Browsing by Author "Giles, Wayne R."
Now showing 1 - 15 of 15
Results Per Page
Sort Options
Item Open Access A murine model of emery-dreifuss muscular dystrophy(2003) Grattan, Michael James; Giles, Wayne R.Item Open Access Aminophylline effects on ventilation and respiratory muscles(2008) Jagers, Jenny V.; Giles, Wayne R.; Easton, PaulItem Open Access Balance rehabilitation in multiple sclerosis: effect of a commercially available virtual reality based videogame(2011) Korsbrek, Erin Brooks; Giles, Wayne R.Item Open Access Bioinductive Effects of Acellular Biologic Scaffolds Promote Adaptive Cardiac Repair Following Myocardial Infarction(2018-09-17) Svystonyuk, Daniyil A.; Fedak, Paul; Tibbles, Lee Anne; Duff, Henry J.; Giles, Wayne R.Ischemic injury may lead to structural remodeling and progressive loss of function, resulting in eventual decompensation to heart failure. Acellular biologic ECM scaffolds retain their native 3-D architecture along with a profile of bioactive constituents that may be leveraged surgically to support myocardial healing. In a proof of concept study, we have previously identified FGF-2 bound to the acellular ECM scaffolds. As such, we hypothesized that FGF-2-dependent bioinductive signaling from surgically implanted acellular scaffolds may attenuate maladaptive structural remodeling and improve functional recovery post-myocardial infarction (MI). First, we observed that FGF-2 has potent anti-fibrotic properties that limited human cardiac fibroblast activation and cell-mediated ECM dysregulation in an in vitro 3-D model. Biochemical characterization showed that ECM scaffolds intact with bioactive constituents released FGF-2 under passive conditions. In a rodent model of myocardial infarction, animals that received intact ECM scaffolds following ischemic injury showed improved functional recovery with evidence of new blood vessel assembly underlying the implantation site. The functional benefits and neovascularization processes were absent in animals that received inactivated scaffolds where FGF-2 bioavailability was limited. The FGF-2-dependent bioinductive effect favorably targeted cardiac fibroblasts, who demonstrated phenotypic plasticity away from a pro-fibrotic phenotype and towards a pro-reparative vasculogenic phenotype. The anti-fibrotic effects of acellular ECM scaffold-derived FGF-2 were consistent with our in vitro studies, however the phenotypic change was unexpected. The redirection in fibroblast phenotype was associated with a modified cardiac scar characterized by a pro-vasculogenic paracrine microenvironment capable of supporting new blood vessel formation and attenuating fibrotic processes. Once again, limiting FGF-2 bioavailability from the ECM scaffolds or blocking FGF receptors in cardiac fibroblasts abolished the induced vasculogenic phenotype. We extended our observations to human subjects where biologic scaffolds were surgically implanted at the site of ischemic injury as an adjunct to standard surgical revascularization. In patients with severe microvascular obstruction and concomitant cardiac dysfunction, acellular biologic scaffolds improved global scar volume and stimulated regional recovery of resting myocardial perfusion. In summary, acellular biologic scaffolds stimulate myocardial healing following ischemic injury through FGF-2-dependent bioinductive signaling that modifies the ischemic scar to support neovascularization, adaptive remodeling, and functional recovery.Item Open Access Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review(2024-12-27) Suzuki, Yoshiaki; Giles, Wayne R.; Zamponi, Gerald W.; Kondo, Rubii; Imaizumi, Yuji; Yamamura, HisaoAbstract Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) act together to regulate blood pressure and systemic blood flow by appropriately adjusting blood vessel diameter in response to biochemical or biomechanical stimuli. Ion channels that are expressed in these cells regulate membrane potential and cytosolic Ca2+ concentration ([Ca2+]cyt) in response to such stimuli. The subsets of these ion channels involved in Ca2+ signaling often form molecular complexes with intracellular molecules via scaffolding proteins. This allows Ca2+ signaling to be tightly controlled in localized areas within the cell, resulting in a balanced vascular tone. When hypertensive stimuli are applied to blood vessels for extended periods, gene expression in these vascular cells can change dramatically. For example, alteration in ion channel expression often induces electrical remodeling that produces a depolarization of the membrane potential and