Abstract:
:Calcific aortic valve sclerosis involves inflammatory processes and occurs preferentially on the aortic side of endothelialized valve leaflets. Although the endothelium is recognized to play critical roles in focal vascular sclerosis, the contributions of valvular endothelial phenotypes to aortic valve sclerosis and side-specific susceptibility to calcification are poorly understood. Using RNA amplification and cDNA microarrays, we identified 584 genes as differentially expressed in situ by the endothelium on the aortic side versus ventricular side of normal adult pig aortic valves. These differential transcriptional profiles, representative of the steady state in vivo, identify globally distinct endothelial phenotypes on opposite sides of the aortic valve. Several over-represented biological classifications with putative relevance to endothelial regulation of valvular homeostasis and aortic-side vulnerability to calcification were identified among the differentially expressed genes. Of note, multiple inhibitors of cardiovascular calcification were significantly less expressed by endothelium on the disease-prone aortic side of the valve, suggesting side-specific permissiveness to calcification. However, coexisting putative protective mechanisms were also expressed. Specifically, enhanced antioxidative gene expression and the lack of differential expression of proinflammatory molecules on the aortic side may protect against inflammation and lesion initiation in the normal valve. These data implicate the endothelium in regulating valvular calcification and suggest that spatial heterogeneity of valvular endothelial phenotypes may contribute to the focal susceptibility for lesion development.
journal_name
Circ Resjournal_title
Circulation researchauthors
Simmons CA,Grant GR,Manduchi E,Davies PFdoi
10.1161/01.RES.0000161998.92009.64subject
Has Abstractpub_date
2005-04-15 00:00:00pages
792-9issue
7eissn
0009-7330issn
1524-4571pii
01.RES.0000161998.92009.64journal_volume
96pub_type
杂志文章abstract:RATIONALE:Chronic elevation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels has been associated with cardiac remodeling and cardiac hypertrophy. However, enhancement of particular aspects of cAMP/protein kinase A signaling seems to be beneficial for the failing heart. cAMP is a pleiotropic second messenger with t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.305892
更新日期:2015-09-25 00:00:00
abstract::Although isoform-selective translocation of protein kinase C (PKC) epsilon appears to play an important role in the late phase of ischemic preconditioning (PC), the mechanism(s) responsible for such translocation remains unclear. Furthermore, the signaling pathway that leads to the development of late PC after exogeno...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.5.587
更新日期:1999-03-19 00:00:00
abstract::Vascular endothelial growth factor (VEGF) expression is upregulated by hypoxia-inducible factor-1 (HIF-1) in ischemic tissues and growing tumors. Normally, HIF-1 activity depends on the amount of HIF-1alpha subunit, which is tightly regulated by the oxygen tension. In the myocardium, VEGF expression has been shown to ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0202.104923
更新日期:2002-02-08 00:00:00
abstract::A variety of delivery systems have been used to genetically modify vascular endothelial cells and smooth muscle cells (SMCs), but currently available systems suffer from either inefficient in vivo gene transfer, transient episomal vector expression, or significant immune responses and inflammation. In the present stud...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::We previously have shown that alpha-adrenergic stimulation of canine Purkinje fibers and rat ventricle decreases automaticity. Experiments on rat ventricular myocytes in tissue culture have suggested that the decrease in automaticity induced by alpha-adrenergic stimulation depends on the development of sympathetic inn...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.2.315
更新日期:1988-02-01 00:00:00
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
doi:10.1161/01.res.45.2.267
更新日期:1979-08-01 00:00:00
abstract:RATIONALE:Cryptogenic strokes, those of unknown cause, have been estimated as high as 30% to 40% of strokes. Inflammation has been suggested as a critical etiologic factor. However, there is lack of experimental evidence. OBJECTIVE:In this study, we investigated inflammation-associated stroke using a mouse model that ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.310349
更新日期:2017-12-08 00:00:00
abstract::Fetal ventricular performance has been considered limited because ventricular output does not increase with rapid volume expansion above mean left atrial pressures (mLAPs) of 5-7 mm Hg. To explore relations between preload, afterload, and stroke volume (SV) in the fetal left ventricle, we instrumented 126-129 days ges...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.1.127
更新日期:1989-07-01 00:00:00
abstract::We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) mice. We o...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000242559.42077.22
更新日期:2006-09-15 00:00:00
abstract::Astrocyte signals can modulate arteriolar tone, contributing to regulation of cerebral blood flow, but specific intercellular communication mechanisms are unclear. Here we used isolated cerebral arteriole myocytes, astrocytes, and brain slices to investigate whether carbon monoxide (CO) generated by the enzyme heme ox...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.164145
更新日期:2008-02-01 00:00:00
abstract::Power ratios were derived from the principle of ultrasonic Doppler velocimetry to determine a ratio of the volume of vortices to the total vessel volume under the ultrasonic beam. This ratio also equals the ratio of the cross-sectional area of vortices to the vessel lumen. In vitro pulsatile flow experiments were perf...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.1.166
更新日期:1990-07-01 00:00:00
abstract::Osteopontin (OPN) is a cytokine upregulated in diabetic vascular disease. To better understand its role in vascular remodeling, we assessed how OPN controls metalloproteinase (MMP) activation in aortic adventitial myofibroblasts (AMFs) and A7r5 vascular smooth muscle cells (VSMCs). By zymography, OPN and tumor necrosi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000227550.00426.60
更新日期:2006-06-23 00:00:00
abstract::Mechanical forces participate in morphogenesis from the level of individual cells to whole organism patterning. This article reviews recent research that has identified specific roles for mechanical forces in important developmental events. One well defined example is that dynein-driven cilia create fluid flow that de...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.108.175331
