Integrin-mediated transcriptional activation of inhibitor of apoptosis proteins protects smooth muscle cells against apoptosis induced by degraded collagen.


:Apoptosis of smooth muscle cells (SMC) and degradation of the extracellular matrix (ECM) have both been implicated in atherosclerotic plaque rupture. We have previously reported that degraded type I collagen fragments induce a rapid but transient apoptotic burst initiated by calpains in SMC. The aim of the current study was to identify the pathway responsible for consecutive SMC survival. We show that exposure of SMC to collagen fragments resulted in a sustained activation of nuclear factor (NF)-kappaB via phosphorylation and degradation of IkappaBalpha. Its prevention through retroviral expression of superrepressor IkappaBalpha or proteasome inhibition potently induced apoptosis. In the presence of blocking antibodies to alpha(v)beta(3) integrin and RGD peptides, collagen fragments no longer activated NF-kappaB and apoptosis was enhanced. The mechanism by which NF-kappaB was protecting SMC against collagen fragment-induced apoptosis was a transcriptional activation of several endogenous caspase inhibitors of the inhibitor of apoptosis protein (IAP) family as: (1) the expression of xIAP, c-IAP2, and survivin was potently induced by collagen fragments; (2) IAP expression was abrogated by superrepressor IkappaBalpha; and (3) knockdown of each of the 3 IAPs by small interfering RNA (siRNA) resulted in enhanced apoptosis after collagen fragment treatment. Our data suggest that SMC exposed to degraded collagen are protected against apoptosis by a mechanism involving alpha(v)beta(3)-dependent NF-kappaB activation with consequent activation of IAPs. This may constitute a novel antiapoptotic pathway ensuring SMC survival in settings of enhanced ECM degradation such as cell migration, vascular remodeling, and atherosclerotic plaque rupture.


Circ Res


Circulation research


von Wnuck Lipinski K,Keul P,Ferri N,Lucke S,Heusch G,Fischer JW,Levkau B




Has Abstract


2006-06-23 00:00:00














  • Role of small GTPases in endothelial cytoskeletal dynamics and the shear stress response.

    abstract::Fluid shear stress caused by blood flow is a major determinant of vascular remodeling and arterial tone and can lead to development of atherosclerosis. The endothelial monolayer in vivo acts as a signal transduction interface for hemodynamic forces; these forces determine the shape, cytoskeletal organization, and func...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Tzima E

    更新日期:2006-02-03 00:00:00

  • G-CSF for Extensive STEMI.

    abstract:RATIONALE:In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment-elevation myocardial infarction and left ventricular (LV) dysfunction after successf...

    journal_title:Circulation research

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Achilli F,Pontone G,Bassetti B,Squadroni L,Campodonico J,Corrada E,Facchini C,Mircoli L,Esposito G,Scarpa D,Pidello S,Righetti S,Di Gennaro F,Guglielmo M,Muscogiuri G,Baggiano A,Limido A,Lenatti L,Di Tano G,Malafron

    更新日期:2019-07-19 00:00:00

  • The effect of hypoxia on the regional distribution of cardiac output in the dog.

    abstract::Twenty-one dogs were studied under conditions of normal oxygenation and hypoxia with the microsphere distribution method to determine the effect of arterial oxygen saturation on the regional distribution of cardiac output. The dogs were anesthetized and artifically ventilated. Cannulas were placed in the left ventricl...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Adachi H,Strauss W,Ochi H,Wagner HN Jr

    更新日期:1976-09-01 00:00:00

  • Experimental, Systems, and Computational Approaches to Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor Cell-Derived Exosomes From Pediatric Patients.

    abstract:RATIONALE:Studies have demonstrated that exosomes can repair cardiac tissue post-myocardial infarction and recapitulate the benefits of cellular therapy. OBJECTIVE:We evaluated the role of donor age and hypoxia of human pediatric cardiac progenitor cell (CPC)-derived exosomes in a rat model of ischemia-reperfusion inj...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Agarwal U,George A,Bhutani S,Ghosh-Choudhary S,Maxwell JT,Brown ME,Mehta Y,Platt MO,Liang Y,Sahoo S,Davis ME

    更新日期:2017-02-17 00:00:00

  • Altered Na+ channels promote pause-induced spontaneous diastolic activity in long QT syndrome type 3 myocytes.

