Abstract:
BACKGROUND:Myocardium irreversibly injured by ischemic stress must be efficiently repaired to maintain tissue integrity and contractile performance. Macrophages play critical roles in this process. These cells transform across a spectrum of phenotypes to accomplish diverse functions ranging from mediating the initial inflammatory responses that clear damaged tissue to subsequent reparative functions that help rebuild replacement tissue. Although macrophage transformation is crucial to myocardial repair, events governing this transformation are poorly understood. METHODS:Here, we set out to determine whether innate immune responses triggered by cytoplasmic DNA play a role. RESULTS:We report that ischemic myocardial injury, along with the resulting release of nucleic acids, activates the recently described cyclic GMP-AMP synthase-stimulator of interferon genes pathway. Animals lacking cyclic GMP-AMP synthase display significantly improved early survival after myocardial infarction and diminished pathological remodeling, including ventricular rupture, enhanced angiogenesis, and preserved ventricular contractile function. Furthermore, cyclic GMP-AMP synthase loss of function abolishes the induction of key inflammatory programs such as inducible nitric oxide synthase and promotes the transformation of macrophages to a reparative phenotype, which results in enhanced repair and improved hemodynamic performance. CONCLUSIONS:These results reveal, for the first time, that the cytosolic DNA receptor cyclic GMP-AMP synthase functions during cardiac ischemia as a pattern recognition receptor in the sterile immune response. Furthermore, we report that this pathway governs macrophage transformation, thereby regulating postinjury cardiac repair. Because modulators of this pathway are currently in clinical use, our findings raise the prospect of new treatment options to combat ischemic heart disease and its progression to heart failure.
journal_name
Circulationjournal_title
Circulationauthors
Cao DJ,Schiattarella GG,Villalobos E,Jiang N,May HI,Li T,Chen ZJ,Gillette TG,Hill JAdoi
10.1161/CIRCULATIONAHA.117.031046subject
Has Abstractpub_date
2018-06-12 00:00:00pages
2613-2634issue
24eissn
0009-7322issn
1524-4539pii
CIRCULATIONAHA.117.031046journal_volume
137pub_type
杂志文章相关文献
CIRCULATION文献大全abstract:BACKGROUND:Optical mapping of cytosolic calcium transients in intact mammalian hearts is now possible using long-wavelength [Ca(2+)](i) indicators. We propose that beat-to-beat [Ca(2+)](i) transient alternans during ischemia may lead to spatial and temporal heterogeneity of calcium-activated membrane currents. METHODS...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc4201.097136
更新日期:2001-10-23 00:00:00
abstract:BACKGROUND:Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in pati...
journal_title:Circulation
pub_type: 杂志文章,随机对照试验
doi:10.1161/CIRCULATIONAHA.113.001458
更新日期:2013-07-30 00:00:00
abstract::Valve-related complications after Björk-Shiley mitral valve implantation (n = 475), aortic valve implantation (n = 424), or mitral-aortic valve implantation (n = 119) were compared with those after St. Jude Medical mitral valve replacement (n = 173), aortic valve replacement (n = 152), or mitral-aortic valve replaceme...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::Echocardiographic and cardiac catheterization findings were compared in 61 patients with mitral stenosis without other significant lesions in an attempt to determine the clinical usefulness of echocardiography in the assessment of such patients. There was a poor correlation between the E-F slope on the echocardiogram ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.52.4.664
更新日期:1975-10-01 00:00:00
abstract:BACKGROUND:Glycosphingolipids, integral components of the cell membrane, have been shown to serve as messengers, transducing growth factor-initiated phenotypes. Here, we have examined whether inhibition of glycosphingolipid synthesis could ameliorate atherosclerosis and arterial stiffness in transgenic mice and rabbits...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.113.007559
更新日期:2014-06-10 00:00:00
abstract:BACKGROUND:High-altitude pulmonary edema (HAPE) is characterized by pulmonary hypertension, increased pulmonary capillary permeability, and hypoxemia. Treatment is limited to descent to lower altitude and administration of oxygen. METHODS AND RESULTS:We studied the acute effects of inhaled nitric oxide (NO), 50% oxyge...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.98.22.2441
更新日期:1998-12-01 00:00:00
abstract:BACKGROUND:In individuals without known cardiovascular disease, elevated body mass index (BMI) (weight/height2) is associated with an increased risk of death. However, in patients with certain specific chronic diseases, including heart failure, low BMI has been associated with increased mortality. METHODS AND RESULTS:...
