The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis.

Abstract:

:In adult mammals, massive sudden loss of cardiomyocytes after infarction overwhelms the limited regenerative capacity of the myocardium, resulting in the formation of a collagen-based scar. Necrotic cells release danger signals, activating innate immune pathways and triggering an intense inflammatory response. Stimulation of toll-like receptor signaling and complement activation induces expression of proinflammatory cytokines (such as interleukin-1 and tumor necrosis factor-α) and chemokines (such as monocyte chemoattractant protein-1/ chemokine (C-C motif) ligand 2 [CCL2]). Inflammatory signals promote adhesive interactions between leukocytes and endothelial cells, leading to extravasation of neutrophils and monocytes. As infiltrating leukocytes clear the infarct from dead cells, mediators repressing inflammation are released, and anti-inflammatory mononuclear cell subsets predominate. Suppression of the inflammatory response is associated with activation of reparative cells. Fibroblasts proliferate, undergo myofibroblast transdifferentiation, and deposit large amounts of extracellular matrix proteins maintaining the structural integrity of the infarcted ventricle. The renin-angiotensin-aldosterone system and members of the transforming growth factor-β family play an important role in activation of infarct myofibroblasts. Maturation of the scar follows, as a network of cross-linked collagenous matrix is formed and granulation tissue cells become apoptotic. This review discusses the cellular effectors and molecular signals regulating the inflammatory and reparative response after myocardial infarction. Dysregulation of immune pathways, impaired suppression of postinfarction inflammation, perturbed spatial containment of the inflammatory response, and overactive fibrosis may cause adverse remodeling in patients with infarction contributing to the pathogenesis of heart failure. Therapeutic modulation of the inflammatory and reparative response may hold promise for the prevention of postinfarction heart failure.

journal_name

Circ Res

journal_title

Circulation research

authors

Prabhu SD,Frangogiannis NG

doi

10.1161/CIRCRESAHA.116.303577

subject

Has Abstract

pub_date

2016-06-24 00:00:00

pages

91-112

issue

1

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.116.303577

journal_volume

119

pub_type

杂志文章,评审
  • Randomized controlled trials of blood pressure lowering in hypertension: a critical reappraisal.

    abstract::Sixty-eight blood pressure (BP)-lowering randomized controlled trials (defined as randomized controlled trials comparing active treatment with placebo, or less active treatment, achieving a BP difference, performed between 1966 and end 2013 in cohorts with ≥ 40% hypertensive patients, and exclusive of trials in acute ...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.116.303641

    authors: Zanchetti A,Thomopoulos C,Parati G

    更新日期:2015-03-13 00:00:00

  • Uncoupling protein 2 impacts endothelial phenotype via p53-mediated control of mitochondrial dynamics.

    abstract:RATIONALE:Mitochondria, although required for cellular ATP production, are also known to have other important functions that may include modulating cellular responses to environmental stimuli. However, the mechanisms whereby mitochondria impact cellular phenotype are not yet clear. OBJECTIVE:To determine how mitochond...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.113.301319

    authors: Shimasaki Y,Pan N,Messina LM,Li C,Chen K,Liu L,Cooper MP,Vita JA,Keaney JF Jr

    更新日期:2013-09-13 00:00:00

  • Cardioselective beta-adrenoceptor blocking actions of some 2-methoxyphenylethanolamines in guinea pig tissues.

    abstract::A series of new phenylethanolamines with 2-methoxy and/or 4-methyl, 4-chloro, or 4-bromo ring substituents and either N-isopropyl or N-tert butyl substituents have been synthesized and tested for beta 1- and beta 2-adrenoceptor blocking activity using isolated guinea pig atrial and tracheal preparations. Each of the d...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:

    authors: Letts LG,Temple DM,Williams LR

    更新日期:1980-06-01 00:00:00

  • Functional coronary microvascular injury evident as increased permeability due to brief ischemia and reperfusion.

    abstract::Although morphological studies suggest that coronary vascular injury is a result of prolonged ischemia and subsequent reperfusion, whether functional coronary microvascular injury develops during brief in vivo ischemia is unclear. In other organs, permeability is a sensitive indicator of functional vascular injury. Th...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.66.4.986

    authors: Dauber IM,VanBenthuysen KM,McMurtry IF,Wheeler GS,Lesnefsky EJ,Horwitz LD,Weil JV

    更新日期:1990-04-01 00:00:00

  • Heart failure gene therapy: the path to clinical practice.