    abstract::Long QT syndrome (LQTS) type 3 (LQT3), typified by the DeltaKPQ mutation (LQT3 mutation in which amino acid residues 1505 to 1507 [KPQ] are deleted), is caused by increased sodium entry during the action potential plateau resulting from mutation-altered inactivation of the Na(v)1.5 channel. Although rare, LQT3 is the ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Fredj S,Lindegger N,Sampson KJ,Carmeliet P,Kass RS

    更新日期:2006-11-24 00:00:00

  • Collagen-stimulated human platelet aggregation is mediated by endogenous calcium-activated neutral protease.

    abstract::To clarify the physiological role of calcium-activated neutral protease (CANP) in human platelets, we loaded the platelets with a Ca2+ -sensitive fluorescent dye, fura-2, and measured the degree of aggregation, cytosolic calcium ion concentration [( Ca2+]i), and proteolysis by sodium dodecyl sulfate-polyacrylamide gel...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Toyo-oka T,Shin WS,Okai Y,Dan Y,Morita M,Iizuka M,Sugimoto T

    更新日期:1989-02-01 00:00:00

  • Balloon-induced right ventricular outflow obstruction: a new approach to control of acute interventricular shunting after myocardial infarction in canines and swine.

    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


    authors: Babb JD,Waldhausen JA,Zelis R

    更新日期:1977-04-01 00:00:00

  • minK-related peptide 1 associates with Kv4.2 and modulates its gating function: potential role as beta subunit of cardiac transient outward channel?

    abstract::Inherited mutations and a polymorphism in minK-related peptide 1 (MiRP1) have been linked to congenital or acquired long-QT syndrome, pointing to the importance of MiRP1 in maintaining the cardiac electrical stability. We tested whether MiRP1 could affect the function of Kv4.x (x=2 and 3), the major pore-forming (alph...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Zhang M,Jiang M,Tseng GN

    更新日期:2001-05-25 00:00:00

  • Hypoxia and hypoxia/reoxygenation activate Raf-1, mitogen-activated protein kinase kinase, mitogen-activated protein kinases, and S6 kinase in cultured rat cardiac myocytes.

    abstract::In response to hypoxia and reoxygenation, mammalian cells are known to express a variety of genes to adapt to these external stresses or lead to further cell damage. We investigated the intracellular signaling cascades in cultured rat cardiac myocytes subjected to hypoxia followed by reoxygenation (hypoxia/reoxygenati...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Seko Y,Tobe K,Ueki K,Kadowaki T,Yazaki Y

    更新日期:1996-01-01 00:00:00

  • Regulation of calcium current by intracellular calcium in smooth muscle cells of rabbit portal vein.

    abstract::Effects of concentrations of intracellular calcium, [Ca2+]i, on the voltage-dependent Ca2+ current (ICa) recorded from dispersed single smooth muscle cells of the rabbit portal vein were studied, using a whole cell voltage clamp method combined with an intracellular perfusion technique. Outward currents were minimized...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Ohya Y,Kitamura K,Kuriyama H

    更新日期:1988-02-01 00:00:00

  • DIDS-sensitive pHi regulation in single rat cardiac myocytes in nominally HCO3-free conditions.

    abstract::The fluorescent dye 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) was used to measure pHi in the spontaneously hypertensive rat (SHR) and in normal rat cardiac myocytes under nominally HCO3-free (20 mmol/L HEPES-buffered) conditions. When only the Na-H exchanger was blocked, the intrinsic buffering power (bet...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Wu ML,Tsai ML,Tseng YZ

    更新日期:1994-07-01 00:00:00

  • Morphometry of exercise-induced right ventricular hypertrophy in the rat.

    abstract::In our morphometric study of the effects of exercise on the heart, male Wistar-Kyoto rats at 5 weeks of age were subjected daily to a moderate treadmill running program that lasted for 7 weeks. The heart responded to physical conditioning by different magnitudes of tissue growth of the right (22%) and left (7%) ventri...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Anversa P,Levicky V,Beghi C,McDonald SL,Kikkawa Y

    更新日期:1983-01-01 00:00:00

  • Length-induced changes in activation during contraction. A study of mechanical oscillations in strontium-mediated contractions of cat and frog heart muscle.

    abstract::The plateau phase of prolonged Sr-mediated contractions of preparations of cat and frog heart muscle was used to study the transient response to abrupt changes in load or length. An oscillatory response (total amplitude equal to or less than 5% Lmax) was obtained. Isotonic oscillations were less damped than their isom...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Henderson AH,Cattell MR

    更新日期:1976-04-01 00:00:00

  • Pulmonary vascular impedance analysis of adaptation to chronically elevated blood flow in the awake dog.

