Abstract:
AIMS:Antihypertensive drugs are included in the medical therapy of vascular Ehlers-Danlos syndrome (vEDS). The β-blocker celiprolol has been suggested to prevent arterial damage in vEDS, but the underlying mechanism remains unclear. It is also unknown whether the widely used angiotensin II receptor type 1 antagonist losartan has a therapeutic effect in vEDS. Here, we evaluated the impact of celiprolol and losartan on the biomechanical integrity of the vEDS thoracic aorta. METHODS AND RESULTS:We established a new approach to measure the maximum tensile force at rupture of uniaxially stretched murine thoracic aortic rings. In a vEDS model, which we (re-)characterized here at molecular level, heterozygous mice showed a significant reduction in the rupture force compared to wild-type mice, reflecting the increased mortality due to aortic rupture. For the assessment of treatment effects, heterozygous mice at 4 weeks of age underwent a 4-week treatment with celiprolol, losartan, and, as a proof-of-concept drug, the matrix metalloproteinase inhibitor doxycycline. Compared to age- and sex-matched untreated heterozygous mice, treatment with doxycycline or celiprolol resulted in a significant increase of rupture force, whereas no significant change was detected upon losartan treatment. CONCLUSIONS:In a vEDS model, celiprolol or doxycycline, but not losartan, can improve the biomechanical integrity of the aortic wall, thereby potentially reducing the risk of dissection and rupture. As doxycycline is a broad-spectrum antibiotic with considerable side effects, celiprolol may be more suitable for a long-term therapy and thus rather indicated for the medication of patients with vEDS.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Dubacher N,Münger J,Gorosabel MC,Crabb J,Ksiazek AA,Caspar SM,Bakker ENTP,van Bavel E,Ziegler U,Carrel T,Steinmann B,Zeisberger S,Meienberg J,Matyas Gdoi
10.1093/cvr/cvz095subject
Has Abstractpub_date
2020-02-01 00:00:00pages
457-465issue
2eissn
0008-6363issn
1755-3245pii
5432647journal_volume
116pub_type
杂志文章abstract::Known viable allograft canine pulmonary valves were inserted in an isotopic position ensuring normal physiological function and simulating the clinical situation. Valves removed at periods up to eight weeks were assessed for viability using previously established criteria of tissue culture and protein and collagen syn...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.1.78
更新日期:1977-01-01 00:00:00
abstract:OBJECTIVE:We recently demonstrated in our swine model of coronary artery spasm that enhanced myosin light chain (MLC) phosphorylations (both MLC mono- and diphosphorylations) play a central role in the pathogenesis of the spasm. However, the molecular mechanism for and the phosphorylation sites for the enhanced MLC pho...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00144-3
更新日期:1999-09-01 00:00:00
abstract:AIMS:Sulfur dioxide (SO₂) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that cont...
journal_title:Cardiovascular research
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doi:10.1093/cvr/cvt057
更新日期:2013-07-01 00:00:00
abstract::Mechanical stress signals transmitted through the heart walls during hemodynamic loading are sensed by the myocytes, which respond with changes in contractile performance and gene expression. External forces play an important role in physiological heart development and hypertrophy, but disruption of the well-balanced ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2007.03.029
更新日期:2008-03-01 00:00:00
abstract:OBJECTIVE:The mechanosensitive nonselective cation channel (NSC(MS)) and endothelin-1 (ET-1) play critical roles in the regulation of vascular tone. This study was undertaken to investigate the effect of ET-1 on NSC(MS) and on the myogenic response of arteries. METHODS:Cell-attached patch-clamp techniques were applied...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.06.021
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVE:Myogenic tone, which has a major role in the regulation of local blood flow, refers to the ability of vascular smooth muscle to adapt its contractility to changes in transmural pressure. Although Rho-kinase is involved in myogenic tone, the pathway involved remains unclear, especially concerning translocation...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.10.020
更新日期:2007-01-01 00:00:00
abstract::Inflammation represents the driving feature of many diseases, including atherosclerosis, cancer, autoimmunity and infections. It is now established that metabolic processes shape a proper immune response and within this context the alteration in cellular cholesterol homeostasis has emerged as a culprit of many metabol...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvz127
更新日期:2019-07-01 00:00:00
abstract:AIMS:To compare ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) mortality between Sweden and the UK, adjusting for background population rates of expected death, case mix, and treatments. METHODS AND RESULTS:National data were collected from hospitals in Sweden [n = 73 hospitals, 180 368 pati...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvz197
更新日期:2020-01-01 00:00:00
abstract:AIMS:This study aimed at characterizing expression and the functional role of the Gjb6 gene, encoding for connexin 30 (Cx30) protein, in the adult mouse heart. METHODS AND RESULTS:The expression of the Gjb6 gene in the mouse heart was investigated by RT-PCR and sequencing of amplified cDNA fragments. The sites of Gjb6...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp280
更新日期:2010-01-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:
更新日期:1996-10-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00403-4
更新日期:2000-03-01 00:00:00
abstract:OBJECTIVE:In isolated cardiac preparations of non-failing hearts from different species, including man, there is a positive force-frequency relation which is reversed into a negative relation in preparation from failing hearts. Whether or not such relations between ventricular function and heart rate hold true in the i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00246-0
更新日期:1998-02-01 00:00:00
abstract::Arteriogenesis, the process of collateral artery growth as an adaptation to major arterial occlusion, can be life- and tissue saving and may alter the natural course of the consequences and organ manifestations of arterial disease. This is achieved by an active growth process that is coupled to complete arterial remod...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(99)00191-1
更新日期:1999-09-01 00:00:00
abstract:OBJECTIVE:Macrophage migration inhibitory factor (MIF), which plays a pivotal role in the control of inflammatory responses, was first characterized as a T-cell cytokine, but later was also found as a pituitary peptide released in response to infection and stress. However, MIF's role and expression in the myocardium ha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00408-4
更新日期:2001-12-01 00:00:00
abstract:OBJECTIVE:The aim was to test the hypothesis that A1 receptor mediated cardioprotection by endogenous adenosine is exerted during ischaemia rather than reperfusion. METHODS:Anaesthetised open chest rabbits were subjected to 30 min regional ischaemia and 120 min reperfusion, and randomised to one of six groups: group I...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.2.270
更新日期:1994-02-01 00:00:00
abstract::Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the 1970s. Exponential growth of free radical research occurred after the discovery...
