Abstract:
:The introduction of statins ≈ 30 years ago ushered in the era of lipid lowering as the most effective way to reduce risk of atherosclerotic cardiovascular disease. Nonetheless, residual risk remains high, and statin intolerance is frequently encountered in clinical practice. After a long dry period, the field of therapeutics targeted to lipids and atherosclerosis has entered a renaissance. Moreover, the demonstration of clinical benefits from the addition of ezetimibe to statin therapy in subjects with acute coronary syndromes has renewed the enthusiasm for the cholesterol hypothesis and the hope that additional agents that lower low-density lipoprotein will decrease risk of atherosclerotic cardiovascular disease. Drugs in the orphan disease category are now available for patients with the most extreme hypercholesterolemia. Furthermore, discovery and rapid translation of a novel biological pathway has given rise to a new class of cholesterol-lowering drugs, the proprotein convertase subtilisin kexin-9 inhibitors. Trials of niacin added to statin have failed to demonstrate cardiac benefits, and 3 cholesterol ester transfer protein inhibitors have also failed to reduce atherosclerotic cardiovascular disease risk, despite producing substantial increases in HDL levels. Although the utility of triglyceride-lowering therapies remains uncertain, 2 large clinical trials are testing the influence of omega-3 polyunsaturated fatty acids on atherosclerotic events in hypertriglyceridemia. Novel antisense therapies targeting apolipoprotein C-III (for triglyceride reduction) and apo(a) (for lipoprotein(a) reduction) are showing a promising trajectory. Finally, 2 large clinical trials are formally putting the inflammatory hypothesis of atherosclerosis to the test and may open a new avenue for cardiovascular disease risk reduction.
journal_name
Circ Resjournal_title
Circulation researchauthors
Shapiro MD,Fazio Sdoi
10.1161/CIRCRESAHA.115.306471subject
Has Abstractpub_date
2016-02-19 00:00:00pages
732-49issue
4eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.115.306471journal_volume
118pub_type
杂志文章,评审abstract::Bradykinin relaxes arterioles on the brain's surface. This response is endothelium-dependent. The data presented here confirm the hypothesis that hydroxyl free radical mediates this response and may be the endothelium-dependent relaxing factor for bradykinin in this microvascular bed. The response to a locally applied...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.4.601
更新日期:1987-10-01 00:00:00
abstract::A mathematical model for the regulation of mechanical activity in cardiac muscle has been developed based on a three-element rheological model of this muscle. The contractile element has been modeled taking into account the results of extensive mechanical tests that involved the recording of length-force and force-vel...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.5.1171
更新日期:1991-11-01 00:00:00
abstract:RATIONALE:Although PSA (prostate-specific antigen)-a tumor marker for prostate cancer-has been reported to be associated with cardiovascular disease (CVD) risk factors, studies on the association of PSA with subclinical and clinical CVD remain limited. OBJECTIVE:We examined the association of total serum PSA within th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.313413
更新日期:2019-05-10 00:00:00
abstract::We investigated the combined effectiveness of intra-aortic balloon counterpulsation and hyperosmotic mannitol (25%) on regional myocardial blood flow during acute coronary insufficiency. Cardiac output and paced heart rate were held constant in chloralose-anesthetized dogs during right heart bypass. Acute coronary ins...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.38.6.506
更新日期:1976-06-01 00:00:00
abstract::A new protocol has been developed for selective removal of the endothelium from the arteries of the perfused rat hind-limb preparation. The hind limb was perfused with oxygenated Krebs-Ringer bicarbonate solution with a combination of high flow and timed air bubbles (2 minutes at high flow followed by 5 minutes of air...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.6.1190
更新日期:1989-06-01 00:00:00
abstract::Recent studies from our laboratory involving syncytial preparations have delineated electrophysiological distinctions between epicardium, endocardium, and a unique population of cells in the deep subepicardial to midmyocardial layers (M region) of the canine ventricle. In the present study, we used standard microelect...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.3.671
更新日期:1993-03-01 00:00:00
