Abstract:
:Genome-wide association studies have provided a rich collection of ≈ 58 coronary artery disease (CAD) loci that suggest the existence of previously unsuspected new biology relevant to atherosclerosis. However, these studies only identify genomic loci associated with CAD, and many questions remain even after a genomic locus is definitively implicated, including the nature of the causal variant(s) and the causal gene(s), as well as the directionality of effect. There are several tools that can be used for investigation of the functional genomics of these loci, and progress has been made on a limited number of novel CAD loci. New biology regarding atherosclerosis and CAD will be learned through the functional genomics of these loci, and the hope is that at least some of these new pathways relevant to CAD pathogenesis will yield new therapeutic targets for the prevention and treatment of CAD.
journal_name
Circ Resjournal_title
Circulation researchauthors
Nurnberg ST,Zhang H,Hand NJ,Bauer RC,Saleheen D,Reilly MP,Rader DJdoi
10.1161/CIRCRESAHA.115.306464subject
Has Abstractpub_date
2016-02-19 00:00:00pages
586-606issue
4eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.115.306464journal_volume
118pub_type
杂志文章,评审abstract:RATIONALE:7-Ketocholesterol (7-KC), a form of cholesterol oxidation product, plays an essential role in the atherogenesis in animal models. OBJECTIVE:We sought to determine the association of circulating 7-KC with clinical cardiovascular outcomes and total mortality in patients with stable coronary artery disease. ME...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.311049
更新日期:2017-05-12 00:00:00
abstract::Chronic hypoxic pulmonary hypertension is associated with profound vascular remodeling and alterations in Ca(2+) homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Recent studies show that transient receptor potential (TRPC) genes, which encode store-operated and receptor-operated cation channels, play im...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000138952.16382.ad
更新日期:2004-09-03 00:00:00
abstract:RATIONALE:Inactivating mutations in the Forkhead Box transcription factor F1 (FOXF1) gene locus are frequently found in patients with alveolar capillary dysplasia with misalignment of pulmonary veins, a lethal congenital disorder, which is characterized by severe abnormalities in the respiratory, cardiovascular, and ga...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.304382
更新日期:2014-09-26 00:00:00
abstract:RATIONALE:Hydrogen peroxide (H(2)O(2)) serves as a key endothelium-derived hyperpolarizing factor mediating flow-induced dilation in human coronary arterioles (HCAs). The precise mechanisms by which H(2)O(2) elicits smooth muscle hyperpolarization are not well understood. An important mode of action of H(2)O(2) involve...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.258871
更新日期:2012-02-03 00:00:00
abstract::The myocardium contains collagen matrix that is a major determinant of its architecture, structural integrity, and mechanical properties. This fibrillar matrix consists primarily of type I and type III collagens having epimysial, perimysial, and endomysial components. The present study shows the alteration of collagen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.6.1474
更新日期:1990-12-01 00:00:00
abstract::Two gap junction proteins, connexin43 (Cx43) and connexin45 (Cx45), are coexpressed in many cardiac and other cells. Homomeric channels formed by these proteins differ in unitary conductance, permeability, and regulation. We sought to determine the ability of Cx43 and Cx45 to oligomerize with each other to form hetero...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000019580.64013.31
更新日期:2002-05-31 00:00:00
abstract::The precise, temporal order of gene expression during development is critical to ensure proper lineage commitment, cell fate determination, and ultimately, organogenesis. Epigenetic regulation of chromatin structure is fundamental to the activation or repression of genes during embryonic development. In recent years, ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.115.301517
更新日期:2014-07-07 00:00:00
abstract::Compelling evidence continues to emerge suggesting that the glycocalyx surface layer on vascular endothelial cells plays a determining role in numerous physiological processes including inflammation, microvascular permeability, and endothelial mechanotransduction. Previous research has shown that enzymes degrade the g...
journal_title:Circulation research
pub_type: 评论,杂志文章
doi:10.1161/CIRCRESAHA.108.191585
更新日期:2009-06-05 00:00:00
abstract::Smaller Ca2+ transients and systolic dysfunction in heart failure (HF) can be largely explained by reduced total sarcoplasmic reticulum (SR) Ca2+ content ([Ca]SRT). However, it is unknown whether low [Ca]SRT is manifest as reduced: (1) intra-SR free [Ca2+] ([Ca2+]SR), (2) intra-SR Ca2+ buffering, or (3) SR volume (as ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.152140
更新日期:2007-10-12 00:00:00
abstract::An animal model was used to test the hypothesis that in heart failure the decrease in the ability to resynthesize ATP through the creatine kinase (CK) reaction (which we call energy reserve) contributes to the inability of the heart to maintain its normal function and contractile reserve. One-week-old turkey poults we...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.5.893
更新日期:1996-05-01 00:00:00
abstract::Transgenic mice overexpressing the calcium binding protein, S100A4/Mts1, occasionally develop severe pulmonary vascular obstructive disease. To understand what underlies this propensity, we compared the pulmonary vascular hemodynamic and structural features of S100A4/Mts1 with control C57Bl/6 mice at baseline, followi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000182425.49768.8a
更新日期:2005-09-16 00:00:00
abstract::Volume expansion has been shown to increase plasma atrial natriuretic peptide (ANP) levels, but the precise role of paracrine and autocrine factors in stretch-induced cardiac hormone release is not clear. In the present study, we report the effects of endothelin (ET) and angiotensin receptor (AT receptor) antagonists ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.1.114
更新日期:1997-01-01 00:00:00
abstract::Ischemia/reperfusion (I/R) affects the integrity of the endoplasmic reticulum (ER), the site of synthesis and folding of numerous proteins. Therefore, I/R may activate the unfolded protein response (UPR), resulting in the induction of a collection of ER stress proteins, many of which are protective and function to res...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000220643.65941.8d
