Abstract:
BACKGROUND:Myeloid differentiation factor 88 (MyD88) is an endogenous adaptor protein that coordinates the inflammatory response to agonists of the Toll-like receptor and interleukin-1 receptor families. This particular response is activated following myocardial ischemia and infarction and may represent a viable target for pharmacologic inhibition. The current study tested MyD88 inhibitors in a murine model of nonreperfused acute myocardial infarction (AMI). METHODS:AMI was induced by permanent ligation of the left coronary artery. Adult, male, Imprinting Control Region mice were randomized to daily injections with 1 of 2 MyD88 pharmacologic inhibitors (ST2825 25 mg/kg or IMG2005 1 mg/kg), saline, or pretreatment with MyD88-targeted silencing small interfering RNA (siRNA) or scrambled nontargeted siRNA (n = 6 for each group). Echocardiography was performed at baseline and 7 days after surgery to evaluate pathologic cardiac enlargement. RESULTS:Pharmacologic inhibition of MyD88 with ST2825 or IMG2005) and MyD88-targeted siRNA protected against left ventricular (LV) dilatation (reduced LV end-systolic and LV end-diastolic diameter) and hypertrophy. This protection occurred despite no measurable reduction in infarct size. CONCLUSIONS:Pharmacologic MyD88 inhibition protects against pathologic LV remodeling without altering infarct scar formation. MyD88 may be a viable target for pharmacologic inhibition in AMI.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Van Tassell BW,Seropian IM,Toldo S,Salloum FN,Smithson L,Varma A,Hoke NN,Gelwix C,Chau V,Abbate Adoi
10.1097/FJC.0b013e3181d3da24subject
Has Abstractpub_date
2010-04-01 00:00:00pages
385-90issue
4eissn
0160-2446issn
1533-4023journal_volume
55pub_type
杂志文章abstract::We investigated the effects of a newly synthesized dihydropyridine (DHP) derivative (NZ-105) on intracellular Ca transients and contraction in ferret ventricular muscles, using the aequorin method. Low concentrations of NZ-105 (10(-9)-10(-7) M) showed no significant effects on the light signal of aequorin and tension ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::We wished to determine whether pharmacologic inhibition of the exaggerated sympathetic nerve activity in congestive heart failure (CHF) could restore the renal response to exogenous atrial natriuretic peptide (ANP) administration. Left ventricular (LV) myocardial infarction was induced in Sprague-Dawley rats (n = 16) ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199011000-00013
更新日期:1990-11-01 00:00:00
abstract::The purpose of this study was to determine whether there are differences in the restoration of endothelial function by angiotensin-converting enzyme inhibition based on the severity of hypertension. Forearm blood flow (FBF) was measured in 69 patients with essential hypertension (mild, n = 23; moderate, n = 29; and se...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-200205000-00007
更新日期:2002-05-01 00:00:00
abstract::The effect of the new vasodilatory and antianginal compound, bepridil (CERM-1978), was examined on the electrical activity of the vascular smooth muscle of isolated dog coronary arteries. Tetraethylammonium (10 mM) was used to induce excitability in the muscle in the form of Ca2+-dependent overshooting action potentia...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198107000-00024
更新日期:1981-07-01 00:00:00
abstract::We investigated the effects of the ATP-dependent K+ channel antagonist glyburide and the ATP-dependent K+ channel agonist pinacidil in a Langendorff-perfused rabbit isolated heart subjected to a period of global hypoxia. A class III antiarrhythmic drug, E-4031, also was studied in this model. These studies aimed to de...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199302000-00001
更新日期:1993-02-01 00:00:00
abstract::Tetrahydrobiopterin is the reduced unconjugated pterin that serves as an essential cofactor for the normal enzymatic function of the aromatic amino acid hydroxylases and for the nitric oxide synthases (NOS). Its role in the latter biochemistry is being increasing appreciated, as depletion or oxidation of BH4 results i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e318123f854
更新日期:2007-09-01 00:00:00
abstract::Nitric oxide (NO) is a potent inhibitor of platelet aggregation. However, the benefits of NO-based therapies can be confounded by concomitant hypotension. Monophosphoryl lipid A (MLA) is a nontoxic derivative of endotoxin that purportedly increases nitric oxide synthase (NOS) activity and, presumably, NO production, y...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200003000-00004
更新日期:2000-03-01 00:00:00