abstract::Increased levels of C-peptide, a cleavage product of proinsulin, circulate in patients with insulin resistance and early type 2 diabetes mellitus. Recent data suggest a potential causal role of C-peptide in atherogenesis by promoting monocyte and T-lymphocyte recruitment into the vessel wall. The present study examine...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000251231.16993.88
更新日期:2006-11-24 00:00:00
abstract::Cardiac hemodynamics, diameter, blood flow velocity, and volumic flow of the brachial artery were studied before and after diltiazem administration in 11 patients with sustained essential hypertension. The study was compared with the hemodynamic effects of dihydralazine. The caliber of the brachial artery was evaluate...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract::Mitochondrial quality is a crucial determinant of cell viability, and mitochondrial autophagy plays a central role in this control mechanism. Based on studies in yeast, numerous investigations of this process have been conducted, and the framework of mammalian mitochondrial autophagy is progressively appearing. Howeve...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.303790
更新日期:2015-04-10 00:00:00
abstract::We recorded 60 DC simultaneous electrograms from isolated porcine and canine hearts in the first minutes after coronary occlusion. Ventricular premature beats (VPB) originated from the normal side of the ischemic border, which was frequently separated from the central ischemic area showing delayed activity by a small ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.50.4.527
更新日期:1982-04-01 00:00:00
abstract::The alpha-adrenergic blocking drugs, phentolamine and Hydergine, both act centrally at different sites to depress and enhance the pressor and sympathetic nerve response to decreased baroreceptor afferent input in anesthetized cats. Depression of the rise in blood pressure and sympathetic nerve discharge during bilater...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.5.724
更新日期:1976-11-01 00:00:00
abstract::Current management of ventricular septal defect (VSD) after myocardial infarction (MI) is aimed at improving left ventricular (LV) performance by afterload reduction as a means of hemodynamic stabilization or shunt control. The current investigation was undertaken to determine whether primary manipulation of right ven...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.40.4.372
更新日期:1977-04-01 00:00:00
abstract::During an investigation of the effect of ryanodine on contractions in cardiac muscle, it was found that long rest periods removed all or most of the drug's effect. Therefore, we studied the kinetics of block development and recovery from block produced by low concentrations of ryanodine (1-100 pM) on the postrest cont...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.4.560
更新日期:1987-04-01 00:00:00
abstract::The interaction between inflammatory cytokines and endothelial cells is a critical step in atherogenesis leading to endothelial dysfunction and inflammation. We have previously reported that the tumor necrosis factor superfamily member LIGHT could be involved in atherogenesis through its ability to promote vascular in...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.188078
更新日期:2009-01-02 00:00:00
abstract::Endothelins exert potent excitatory cardiac effects by acting on specific receptors on myocytes. In this study, we have examined the signal transduction mechanism for the chronotropic effect of endothelins in guinea pig atria. A competition binding of [125I]endothelin 1 ([125I]ET-1) using the recently developed ETA re...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.2.284
更新日期:1995-02-01 00:00:00
abstract:RATIONALE:Vascular endothelial growth factor (VEGF) affects angiogenesis, atherosclerosis, and cancer. Although the heritability of circulating VEGF levels is high, little is known about its genetic underpinnings. OBJECTIVE:Our aim was to identify genetic variants associated with circulating VEGF levels, using an unbi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.243790
更新日期:2011-08-19 00:00:00
abstract::G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane receptors, causing receptor uncoupling from G proteins and potentially activating non-G-protein signaling pathways. GRK2 is unique among members of the GRK family in that its genetic ablation causes embryonic le...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000247932.71270.2c
更新日期:2006-10-27 00:00:00
abstract::We examined the late coronary vascular response to carotid chemoreceptor reflex activation in normal, conscious dogs instrumented for the measurement of right main and left circumflex coronary artery blood flows, arterial and right ventricular pressures, and arterial and coronary sinus blood gases and O2 contents. Wit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.54.1.96
更新日期:1984-01-01 00:00:00