    abstract::Pulsatile pulmonary hemodynamics were analyzed in a chronic awake canine high flow model. Standard mean flow and pulsatile flow hemodynamics were measured and alterations in the proximal pulmonary vascular physical properties were quantified by the characteristic impedance (Zo). Pulmonary vascular resistance (PVR), wh...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Hopkins RA,Hammon JW Jr,McHale PA,Smith PK,Anderson RW

    更新日期:1979-08-01 00:00:00

  • Ankyrin-G coordinates intercalated disc signaling platform to regulate cardiac excitability in vivo.

    abstract:RATIONALE:Nav1.5 (SCN5A) is the primary cardiac voltage-gated Nav channel. Nav1.5 is critical for cardiac excitability and conduction, and human SCN5A mutations cause sinus node dysfunction, atrial fibrillation, conductional abnormalities, and ventricular arrhythmias. Further, defects in Nav1.5 regulation are linked wi...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Makara MA,Curran J,Little SC,Musa H,Polina I,Smith SA,Wright PJ,Unudurthi SD,Snyder J,Bennett V,Hund TJ,Mohler PJ

    更新日期:2014-11-07 00:00:00

  • Knockout mice for pharmacological screening: testing the specificity of Na+-Ca2+ exchange inhibitors.

    abstract::The role of the Na+-Ca2+ exchanger as a major determinant of cell Ca2+ is well defined in cardiac tissue, and there has been much effort to develop specific inhibitors of the exchanger. We use a novel system to test the specificity of two putative specific inhibitors, KB-R7943 and SEA0400. The drugs are applied to ele...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Reuter H,Henderson SA,Han T,Matsuda T,Baba A,Ross RS,Goldhaber JI,Philipson KD

    更新日期:2002-07-26 00:00:00

  • Contribution of Na(+)-Ca2+ exchange to stimulation of transient inward current by isoproterenol in rabbit cardiac Purkinje fibers.

    abstract::Cellular mechanisms underlying beta-adrenergic stimulation of the arrhythmogenic transient inward current (TI) were investigated by using a two-microelectrode voltage-clamp technique in rabbit cardiac Purkinje fibers. TI induced by elevating [Ca2+]o to 30 mmol/L and substituting [Na+]o with N-methyl-D-glucamine (NMG) ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Han X,Ferrier GR

    更新日期:1995-04-01 00:00:00

  • Contribution of endothelial cells to calcium-dependent fluorescence transients in rabbit hearts loaded with indo 1.

    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


    authors: Lorell BH,Apstein CS,Cunningham MJ,Schoen FJ,Weinberg EO,Peeters GA,Barry WH

    更新日期:1990-08-01 00:00:00

  • Endothelial NO-Synthase Gene-Enhanced Progenitor Cell Therapy for Pulmonary Arterial Hypertension: The PHACeT Trial.

    abstract:RATIONALE:Pulmonary arterial hypertension (PAH) remains a progressive and eventually lethal disease characterized by increased pulmonary vascular resistance because of loss of functional lung microvasculature, primarily at the distal (intracinar) arteriolar level. Cell-based therapies offer the potential to repair and ...

    journal_title:Circulation research

    pub_type: 杂志文章,多中心研究


    authors: Granton J,Langleben D,Kutryk MB,Camack N,Galipeau J,Courtman DW,Stewart DJ

    更新日期:2015-09-11 00:00:00

  • Sensitization of isolated canine coronary arteries to calcium ions after exposure to cholesterol.

    abstract::The abundance of membrane cholesterol is an important determinant of the functional properties of biomembranes. To determine whether arterial smooth muscle acquires altered contractile properties in a high cholesterol environment, isolated canine coronary arteries were exposed to cholesterol in stable aqueous solution...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Yokoyama M,Henry PD

    更新日期:1979-10-01 00:00:00

  • Coarctation of the aorta and baroreceptor resetting. A study of carotid baroreceptor stimulus-response characteristics before and after surgical repair in the dog.

    abstract::We studied baroreceptor function in dogs before and after surgical repair of coarctation of the aorta by direct recording of multifiber carotid sinus (CS) nerve activity (NA) during alteration of pulsatile arterial pressure with systemic phenylephrine and nitroprusside, and during static pressure changes using a CS po...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Igler FO,Boerboom LE,Werner PH,Donegan JH,Zuperku EJ,Bonchek LI,Kampine JP

    更新日期:1981-03-01 00:00:00

  • Chronic one-kidney hypertension in rabbits. III. Renopressin, a new hypertensive substance.

