are poorly understood. OBJECTIVE:The goal of this study was to assess atherosclerosis and underlying mechanisms in hypercholesterolemic mice with hematopoietic ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.313283
更新日期:2018-11-09 00:00:00
abstract::In studies that attempt to measure intracellular calcium [( Ca2+]i) in the intact heart with the calcium indicator indo 1-AM, a fundamental assumption is that the signals report changes in myocyte [Ca2+]i. We studied isolated perfused rabbit hearts loaded with the calcium probe indo 1-AM and recorded surface fluoresce...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.2.415
更新日期:1990-08-01 00:00:00
abstract::Controversy exists whether positive end-expiratory pressure (PEEP) ventilation lowers cardiac output by reducing left ventricular preload, or by a combination of mechanisms. Sixteen open-chest dogs were instrumented for measurement of left and right ventricular pressure, aortic flow, and left ventricular dimensions. W...
journal_title:Circulation research
pub_type: 杂志文章,收录出版
doi:10.1161/01.res.49.4.1017
更新日期:1981-10-01 00:00:00
abstract::Sixteen years ago, mutations in cardiac troponin (Tn)T and α-tropomyosin were linked to familial hypertrophic cardiomyopathy, thus transforming the disorder from a disease of the β-myosin heavy chain to a disease of the cardiac sarcomere. From the outset, studies suggested that mutations in the regulatory thin filamen...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.110.224170
更新日期:2011-03-18 00:00:00
abstract::The consequences of endothelin receptor activation were examined in atrial tumor myocytes derived from transgenic mice (AT-1 cells). Endothelin-1 (endothelin) stimulates phosphoinositide hydrolysis in a dose-dependent manner. Endothelin also induces the rapid and transient translocation of protein kinase C (PKC)-epsil...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.4.724
更新日期:1996-04-01 00:00:00
abstract::The mechanism of propranolol-inhibited sarcolemmal membrane lipid peroxidation was investigated by electron spin resonance spin-trapping technique using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2-methyl-2-nitrosopropane (MNP). Highly purified canine myocytic sarcolemma were peroxidized by a superoxide-driven (from ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.4.1151
更新日期:1989-10-01 00:00:00
abstract::Spatial and temporal organization of signal transduction is coordinated through the segregation of signaling enzymes in selected cellular compartments. This highly evolved regulatory mechanism ensures the activation of selected enzymes only in the vicinity of their target proteins. In this context, cAMP-responsive tri...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.262899
更新日期:2012-08-03 00:00:00
abstract::Hibernating myocardium, characterized by reductions in flow and function at rest, has limited contractile reserve in response to increases in external workload. We hypothesized that this attenuation of function reflects an adaptive downregulation that prevents the development of metabolic evidence of ischemia during s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000049104.57549.03
更新日期:2003-01-10 00:00:00
abstract:RATIONALE:Mitochondria are key integrators of convergent intracellular signaling pathways. Two important second messengers modulated by mitochondria are calcium and reactive oxygen species. To date, coherent mechanisms describing mitochondrial integration of calcium and oxidative signaling in arterial smooth muscle are...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.306996
更新日期:2015-12-04 00:00:00
abstract::Hemodynamic shear stress elicits a rise in endothelial [Ca2+]i, which may serve as a key second messenger to regulate many flow-associated physiological and biochemical processes. In the present study, we used Mn2+ quenching of fluorescent dye Fluo3 as an assay to investigate the Ca2+ influx of rat aortic endothelial ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000054625.24468.08
更新日期:2003-02-21 00:00:00
abstract::Previous studies have demonstrated a role for voltage-gated K+ (Kv) channel alpha subunits of the Kv4 subfamily in the generation of rapidly inactivating/recovering cardiac transient outward K+ current, I(to,f), channels. Biochemical studies suggest that mouse ventricular I(to,f) channels reflect the heteromeric assem...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000196559.63223.aa
更新日期:2005-12-09 00:00:00
abstract::Nuclear factor kappa B (NF-kappaB) participates in hypertension-induced vascular and target-organ damage. We tested whether or not endothelial cell-specific NF-kappaB suppression would be ameliorative. We generated Cre/lox transgenic mice with endothelial cell-restricted NF-kappaB super-repressor IkappaBalphaDeltaN (T...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.150474
更新日期:2007-08-03 00:00:00
abstract:RATIONALE:The vascular adventitia is a complex layer of the vessel wall consisting of vasa vasorum microvessels, nerves, fibroblasts, immune cells, and resident progenitor cells. Adventitial progenitors express the stem cell markers, Sca1 and CD34 (adventitial sca1-positive progenitor cells [AdvSca1]), have the potenti...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.309322