abstract::Cardiovascular aging is associated with decreased endothelial vasoreactivity and prolonged diastolic relaxation. As diminished NO signaling contributes to age-associated endothelial dysfunction, we tested the hypothesis that impaired NO signaling or bioactivity also contributes to slowed ventricular relaxation with ag...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.88.1.97
更新日期:2001-01-19 00:00:00
abstract::Brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are novel natriuretic peptides, originally isolated from porcine brain. Similar to atrial natriuretic peptide (ANP), BNP is also synthesized in and secreted from cardiocytes, but CNP is not expressed at significant levels in normal adult myocardium. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.1.9
更新日期:1992-07-01 00:00:00
abstract::We determined the effects of changing the spatial dispersion of acetylcholine release on the phase-dependent chronotropic responses to vagal stimulation in anesthetized dogs. We stimulated the vagus nerves with one brief burst of electrical pulses each cardiac cycle, and we changed the timing of the stimulus by a smal...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.4.844
更新日期:1990-10-01 00:00:00
abstract::Connexins have been hypothesized to play an important role in intercellular communication within the vascular wall and may provide a mechanistic explanation for conduction of vasomotor responses. To test this hypothesis, we studied the transmission of vasomotor responses in the intact skeletal muscle microcirculation ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.6.649
更新日期:2000-03-31 00:00:00
abstract::Inwardly rectifying K+ (Kir) channels are responsible for maintaining endothelial membrane potential and play a key role in endothelium-dependent vasorelaxation. In this study, we show that endothelial Kir channels are suppressed by hypercholesterolemic levels of lipoproteins in vitro and by serum hypercholesterolemia...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000218776.87842.43
更新日期:2006-04-28 00:00:00
abstract:RATIONALE:Human heregulins, neuregulin-1 type I polypeptides that activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, are expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester accumula...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.193870
更新日期:2009-08-28 00:00:00
abstract::We tested a number of hypotheses concerning the mechanism of K+-induced vasodilation of the coronary vascular bed. Blood flow in the circumflex artery was measured in pentobarbital-anesthetized, open-chest dogs. Intracircumflex artery bolus injections of 40 mumol of isomotic KCl produced decreases in coronary vascular...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.42.1.35
更新日期:1978-01-01 00:00:00
abstract::We have observed that acute medial cell loss is an initial event in the response to vascular injury induced by balloon-catheter distention of the rabbit carotid artery. Numerous apoptotic medial cells were observed as early as 30 minutes after balloon inflation, and a 70% loss of cellularity was evident by 90 minutes....
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.1.113
更新日期:1999-01-08 00:00:00
abstract::The activity of the adrenergic system plays an important role in the genesis of malignant arrhythmias and the spreading of the infarcted zone in acute myocardial ischemia. Acute myocardial ischemia induces an increased activity of adenylyl cyclase. This sensitization at the enzyme level as shown in the isolated perfus...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.6.1304
更新日期:1992-06-01 00:00:00
abstract::Many forms of vascular disease are characterized by increased transforming growth factor (TGF)-beta1 expression and endothelial dysfunction. Smad proteins are a key step in TGF-beta-initiated signal transduction. We hypothesized that NO may regulate endothelial TGF-beta-dependent gene expression. We show that NO inhib...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000191538.76771.66
更新日期:2005-11-25 00:00:00
abstract::Diabetes mellitus has profound adverse effects on vascular and, in particular, endothelial function. Although pressure-induced constriction ("myogenic tone") is a major contributor to the regulation of blood flow, little is known about the effects of diabetes on this response. Diabetes has been shown to diminish the d...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.6.996
更新日期:1997-12-01 00:00:00
abstract::The migration of medial smooth muscle cells (SMCs) into the intima is proposed to be an important process of intimal thickening in atherosclerotic lesions. The present study examined the possible effect of a novel endothelium-derived relaxing peptide, C-type natriuretic peptide (CNP), on oxidized low-density lipoprote...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.4.585
更新日期:1997-10-01 00:00:00