journal_title:Circulation
pub_type: 杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.106.679779
更新日期:2007-08-07 00:00:00
abstract:BACKGROUND:Adults with obesity or type 2 diabetes mellitus (T2DM) are at higher risk for stroke and myocardial infarction. Increased carotid intima-media thickness (cIMT) and stiffness are associated with these adverse outcomes. We compared carotid arteries in youth who were lean, were obese, or had T2DM. METHODS AND ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.830380
更新日期:2009-06-09 00:00:00
abstract:BACKGROUND:In subjects of all ages, those who weigh the most often have the highest blood pressure. Thus, in epidemiological studies, weight is the most important correlate of blood pressure. Using the data from the Medical College of Virginia Twin Study, we asked these questions: 1) Do the same genetic paths that regu...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.86.6.1780
更新日期:1992-12-01 00:00:00
abstract:BACKGROUND:Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) has been used to measure T2* changes in skeletal muscle tissue of healthy volunteers. The BOLD effect is assumed to primarily reflect changes in blood oxygenation at the tissue level. We compared the calf muscle BOLD response of patien...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.605717
更新日期:2006-06-27 00:00:00
abstract:BACKGROUND:The age association of cardiovascular disease may be in part because its metabolic risk factors tend to rise with age. Few studies have analyzed age associations of multiple metabolic risks in the same population, especially in nationally representative samples. We examined worldwide variations in the age as...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.111.058834
更新日期:2012-05-08 00:00:00
abstract:BACKGROUND:The possible contribution of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, to neurohumoral compensation for hemodynamic stress was examined in nine normal volunteers and six patients with severe congestive heart failure. METHODS AND RESULTS:Plasma levels of endothelin-1 were measured w...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.85.2.510
更新日期:1992-02-01 00:00:00
abstract:BACKGROUND:Depressed ventricular performance and neurohormonal activation are key pathophysiological features of congestive heart failure (CHF). Although angiotensin-converting enzyme inhibitors and beta-adrenoceptor blockers exert beneficial effects in CHF, mortality remains unacceptably high, and the development of f...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/01.cir.103.19.2336
更新日期:2001-05-15 00:00:00
abstract::The clinical use of citrate-phosphate-dextrose during blood-product transfusion is known to affect ionized calcium levels and can result in depression of myocardial contractility. The immature heart appears to have an intrinsic reduction in contractile state compared with the adult heart and may be more dependent on t...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract::Electrophysiologic effects of 50 mg iv ajmaline were evaluated in 10 patients with atrioventricular nodal reentrant paroxysmal supraventricular tachycardia (PSVT) utilizing the slow pathway for antegrade and the fast pathway for retrograde conduction. Ajmaline terminated the PSVT in all 10 patients in 17 to 165 sec (m...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.70.5.876
更新日期:1984-11-01 00:00:00
abstract:BACKGROUND:Thrombolytic therapy is a promising alternative to valve replacement in the management of prosthetic valve thrombosis. We sought to determine the short- and long-term results of treating thrombosed St. Jude heart valves with thrombolytic therapy as the primary treatment modality. METHODS AND RESULTS:Between...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.87.1.30
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND:Hypothermic hyperkalemic cardioplegia results in significant myocyte swelling and impaired contractility. These detrimental effects may be eliminated by the addition of an adenosine triphosphate-sensitive potassium (KATP) channel opener. This study evaluated the hypothesis that a KATP channel opener (diazoxi...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.104.523746
更新日期:2005-08-30 00:00:00
abstract:BACKGROUND:Coronary heart disease (CHD) represents the largest share of cardiovascular disease in the United States, but there are conspicuous discrepancies between CHD and total cardiovascular death rates across the states, possibly due in part to variations in physician assignment of causes of death. Our aim was to i...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.595777
更新日期:2006-05-02 00:00:00
abstract::In three newborn infants with infradiaphragmatic total anomalous pulmonary venous connection, the common pulmonary vein was visualized with two-dimensional echocardiography and validated with saline contrast injections. The transducer was placed in the subcostal region in a sagittal body plane so as to image the desce...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.66.5.1129
更新日期:1982-11-01 00:00:00
abstract:BACKGROUND:Although global ischemia induces troponin I (TnI) degradation, regional ischemia does not. We hypothesized that this disparity is related to preload-induced proteolysis, which varies as a function of the amount of myocardium at risk of ischemia. METHODS AND RESULTS:Isolated rat hearts were buffer-perfused a...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.103.16.2035
更新日期:2001-04-24 00:00:00
abstract:BACKGROUND:Paroxysmal atrial fibrillation (AF) naturally progresses toward chronic AF at an estimated rate of 15% to 30% over a 1- to 3-year period. Pulmonary vein (PV) isolation is increasingly performed for the treatment of drug-refractory paroxysmal AF. The long-term data on clinical outcome after circumferential PV...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.110.946806
更新日期:2010-12-07 00:00:00
abstract:BACKGROUND:Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events. METHODS:In 3281 participants (45-74 years of age), free from cardiovascul...