journal_title:Cardiovascular research
pub_type: 社论,评审
doi:10.1016/s0008-6363(98)00244-2
更新日期:1998-12-01 00:00:00
abstract::Nitric oxide (NO) is a highly reactive, free radical signalling molecule that is constitutively released in cardiomyocytes by both the endothelial and neuronal isoforms of nitric oxide synthase (eNOS and nNOS, respectively). There are increasing data indicating that NO modulates various proteins involved in excitation...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvm012
更新日期:2008-01-15 00:00:00
abstract::The role of mediators of inflammation in the pathogenesis and evolution of myocardial infarction has attracted increased interest as interventions which inhibit the inflammatory response after coronary artery occlusion have been shown to decrease infarct size. The distribution of fibrinogen and albumin in ischaemia my...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.1.36
更新日期:1986-01-01 00:00:00
abstract:AIMS:In mammalian ventricles, electrical gradients establish electrical heterogeneities as essential tissue mechanisms to optimize mechanical efficiency and safeguard electrical stability. Electrical gradients shape mammalian electrocardiographic patterns; disturbance of electrical gradients is proarrhythmic. The zebra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa238
更新日期:2020-07-31 00:00:00
abstract:AIMS:Atrial fibrillation (AF) is the most common cardiac arrhythmia, and early-onset lone AF has been linked to mutations in genes encoding ion channels. Mutations in the pore forming subunit KV4.3 leading to an increase in the transient outward potassium current (Ito) have previously been associated with the Brugada S...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt028
更新日期:2013-06-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to evaluate the protective effect of verapamil during myocardial ischaemia and reperfusion. DESIGN:In vivo phosphorus-31 (31P) magnetic resonance spectroscopy was performed on rats pretreated with verapamil (mg.kg-1 intraperitoneal) and controls during a 45 min left coronary artery occlusio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.2.101
更新日期:1991-02-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy181
更新日期:2019-02-01 00:00:00
abstract::In this study we report about the modulation of connexin45 (Cx45) gap junction channel properties by phosphorylation of the connexin molecules through different protein kinases. Phosphorylation of Cx45 was studied in HeLa cells transfected with mouse Cx45 (mCx45). Using Western blotting (WB) and immunocytochemistry, t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00047-x
更新日期:2000-06-01 00:00:00
abstract:OBJECTIVE:The presence is well established in unstable angina of intracoronary thrombosis in a stenosed epicardial coronary artery. The effects of the thrombus formation on the distal microcirculation are however still unclear. METHODS:We adapted the Folts canine model of left circumflex coronary arterial stenosis and...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00270-3
更新日期:1999-04-01 00:00:00
abstract:OBJECTIVE:Stretch-activated cation channels (SAC) have been suggested to act as endothelial mechanosensors for hemodynamic forces. Ca(2+) influx through SAC could induce an intracellular Ca(2+) signal stimulating Ca(2+)-dependent synthesis of vasodilators like NO, prostacyclin, or EDHF. In the present study we tested w...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00476-x
更新日期:2002-01-01 00:00:00
abstract::The left ansa subclavia was stimulated at supramaximal intensity at a frequency of Hz in open-chest, anaesthetized dogs for periods of about 10 min. Arterial blood pressure, myocardial contractile force, and coronary sinus blood flow reached peak values after 1 or 2 min of stimulation, and then declined gradually thro...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.5.549
更新日期:1976-09-01 00:00:00
abstract::Integrative genomics studies have greatly advanced our understanding of cardiovascular pathophysiology over the last decade. Here, we highlight the strengths and challenges of this cutting-edge approach and provide examples where novel insights have arisen through the integration of multi-level genomic information and...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvs303
更新日期:2013-03-15 00:00:00
abstract:OBJECTIVE:Migration and proliferation of arterial smooth muscle cells are critical responses during restenosis after balloon angioplasty. We investigated the changes in the expression of Ca(2+) channels and dystrophin, two determinants of contraction, after balloon injury of rat aortas. METHODS:Proliferation and migra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00210-8
更新日期:2001-01-01 00:00:00
abstract:OBJECTIVE:The aim was to evaluate in a minipig model of acute myocardial infarction the cardioprotection provided by the beta adrenoceptor blocking and vasodilating activities present in carvedilol; comparison was made to the pure beta adrenoceptor antagonist, propranolol. METHODS:Experiments were performed in 25 Yuca...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.5.518
更新日期:1992-05-01 00:00:00
abstract:AIMS:Both mitochondria and nitric oxide (NO*) contribute to cardioprotection by ischaemic preconditioning (IPC). IPC causes mild uncoupling of mitochondria via uncoupling proteins (UCPs) and the adenine nucleotide translocase (ANT), and mild uncoupling per se is cardioprotective. Although electrophilic lipids are known...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn323
更新日期:2009-05-01 00:00:00