    abstract::Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses fo...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.113.300269

    authors: Pleger ST,Brinks H,Ritterhoff J,Raake P,Koch WJ,Katus HA,Most P

    更新日期:2013-08-30 00:00:00

  • Induction of insulin-like growth factor I messenger RNA in rat aorta after balloon denudation.

    abstract::Insulin-like growth factor I (IGF-I) is a widely distributed mitogen that mediates the growth-promoting effects of platelet-derived growth factor in mesenchymal cells. We show that rat aortic IGF-I messenger RNA (mRNA) is induced 24 hours after deendothelialization, at a time when smooth muscle cell proliferation with...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.66.6.1755

    authors: Cercek B,Fishbein MC,Forrester JS,Helfant RH,Fagin JA

    更新日期:1990-06-01 00:00:00

  • Reflex regulation of sympathetic activity in the spontaneously hypertensive rat.

    abstract::The influence that the pressure-sensitive receptors in the cardiovascular system have on renal nerve activity and on heart rate was compared in normotensive rats (NTR) and spontaneously hypertensive rats (SHR). The cardiovascular receptors were stimulated by raising the blood pressure (BP) with intravenous phenylephri...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.40.6.571

    authors: Coote JH,Sato Y

    更新日期:1977-06-01 00:00:00

  • The influence of combined intra-aortic balloon counterpulsation and hyperosomotic mannitol on regional myocardial blood flow in ischemic myocardium in the dog.

    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

    authors: Watson JT,Fixler DE,Platt MR,Nall BB,Jett GK,Willerson JT

    更新日期:1976-06-01 00:00:00

  • Binding of charged ferritin to alveolar wall components and charge selectivity of macromolecular transport in permeability pulmonary edema in rats.

    abstract::Rat lungs were inflated and incubated in either anionic or cationic ferritin, and alveolar and capillary basement membranes were examined by electron microscopy. Cationic ferritin bound to heparan sulfate proteoglycans on the external surface of the alveolar basement membrane, whereas cationic ferritin bound to the la...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.55.2.155

    authors: Brody JS,Vaccaro CA,Hill NS,Rounds S

    更新日期:1984-08-01 00:00:00

  • Pulmonary hypertension in transgenic mice expressing a dominant-negative BMPRII gene in smooth muscle.

    abstract::Bone morphogenetic peptides (BMPs), a family of cytokines critical to normal development, were recently implicated in the pathogenesis of familial pulmonary arterial hypertension. The type-II receptor (BMPRII) is required for recognition of all BMPs, and targeted deletion of BMPRII in mice results in fetal lethality b...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000126047.82846.20

    authors: West J,Fagan K,Steudel W,Fouty B,Lane K,Harral J,Hoedt-Miller M,Tada Y,Ozimek J,Tuder R,Rodman DM

    更新日期:2004-04-30 00:00:00

  • Evolving Treatments for Arterial and Venous Thrombosis: Role of the Direct Oral Anticoagulants.

    abstract::The direct oral anticoagulants (DOACs) represent a major advance in oral anticoagulant therapy and have replaced the vitamin K antagonists as the preferred treatment for many indications. By simplifying long-term anticoagulant therapy and improving its safety, the DOACs have the potential to reduce the global burden o...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.116.306925

    authors: Chan NC,Eikelboom JW,Weitz JI

    更新日期:2016-04-29 00:00:00

  • Signal transducer and activator of transcription 3 is required for myocardial capillary growth, control of interstitial matrix deposition, and heart protection from ischemic injury.

    abstract::The transcription factor signal transducer and activator of transcription 3 (STAT3) participates in a wide variety of physiological processes and directs seemingly contradictory responses such as proliferation and apoptosis. To elucidate its role in the heart, we generated mice harboring a cardiomyocyte-restricted kno...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000134921.50377.61

    authors: Hilfiker-Kleiner D,Hilfiker A,Fuchs M,Kaminski K,Schaefer A,Schieffer B,Hillmer A,Schmiedl A,Ding Z,Podewski E,Podewski E,Poli V,Schneider MD,Schulz R,Park JK,Wollert KC,Drexler H

    更新日期:2004-07-23 00:00:00

  • Intussusceptive angiogenesis: its role in embryonic vascular network formation.

    abstract::Intussusceptive angiogenesis is a novel mode of blood vessel formation and remodeling, which occurs by internal division of the preexisting capillary plexus without sprouting. In this study, the process is demonstrated in developing chicken eye vasculature and in the chorioallantoic membrane by methylmethacrylate (Mer...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.86.3.286

    authors: Djonov V,Schmid M,Tschanz SA,Burri PH

    更新日期:2000-02-18 00:00:00

  • Resting membrane potential, extracellular potassium activity, and intracellular sodium activity during acute global ischemia in isolated perfused guinea pig hearts.