更新日期:2006-05-12 00:00:00
abstract::The transcription factor nuclear factor-kappaB (NF-kappaB) plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes involved in endothelial activation. Although recent reports have documented the contribution of NF-kappaB to apoptosis, it is still controversial. Especially, the r...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.9.974
更新日期:2000-05-12 00:00:00
abstract:RATIONALE:We previously reported that type VI collagen deposition increases in the infarcted myocardium in vivo. To date, a specific role for this nonfibrillar collagen has not been explored in the setting of myocardial infarction (MI). OBJECTIVE:To determine whether deletion of type VI collagen in an in vivo model of...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.252734
更新日期:2012-03-16 00:00:00
abstract::The contribution of centrally originating sympathetic activity to the myocardial extracellular accumulation of noradrenaline during the early phase of ischemia has been assessed in a perfused (Langendorff) rat heart preparation isolated except for its sympathetic innervation. A 10-minute electrical stimulation (4 Hz, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.5.702
更新日期:1984-11-01 00:00:00
abstract::After cervical aortic nerve section, mean arterial pressure in the unanesthetized dog increased by an average of 7.4 mm Hg. Following a more extensive denervation of aortic arch receptors by section of intrathoracic vagal branches, arterial pressure increased by 16.7 mm Hg. The above changes were seen in the stable st...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.1.26
更新日期:1979-07-01 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:RATIONALE:Smooth muscle precursor cells have previously been reported to reside in bone marrow and in the circulation, but little is currently known regarding the proximate stimuli for smooth muscle cell differentiation of these putative progenitors. OBJECTIVE:Because local thrombin generation occurs as an initial res...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.199984
更新日期:2009-07-31 00:00:00
abstract::Net cellular L-lactate efflux associated with accelerated anaerobic glycolysis has been implicated as a potential cause of the marked cellular K+ loss contributing to lethal cardiac arrhythmias in ischemic heart and to impaired function of fatigued skeletal muscle. To examine the mechanisms of transsarcolemmal L-lacta...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.5.829
更新日期:1994-05-01 00:00:00
abstract::We tested the hypothesis that accumulation of H+ or inorganic phosphate (Pi) is responsible for the early contractile failure of hypoxia by measuring maximal Ca2+-activated pressure and 31P nuclear magnetic resonance spectra in Langendorff-perfused ferret hearts at 30 degrees C. Maximal Ca2+-activated pressure was ide...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.59.3.270
更新日期:1986-09-01 00:00:00
abstract::Telomeres-the specialized DNA-protein structures at the ends of eukaryotic chromosomes-are essential for maintaining genome stability and integrity and for extended proliferative life span in both cultured cells and in the whole organism. Telomerase and additional telomere-associated proteins are necessary for preserv...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000122141.18795.9C
更新日期:2004-03-19 00:00:00
abstract::In a freshly isolated endothelial cell preparation from rabbit aorta, the regulation of the acetylcholine (ACh)-sensitive intracellular Ca2+ store and the effects of the Ca(2+)-induced Ca2+ release agonists ryanodine and caffeine were studied using fura 2 imaging fluorescence microscopy. ACh (10 mumol/L) caused a tran...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.1.37
更新日期:1995-07-01 00:00:00
abstract::To determine whether coronary vasodilator reserve that persists during myocardial ischemia is present in all left ventricular regions, we measured regional blood flow in 192 left ventricular pieces (mean weight, 201 mg) in each of eight dogs by using radioactive microspheres while perfusing the left main coronary arte...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.2.253
更新日期:1990-08-01 00:00:00
abstract::Increasing attention is currently devoted to the multiple roles that pericytes (also defined as mural, Rouget, or perivascular cells) may play during angiogenesis, vascular homeostasis, and pathology. Many recent excellent reviews thoroughly address these topics (see below); hence, we will not discuss them in detail h...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300203
更新日期:2013-07-19 00:00:00
abstract::Calcific aortic valve sclerosis involves inflammatory processes and occurs preferentially on the aortic side of endothelialized valve leaflets. Although the endothelium is recognized to play critical roles in focal vascular sclerosis, the contributions of valvular endothelial phenotypes to aortic valve sclerosis and s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000161998.92009.64
更新日期:2005-04-15 00:00:00
abstract::We studied the effects of intense sympathetic stimulation on the chronotropic responses of the heart to subsequent test stimulations of the cardiac autonomic nerves in dogs anesthetized with alpha-chloralose. Such intense sympathetic stimulations (which we refer to as "release stimulations") are known to release neuro...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.1.137
更新日期:1993-01-01 00:00:00
abstract::Endothelial cells, either in vivo or freshly isolated, respond when exposed to muscarinic agonists with an increase in cytosolic free calcium concentration ([Ca2+]i) and release of endothelium-derived relaxing factor (EDRF). When placed in culture, however, endothelial cells rapidly lose these responses, which may be ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.2.234
更新日期:1992-02-01 00:00:00
abstract::Oxygen free radicals have the ability to oxidize cholesterol. However, nothing is known about the effects of cholesterol oxidation on ion transport in isolated myocardial membranes. The purpose of the present study was to investigate the effects of in situ oxidative modification of sarcolemmal cholesterol on Ca2+ flux...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.1.18
更新日期:1991-01-01 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