更新日期:2017-01-20 00:00:00
abstract::Postnatal development of the mammalian heart is associated with changes in the population of isoforms of the thin filament proteins. We correlated the change in thin filament proteins, which occur in rabbit hearts between 5 days and 22 days of age, with changes in Ca2+ dependence of myofibrillar ATPase activity, force...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1204
更新日期:1990-05-01 00:00:00
abstract::Platelet hyperactivity associated with hyperlipidemia may contribute to development of a prothrombotic state. We previously showed that oxidized low-density lipoprotein (oxLDL) formed in the setting of hyperlipidemia and atherosclerosis activated platelets in a CD36-dependent manner. We now show that mitogen-activated...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.172064
更新日期:2008-06-20 00:00:00
abstract::The remodeling of ventricular gap junctions, as defined by changes in size, distribution, or function, is a prominent feature of diseased myocardium. However, the regulation of assembly and maintenance of gap junctions remains poorly understood. To investigate N-cadherin function in the adult myocardium, we used a flo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000181132.11393.18
更新日期:2005-09-02 00:00:00
abstract::Electrical propagation in the normal heart occurs via intercellular transfer of current at gap junctions. Alterations in intercellular coupling in the diseased heart are critical in the pathogenesis of reentrant ventricular arrhythmias. Until recently only a single gap junction protein was known to couple cardiac myoc...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.2.438
更新日期:1992-02-01 00:00:00
abstract::Given the essential role played by gap junctions in the coordination of cardiac muscle contraction, it is plausible that down-regulation of gap junctional conduction is in part responsible for the contractile dysfunction observed in hypertrophied and failing hearts. In the present study, we analyzed the expression and...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.8.672
更新日期:1999-10-15 00:00:00
abstract::Isovolumic relaxation abnormalities have been noted in the ischemic left ventricle, but altered end-diastolic distensibility, as well as the role of right ventricular distention, is debated. Accordingly, left ventricular end-diastolic pressure and myocardial segment length were studied in the open-chest dogs with crit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.2.203
更新日期:1984-08-01 00:00:00
abstract::We studied product inhibition of the actin-activated ATPase of myosin subfragment-1 (S-1) from the three types of muscle tissue: skeletal, cardiac, and smooth. Increasing levels of [MgADP] in the 0-1-mM range caused significant inhibition of the actin-activated MgATPase activity of cardiac and gizzard but not skeletal...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.5.1067
更新日期:1992-11-01 00:00:00
abstract::Increased activity of matrix metalloproteinases (MMPs) has been implicated in numerous disease processes, including tumor growth and metastasis, arthritis, and periodontal disease. It is now becoming increasingly clear that extracellular matrix degradation by MMPs is also involved in the pathogenesis of cardiovascular...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/hh1501.094396
更新日期:2001-08-03 00:00:00
abstract::We tested the hypothesis that TNF-alpha induces early-onset endothelial adhesivity toward PMN by activating the constitutive endothelial cell surface ICAM-1, the beta2-integrin (CD11/CD18) counter-receptor. Stimulation of human pulmonary artery endothelial cells with TNF-alpha resulted in phosphorylation of ICAM-1 wit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000072971.88704.CB
更新日期:2003-05-30 00:00:00
abstract::Cardiac failure appears rapidly during severe hypoxia and precedes a substantial reduction in adenosine triphosphate content. Reduced adenosine triphosphate turnover, in the presence of nearly normal content, may be the metabolic basis for contractile failure during hypoxia. To measure both the myocardial content and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.6.871
更新日期:1987-06-01 00:00:00
abstract::A selective history of the pathophysiological, structural, and metabolic changes found during an episode of severe myocardial ischemia in the canine heart is presented. The changes that cause ischemic injury to become irreversible are discussed in detail because these changes are the target of any successful therapy d...
journal_title:Circulation research
pub_type: 历史文章,杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300987
更新日期:2013-08-02 00:00:00
abstract::Mechanisms of denervation supersensitivity to sympathomimetic amines were studied in conscious animals. Norepinephrine, 0.1 micrograms/kg, increased left ventricular dP/dt significantly more (4208 +/- 828 mm Hg/sec) in dogs with cardiac denervation than in intact dogs (1029 +/- 280 mm Hg/sec), P less than 0.01, wherea...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.1.55
更新日期:1985-07-01 00:00:00