    abstract::Transmembrane potentials, extracellular potassium activity, and intracellular sodium activity were determined during acute global ischemia in Langendorff perfused guinea pig ventricles by microelectrode techniques. Resting membrane potential decreased with a sigmoidal time course from -82 mV to -49.5 +/- 2.7 mV (SD, n...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.52.4.442

    authors: Kléber AG

    更新日期:1983-04-01 00:00:00

  • Restoration of resting sarcomere length after uniaxial static strain is regulated by protein kinase Cepsilon and focal adhesion kinase.

    abstract::Physiological or pathological stresses and strains produce longer or wider muscle cells, but resting sarcomere length remains constant. Our goal was to investigate the cellular mechanisms for controlling this optimal, resting sarcomere length. To do so, we cultured neonatal rat cardiomyocytes on microfabricated peg-an...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000121101.32286.C8

    authors: Mansour H,de Tombe PP,Samarel AM,Russell B

    更新日期:2004-03-19 00:00:00

  • Protective Effects of Activated Myofibroblasts in the Pressure-Overloaded Myocardium Are Mediated Through Smad-Dependent Activation of a Matrix-Preserving Program.

    abstract:RATIONALE:The heart contains abundant interstitial and perivascular fibroblasts. Traditional views suggest that, under conditions of mechanical stress, cytokines, growth factors, and neurohumoral mediators stimulate fibroblast activation, inducing ECM (extracellular matrix) protein synthesis and promoting fibrosis and ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.118.314438

    authors: Russo I,Cavalera M,Huang S,Su Y,Hanna A,Chen B,Shinde AV,Conway SJ,Graff J,Frangogiannis NG

    更新日期:2019-04-12 00:00:00

  • Changes in extracellular and intracellular pH in ischemic rabbit papillary muscle.

    abstract::The extracellular pH (pHo) and intracellular pH (pHi) were simultaneously measured with H(+)-sensitive microelectrodes in the rabbit papillary muscle during normal arterial perfusion and no-flow ischemia. The preparation was kept in an artificial gaseous atmosphere (N2 and CO2 during ischemia) without a surrounding fl...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.71.2.460

    authors: Yan GX,Kléber AG

    更新日期:1992-08-01 00:00:00

  • Skinned fibers of human atrium and ventricle: myosin isoenzymes and contractility.

    abstract::Different myosin isoenzymes of pig and human atrium and ventricle and rat ventricle were characterized by two approaches: pyrophosphate polyacrylamide gel electrophoresis (PP-PAGE) and analysis of the myosin P light chains by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). We further investigated the rel...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.62.3.632

    authors: Morano I,Arndt H,Gärtner C,Rüegg JC

    更新日期:1988-03-01 00:00:00

  • Analysis of Cardiac Myocyte Maturation Using CASAAV, a Platform for Rapid Dissection of Cardiac Myocyte Gene Function In Vivo.

    abstract:RATIONALE:Loss-of-function studies in cardiac myocytes (CMs) are currently limited by the need for appropriate conditional knockout alleles. The factors that regulate CM maturation are poorly understood. Previous studies on CM maturation have been confounded by heart dysfunction caused by whole organ gene inactivation....

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.116.310283

    authors: Guo Y,VanDusen NJ,Zhang L,Gu W,Sethi I,Guatimosim S,Ma Q,Jardin BD,Ai Y,Zhang D,Chen B,Guo A,Yuan GC,Song LS,Pu WT

    更新日期:2017-06-09 00:00:00

  • Flow-related responses of intracellular inositol phosphate levels in cultured aortic endothelial cells.

    abstract::In vitro and in vivo evidence indicates that hemodynamic wall shear stress evokes a diversity of biological responses in vascular endothelial cells, ranging from cell shape changes to alterations in low density lipoprotein receptor expression. The signal transduction mechanisms by which the level of fluid mechanical s...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.72.4.827

    authors: Prasad AR,Logan SA,Nerem RM,Schwartz CJ,Sprague EA

    更新日期:1993-04-01 00:00:00

  • Effect of in vitro organic nitrate tolerance on relaxation, cyclic GMP accumulation, and guanylate cyclase activation by glyceryl trinitrate and the enantiomers of isoidide dinitrate.

    abstract::Previously, it was shown that the D enantiomer of isoidide dinitrate was 10-fold more potent than the L enantiomer and 10-fold less potent than glyceryl trinitrate for stimulating cyclic GMP accumulation and relaxation of isolated rat aorta. In the present study, these organic nitrates were tested for their ability to...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.63.4.693

    authors: Bennett BM,Schröder H,Hayward LD,Waldman SA,Murad F

    更新日期:1988-10-01 00:00:00

  • Mechanisms that regulate macrophage burden in atherosclerosis.