更新日期:2008-08-01 00:00:00
abstract::Vascular endothelial growth factors (VEGFs) and their receptors have emerged as central regulators of the angiogenic process. However, involvement of VEGF-B, one of these factors, in angiogenesis remains obscure. Mice received subcutaneous injection of Matrigel alone or Matrigel with human recombinant protein rhVEGF-B...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000081594.21764.44
更新日期:2003-07-25 00:00:00
abstract::Bone marrow-derived cells (BMCs) have been implicated as a modifiers of vascular growth either directly by transdifferentiation into endothelial cells (ECs) or indirectly through growth factor release. To examine these possibilities under physiological conditions, we developed a model of hypoxia-mediated angiogenesis ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000189259.69645.25
更新日期:2005-11-11 00:00:00
abstract::Mechanical overload elicits functional and structural adaptive mechanisms in cardiac muscle. Signaling pathways linked to integrin/cytoskeleton complexes may have a function in mediation of the effects of mechanical stimulus in myocardial cells. We investigated the tyrosine phosphorylation and the assembly of the mult...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.7.558
更新日期:2000-09-29 00:00:00
abstract::We investigated expression of the 5'-spliced isoform of smooth muscle myosin heavy chain (SM-MHC-B) in smooth muscle cells of cardiac vessels of the left ventricle of normotensive (Wistar-Kyoto) and spontaneously hypertensive rats of the stroke-prone strain by immunofluorescence microscopy. In parallel, liver and blad...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.2.204
更新日期:1998-07-27 00:00:00
abstract:RATIONALE:Aortic valve disease is a cell-mediated process without effective pharmacotherapy. CNP (C-type natriuretic peptide) inhibits myofibrogenesis and osteogenesis of cultured valve interstitial cells and is downregulated in stenotic aortic valves. However, it is unknown whether CNP signaling regulates aortic valve...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.311194
更新日期:2018-02-02 00:00:00
abstract::Matrix metalloproteinases (MMPs) include most major constituents of the arterial wall as substrates. A common promotor polymorphism (5A/6A) is associated with differences in MMP-3 (stromelysin-1) activity, and associations with certain forms of vascular disease have been shown. This study investigated whether the MMP-...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000076891.24317.CA
更新日期:2003-06-13 00:00:00
abstract::We studied the specificity of uptake of infarct-imaging agents for reversibly or irreversibly injured myocardium independently of blood flow by using intact beating fetal mouse hearts in organ culture. Reversible injury resulted from deprivation of oxygen and glucose for 4 hours at 37 degrees C; irreversible injury, f...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.6.860
更新日期:1976-12-01 00:00:00
abstract::Cardiovascular dysfunction as a result of sepsis is the leading cause of death in the critically ill. Cardiomyocytes respond to infectious pathogens with a Toll-like receptor-initiated proinflammatory response in conjunction with a decrease in contractility, although the downstream events linking Toll-like receptor ac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.167544
更新日期:2008-05-23 00:00:00
abstract::The aim of this study was to determine whether prolonged loss of NO activity, in endothelial NO synthase knockout (eNOS(-/-)) mice, influences endothelin (ET) ETA receptor-mediated smooth muscle contraction and, if so, to define the underlying mechanism(s). In isolated endothelium-denuded abdominal aortas, contraction...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000224120.52792.10
更新日期:2006-06-09 00:00:00
abstract::Baroreceptor reflexes can be demonstrated during fetal life, but whether baroreceptors normally regulate fetal arterial pressure is unknown. This problem was addressed directly by measuring arterial pressure and analyzing its variation in eight unanesthetized fetal lambs throughout the last third of gestation, and com...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.5.580
更新日期:1983-05-01 00:00:00
abstract:RATIONALE:Wnt signaling regulates key aspects of diabetic vascular disease. OBJECTIVE:We generated SM22-Cre;LRP6(fl/fl);LDLR(-/-) mice to determine contributions of Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6) in the vascular smooth muscle lineage of male low-density lipoprotein receptor-nu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.306712
更新日期:2015-07-03 00:00:00
abstract::Electrical activity of enzymatically isolated, smooth muscle cells from hog carotid arteries was recorded under current clamp and voltage clamp. Under the experimental conditions, membrane potential usually was not stable, and spontaneous hyperpolarizing transients of approximately 100-msec duration were recorded. The...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.3.708
更新日期:1989-09-01 00:00:00
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
doi:10.1161/01.res.39.3.314
更新日期:1976-09-01 00:00:00
abstract::Anisotropic impulse conduction was studied in neonatal rat heart cell monolayers produced by culturing cells on a growth-directing substrate of collagen. Monolayers consisting of parallel-oriented cells without visible intercellular clefts were selected for experiments; cell lengths and widths were 65.8 +/- 12.5 and 1...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.3.591
更新日期:1994-09-01 00:00:00
abstract:RATIONALE:7-Ketocholesterol (7-KC), a form of cholesterol oxidation product, plays an essential role in the atherogenesis in animal models. OBJECTIVE:We sought to determine the association of circulating 7-KC with clinical cardiovascular outcomes and total mortality in patients with stable coronary artery disease. ME...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.311049
更新日期:2017-05-12 00:00:00
abstract::We have previously shown that a cryoactivatable inactive form of renin, which we have tentatively termed prorenin, occurs in human plasma. Plasma prorenin is measured by subtracting the endogenous plasma renin activity (PRA) from the total renin activity measured after cryoactivation. Cryoactivation is accomplished by...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract:RATIONALE:Innate and adaptive immune responses alter numerous homeostatic processes that are controlled by nuclear hormone receptors. NR4A1 is a nuclear receptor that is induced in vascular pathologies, where it mediates protection. OBJECTIVE:The underlying mechanisms that regulate the activity of NR4A1 during vascula...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.258814
更新日期:2012-04-13 00:00:00