    abstract::The blood pressure of rabbits with chronic one-kidney hypertension can be lowered to normal by immunization with hog kidney cortex preparations that do not contain renin, thus providing evidence for a new factor essential for the maintenance of an elevated blood pressure. A search for the new factor has led to the dis...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Skeggs LT,Kahn JR,Levine M,Dorer FE,Lentz KE

    更新日期:1977-02-01 00:00:00

  • Regulation of glomerular filtration and proximal tubule reabsorption.

    abstract::In this review current hypotheses for the regulation of filtration rate and the subsequent reabsorption of that filtrate by the proximal tubule are discussed. In the rat the filtration rate is highly plasma flow dependent because of the phenomenon of filtration equilibrium. On the other hand, in man and dog filtration...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Knox FG,Cuche J-L,Ott CE,Diaz-Buxo JA,Marchand G

    更新日期:1975-06-01 00:00:00

  • Molecular mechanisms of mitochondrial autophagy/mitophagy in the heart.

    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


    authors: Saito T,Sadoshima J

    更新日期:2015-04-10 00:00:00

  • Creatine phosphate consumption and the actomyosin crossbridge cycle in cardiac muscles.

    abstract::To investigate the regulation of the actomyosin crossbridge cycle in cardiac muscles, the effects of ATP, ADP, Pi, and creatine phosphate (CP) on the rate of force redevelopment (ktr) were measured. We report that CP is a primary determinant in controlling the actomyosin crossbridge cycling kinetics of cardiac muscles...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Ogut O,Brozovich FV

    更新日期:2003-07-11 00:00:00

  • Ca(V)3.2 channels and the induction of negative feedback in cerebral arteries.

    abstract:RATIONALE:T-type (CaV3.1/CaV3.2) Ca(2+) channels are expressed in rat cerebral arterial smooth muscle. Although present, their functional significance remains uncertain with findings pointing to a variety of roles. OBJECTIVE:This study tested whether CaV3.2 channels mediate a negative feedback response by triggering C...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Harraz OF,Abd El-Rahman RR,Bigdely-Shamloo K,Wilson SM,Brett SE,Romero M,Gonzales AL,Earley S,Vigmond EJ,Nygren A,Menon BK,Mufti RE,Watson T,Starreveld Y,Furstenhaupt T,Muellerleile PR,Kurjiaka DT,Kyle BD,Braun AP,W

    更新日期:2014-09-12 00:00:00

  • Acetylcholine-sensitive intracellular Ca2+ store in fresh endothelial cells and evidence for ryanodine receptors.

    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


    authors: Wang X,Lau F,Li L,Yoshikawa A,van Breemen C

    更新日期:1995-07-01 00:00:00

  • Erythrocyte Metabolic Reprogramming by Sphingosine 1-Phosphate in Chronic Kidney Disease and Therapies.

    abstract:RATIONALE:Hypoxia promotes renal damage and progression of chronic kidney disease (CKD). The erythrocyte is the only cell type for oxygen (O2) delivery. Sphingosine 1-phosphate (S1P)-a highly enriched biolipid in erythrocytes-is recently reported to be induced under high altitude in normal humans to enhance O2 delivery...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Xie T,Chen C,Peng Z,Brown BC,Reisz JA,Xu P,Zhou Z,Song A,Zhang Y,Bogdanov MV,Kellems RE,D'Alessandro A,Zhang W,Xia Y

    更新日期:2020-07-17 00:00:00

  • Changes in intracellular calcium during mechanical alternans in isolated ferret ventricular muscle.

    abstract::Alternans in heart is important as pulsus alternans in cardiac failure and electrophysiological alternans in myocardial ischemia. The explanation of this phenomenon is still unclear. We attempted to investigate the cellular mechanisms of alternans by measuring intracellular free calcium concentration [( Ca2+]i) with t...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Lab MJ,Lee JA

    更新日期:1990-03-01 00:00:00

  • Duration of ischemia is vital for collateral development: repeated brief coronary artery occlusions in conscious dogs.

    abstract::The effects of two types of repeated transient coronary artery occlusions on collateral development were examined in chronically instrumented, conscious dogs. A 2-minute coronary occlusion at 32-minute intervals (group 1, n = 11) or a 15-second occlusion at 4-minute intervals (group 2, n = 7) were repeated day and nig...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Mohri M,Tomoike H,Noma M,Inoue T,Hisano K,Nakamura M

    更新日期:1989-02-01 00:00:00