abstract::The possible relevance of intrinsic sympathomimetic activity (ISA) for beta-blocker-induced changes in plasma lipids was investigated by reviewing the literature and analyzing the results separately for nonselective beta-blockers, beta 1-selective beta-blockers, and those possessing ISA. It was confirmed that with the...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198300051-00008
更新日期:1983-01-01 00:00:00
abstract::There is no systematic study in which the effects of vasoactive substances were investigated on pulmonary vascular resistance (PVR) in in vivo mouse by directly measuring cardiac output and the inflow and outflow pressures in the pulmonary circulation. We determined the responses of PVR, total peripheral resistance (T...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000199
更新日期:2015-04-01 00:00:00
abstract::The equilibrating process of catecholamines (CAs) between plasma and red blood cells (RBC) was studied by measuring their erythrocyte/plasma concentration gradient (E/P ratio); ratio of E/P > 1 for a given amine was considered the consequence of its accumulation in or on RBC. We studied in vitro human blood obtained f...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199404000-00002
更新日期:1994-04-01 00:00:00
abstract::Bethanidine sulfate is a congener of bretylium tosylate, which has been reported to have antiarrhythmic and antifibrillatory effects. We studied the effects of bethanidine on transmembrane potentials recorded from canine Purkinje fibers and ventricular muscle cells, using standard microelectrode techniques. Normal Pur...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198501000-00009
更新日期:1985-01-01 00:00:00
abstract::The pharmacologic profile of a novel angiotensin I (AT1) receptor antagonist 606A was studied in various in vitro and in vivo preparations. The 606A showed a high affinity at AT1 receptors [inhibition constant (Ki), 12.8 +/- 0.4 nM] in rabbit adrenal cortical membrane and a low affinity to AT2 receptors (Ki, > 1 mM) i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199702000-00019
更新日期:1997-02-01 00:00:00
abstract::Vascular smooth muscle cell (VSMC) proliferation is pivotal in the progression of hypertension, atherosclerosis, and restenosis. Resveratrol is a grape polyphenol that is implicated as an important contributor to red wine's vascular protective effects. Its antimitogenic action on VSMC is attributed to an array of plei...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318059ae80
更新日期:2007-07-01 00:00:00
abstract::The majority of deaths attributable to hypertension are coronary artery disease (CAD) deaths and, consequently, the prevention of CAD should be the primary aim of hypertension management. Recent meta-analyses confirm the results of the individual hypertension intervention trials, which demonstrated a disappointing sho...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1991-01-01 00:00:00
abstract::The effects of a newly synthesized antiarrhythmic agent, TYB-3823 on the transmembrane action potential were examined in isolated papillary muscles of guinea pig. TYB-3823 (3 x 10(-6)-3 x 10(-5)M) caused a dose-dependent decrease in the maximum upstroke velocity (Vmax) and a shortening of action potential duration (AP...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::In 22 patients with stable myocardial ischemia, we prospectively studied the short- and long-term effects of isosorbide-5-mononitrate (5-ISMN) on dipyridamole-induced myocardial ischemia, the ability of dipyridamole-stress echocardiography to evaluate nitrate tolerance, and the role of activation of the neurohumoral s...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-200007000-00007
更新日期:2000-07-01 00:00:00
abstract::Interspersed between cardiac myocytes, cardiac fibroblasts serve mainly as a structural support during ventricular wall thickening from embryogenesis until adulthood. Cardiac fibroblasts, however, may also serve as a source of mitogens, extracellular matrix proteins, cytokines, and growth factors that could affect the...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e31821209ee
更新日期:2011-05-01 00:00:00
abstract::Coronary arteries from animals on normal diets (ND) exhibit well-maintained responses to dilators under ischemic conditions. The reported altered metabolic requirements and K+-currents in blood vessels from hypercholesterolemic animals fed high-fat diets (HF) led us to hypothesize that under metabolically depressed co...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200404000-00004
更新日期:2004-04-01 00:00:00
abstract::Several studies suggested that dopamine may be one of the inhibitory modulators of aldosterone secretion. Metoclopramide, a selective antagonist for dopamine D-2 receptors, increases both basal plasma aldosterone levels and the aldosterone response to angiotensin II (Ang II) in rats and humans kept on a high sodium in...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1989-01-01 00:00:00