journal_title:Circulation
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.116.027034
更新日期:2018-02-13 00:00:00
abstract:BACKGROUND:Current information on the epidemiology and outcomes of hypertrophic cardiomyopathy (HCM) in children is limited by disease diversity and small case series. METHODS AND RESULTS:The Pediatric Cardiomyopathy Registry has collected prospective and retrospective data on children diagnosed with HCM since 1990. W...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.106.621185
更新日期:2007-02-13 00:00:00
abstract:BACKGROUND:The heart can synthesize epinephrine. Homogenates of rat heart, which contain the enzymes phenylethanolamine N-methyltransferase (PNMT) and nonspecific N-methyltransferase (NMT), methylate norepinephrine to form epinephrine. The cardiac atrium contains primarily PNMT and the cardiac ventricle contains both P...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.84.2.891
更新日期:1991-08-01 00:00:00
abstract::Twenty-two patients who underwent anatomic correction of transposition of the great arteries at the arterial level at the age of 8 weeks to 14 years were reinvestigated 1-4.6 years (mean 2.0 years) after operation. A Dacron tube was used to bridge the gap between the proximal pulmonary route and the distal pulmonary a...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1982-08-01 00:00:00
abstract::The importance of pulmonary artery size and the value of a standardized pulmonary artery index (PAI) in predicting outcome after Fontan's repair have previously been reported and questioned. We retrospectively reviewed 29 patients undergoing modified Fontan repair at The Children's Hospital of Philadelphia to examine ...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::Although thrombolytic therapy has been a major advance in the treatment of acute myocardial infarction, in at least 25% of patients the artery remains occluded after administration. In these patients, the strategy of "rescue" or "salvage" angioplasty is frequently used although follow-up data are limited. Sixty-three ...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract:BACKGROUND:Angiotensin-converting enzyme (ACE) inhibition potentiates the tissue-type plasminogen activator (t-PA) response to exogenous bradykinin. This study tested the hypothesis that ACE inhibition increases endothelial t-PA release through endogenous bradykinin. METHODS AND RESULTS:We measured the effect of intra...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.0000046268.59922.a4
更新日期:2003-02-04 00:00:00
abstract:BACKGROUND:Cardiopulmonary bypass and cardiac surgery are associated with a significant systemic inflammatory response that may increase postoperative complications. This meta-analysis assessed whether the benefits and risks of corticosteroid use were dose dependent in adult cardiac surgery. METHODS AND RESULTS:Random...
journal_title:Circulation
pub_type: 杂志文章,meta分析
doi:10.1161/CIRCULATIONAHA.108.848218
更新日期:2009-04-14 00:00:00
abstract::The morphologic consequences of transluminal angioplasty of stenotic atherosclerotic coronary arteries are unknown. This study describes the production of aortoiliac atherosclerosis in rabbits and reports the morphologic changes after transluminal angioplasty of stenotic arterial lesions. Atherosclerotic lesions were ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.61.4.778
更新日期:1980-04-01 00:00:00