    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 nee...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.114.301174

    authors: Randolph GJ

    更新日期:2014-05-23 00:00:00

  • Changes in shear stress-related gene expression after experimentally altered venous return in the chicken embryo.

    abstract::Hemodynamics play an important role in cardiovascular development, and changes in blood flow can cause congenital heart malformations. The endothelium and endocardium are subjected to mechanical forces, of which fluid shear stress is correlated to blood flow velocity. The shear stress responsive genes lung Krüppel-lik...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000171901.40952.0d

    authors: Groenendijk BC,Hierck BP,Vrolijk J,Baiker M,Pourquie MJ,Gittenberger-de Groot AC,Poelmann RE

    更新日期:2005-06-24 00:00:00

  • Effect of lidocaine on the early inward transient current in sheep cardiac Purkinje fibers.

    abstract::We used two experimental techniques to study the effect of lidocaine hydrochloride on the early inward transient (sodium) current as it is reflected by the maximum rate of change of action potential phase 0 (Vmax). We assessed the effect of lidocaine on Vmax as Purkinje fibers were slowly depolarized by increasing the...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.37.5.630

    authors: Weld FM,Bigger JT Jr

    更新日期:1975-11-01 00:00:00

  • Cell replication in the arterial wall: activation of signaling pathway following in vivo injury.

    abstract::This study examined intracellular signal events of arterial cells following balloon catheter injury to rat carotid artery. Within 30 minutes, a marked increase in extracellular signal-regulated kinase-1/2 (ERK1/2) activity was observed. This activity remained elevated for 12 hours but had decreased to control levels b...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.82.6.713

    authors: Koyama H,Olson NE,Dastvan FF,Reidy MA

    更新日期:1998-04-06 00:00:00

  • Long-chain acylcarnitines mediate the hypoxia-induced increase in alpha 1-adrenergic receptors on adult canine myocytes.

    abstract::To elucidate the mechanisms responsible for the increase in alpha 1-adrenergic receptors during ischemia in vivo, we developed a procedure for measuring alpha 1-adrenergic receptors in isolated, calcium-tolerant adult canine myocytes. Specific [3H]prazosin binding was rapid, saturable, reversible, and demonstrated the...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.61.5.735

    authors: Heathers GP,Yamada KA,Kanter EM,Corr PB

    更新日期:1987-11-01 00:00:00

  • Angiotensin II and angiotensin III in rat blood.

    abstract::Angiotensin II and its metabolites, [des-Asp-1]-angiotensin II (angiotensin III), [des-(Asp-1,Arg-2)]angiotensin II, and [des-(Asp-1,Arg-2,val-3)]angiotensin II, were measured in arterial and venous plasma from normal rats. Paper chromatography was used to separate the peptides which were measured with a radioimmunoas...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.38.6.122

    authors: Semple PF,Morton JJ

    更新日期:1976-06-01 00:00:00

  • Phosphate regulation of vascular smooth muscle cell calcification.

    abstract::Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralizat...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.87.7.e10

    authors: Jono S,McKee MD,Murry CE,Shioi A,Nishizawa Y,Mori K,Morii H,Giachelli CM

    更新日期:2000-09-29 00:00:00

  • Nuclear factor-kappaB and cAMP response element binding protein mediate opposite transcriptional effects on the Flk-1/KDR gene promoter.

    abstract::-The vascular endothelial growth factor receptor Flk-1/KDR is highly expressed during development and almost disappears in adult tissues. Despite its biological relevance, little is known about the molecular mechanisms controlling its expression. In the present work, it is shown that cAMP response element binding prot...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:

    authors: Illi B,Puri P,Morgante L,Capogrossi MC,Gaetano C

    更新日期:2000-06-23 00:00:00

  • Failure of calcineurin inhibitors to prevent pressure-overload left ventricular hypertrophy in rats.

    abstract::A rapidly emerging body of literature implicates a pivotal role for the Ca2+-calmodulin-dependent phosphatase calcineurin as a cellular target for a variety of Ca2+-dependent signaling pathways culminating in left ventricular hypertrophy (LVH). Most of the recent experimental support for this hypothesis is derived fro...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.84.6.722

    authors: Zhang W,Kowal RC,Rusnak F,Sikkink RA,Olson EN,Victor RG

    更新日期:1999-04-02 00:00:00