elevated [Ca2+]cyt. Coupled with endothelial dysfunction blood vessels undergo functional remodeling characterized by enhanced vasoconstriction. In addition, pathological challenges to vascular cells can induce inflammatory gene products that may promote leukocyte infiltration, in part through Ca2+-dependent pathways. Macrophages accumulating in the vascular adventitia promote fibrosis through extracellular matrix turnover, and cause structural remodeling of blood vessels. This functional and structural remodeling often leads to chronic hypertension affecting not only blood vessels, but also multiple organs including the brain, kidneys, and heart, thus increasing the risk of severe cardiovascular events. In this review, we outline recent advances in multidisciplinary research concerning Ca2+ signaling in VSMCs and ECs, with an emphasis on the mechanisms underlying functional and structural vascular remodeling.Item Open Access Item Open Access Electrophysiological and contractile evaluation of rabbit and rat ventricular myocytes in short term culture(1992) Juhasz, Alexander E.; Giles, Wayne R.Item Open Access Electrophysiological and mechanical measurements in human and rabbit atria(1987) Ilnicki, Teri; Giles, Wayne R.Item Restricted Electrophysiological effects of C-type natriuretic peptide in the heart and in the central nervous system: the role of the NPR-C receptor(2005) Rose, Robert Alan; Giles, Wayne R.C-type natriuretic peptide (CNP) is one member of a group of related peptide hormones, which also includes atrial and brain natriuretic peptides, that elicit a wide range of effects in vertebrates, including humans. The natriuretic peptide C receptor (NPR-C) is functionally linked to an inhibitory G protein (Gi) that inhibits adenylyl cyclase (via the a subunit) and activates phospholipase C (PLC; via the ~y subunit). This thesis describes novel electrophysiological effects of CNP in cardiac myocytes, fibroblasts , and hypothalamic neurons that are specifically mediated by NPR-C. In isolated bullfrog atrial myocytes CNP (1 o-8 M) significantly shortened the duration and decreased the amplitude of the action potential. CNP and the NPR-C selective agonist, cANF (10-8 M), significantly decreased the L-type Ca2 + current Clca(L)) without altering the inward rectifier K+ current indicating that CNP inhibits Ica(L) when it binds NPR-C. To explore the selectivity of CNP effects voltage clamp studies on isolated sinoatrial (SA) node myocytes were performed. In these myocytes CNP and cANF strongly inhibited isoproterenol-stimulated Ica(L) without altering another cAMP sensitive current, Ir. Measurement of EC Gs in Langendorff-perfused mouse hearts revealed the ability of CNP and cANF to decrease heart rate. A similar pattern of results was observed in magnocellular neurosecretory cells (MN Cs) of the hypothalamus. In these neurons, which are responsible for the release of vasopressin and oxytocin, CNP and cANF selectively inhibited Ica(L)· Another voltage gated Ca2+ current, Ica(T), was not modulated by CNP. The inhibition oflca(L) resulted in a decrease in MNC excitability and a shortening of action potential duration in these neurons. In isolated cardiac fibroblasts, CNP and cANF activated an outwardly rectifying current with an apparent reversal potential near O m V. This current was inhibited by the transient receptor potential (TRP) channel blockers Gd3 \ SKF 96365 and 2-APB. The response was also antagonized by the PLC antagonist U73122. Together, these results indicate that CNP activates a TRP channel in cardiac fibroblasts following the activation of PLC by the NPR-C receptor. These data provide the first description of electrophysiological effects of CNP that are mediated by NPR-C in the heart and the hypothalamus.Item Open Access Electrophysiology of isolated intracardiac parasympathetic neurons from bullfrog(1989) Tse, Amy M. W.; Giles, Wayne R.Item Open Access Functional analysis of the role of akaps in mammalian heart cell(2008) Thurston, Jackie Lee; Giles, Wayne R.Item Open Access Mathematical modeling of electronic interactions between human ventricular myoctyes and cardiac fibroblasts(2007) MacCannell, Andrew; Giles, Wayne R.Item Open Access Molecular and biophysical analysis of the delayed rectifer K+ current in bullfrog atrium(1998) Lowes, Vicki Louise; Giles, Wayne R.Item Open Access Respiration-induced changes in heart rate in humans(2004) Melashenko, Lara D.; Giles, Wayne R.; Poulin, Marc J.Item Open Access The Effects of ryanodine on the force-interval relation of rat cardiac muscle(1990) Sethi, Sujata; Giles, Wayne R.