abstract::The objective of this study was to investigate the cardioactive properties of oxybutynin, a drug that is widely prescribed for management of voiding dysfunction. Membrane currents were recorded from whole-cell-configured guinea pig ventricular myocytes, and action potentials were recorded from guinea pig and rabbit pa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200002000-00024
更新日期:2000-02-01 00:00:00
abstract::Although case reports of a possible association between statin therapy and tendon rupture have been published, no analytical studies exploring this relationship have been reported. We conducted a case-control study using the electronic medical records at Michigan State University from 2002 to 2007 to assess whether st...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181a0ce8b
更新日期:2009-05-01 00:00:00
abstract::The pharmacokinetics of losartan and EXP3174, an active metabolite of losartan, were evaluated in the anesthetized pig after both a single intravenous dose (3 mg/kg) and during constant intravenous infusion. The pharmacodynamic activities of losartan and EXP3174 were determined during constant intravenous infusion as ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199711000-00008
更新日期:1997-11-01 00:00:00
abstract::The effects of noradrenaline (NA, 10(-5) M) and [arginine8]vasopressin (AVP, 10(-7) M) on tension in Ca2+-free medium and on membrane potential, and the inhibition of NA- and AVP-induced contractions by isradipine, have been compared in mesenteric resistance vessels (MRVs) from Wistar-Kyoto (WKY) rats. The release of ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::Vasopressin secretion is stimulated by hyperosmolality, hypovolemia, or hypotension and is inhibited by hypoosmolality, hypervolemia, or hypertension. These osmotic and hemodynamic influences are mediated by neuronal afferents that originate in separate osmoreceptors or baroreceptors but ultimately converge to act on ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198600087-00017
更新日期:1986-01-01 00:00:00
abstract::Imipramine, amitriptyline, mianserine, maprotiline, and trazodone are five widely used antidepressant drugs with different chemical structures. Imipramine and amitriptyline are tricyclics, mianserine and maprotiline are tetracyclics, and trazodone is a triazolopyridine derivative. We studied the effects of these drugs...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199810000-00004
更新日期:1998-10-01 00:00:00
abstract::The quantitative receptor autoradiographic method we used revealed that specific [125I]endothelin-1 ([125I]ET-1) binding sites are highly concentrated in the choroid plexus (ChP), subfornical organ (SFO), lacunosum molecular layer of the hippocampus (LMol), and granular layer of the cerebellum (GC) of the rat brain. [...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00037
更新日期:1991-01-01 00:00:00
abstract::We previously reported that i.v. DAMGO (Tyr-D-Ala-Gly-NMePhe-Gly-ol), a selective mu-opioid agonist, causes an increase in blood pressure with no change in heart rate in unanesthetized sheep and subsequently demonstrated that DAMGO attenuates baroreflex-mediated bradycardia. To determine the site and mechanism by whic...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200002000-00014
更新日期:2000-02-01 00:00:00
abstract::To assess dose-related effects of enalapril, we treated eight hospitalized hypertensive patients receiving constant sodium intake with incremental doses of this new angiotensin converting-enzyme blocking drug. After a few days of placebo treatment, enalapril was given in single daily doses, starting with 1.25 mg and i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198600081-00006
更新日期:1986-01-01 00:00:00
abstract::Hypertension is a well-known risk factor that predisposes to the development of left ventricular hypertrophy, coronary flow abnormalities, and systolic and diastolic dysfunction. This complex of abnormalities is known as hypertensive heart disease and eventually leads to heart failure. Structural lesions underlying th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199800003-00003
更新日期:1998-01-01 00:00:00
abstract::The long QT-related arrhythmia torsades de pointes (TdP) can arise with mutations in HERG and during treatment with drugs that block cardiac I Kr, the current encoded by HERG. Multiple test systems have been used to assess drug block of I Kr. This study evaluated the I Kr blocking potency of a series of antiarrhythmic...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200111000-00010
更新日期:2001-11-01 00:00:00