A5107835989- Nitric Oxide and Endothelin Effects
- Angiogenesis and VEGF in Cancer
- Receptor Mechanisms and Signaling
- Acute Ischemic Stroke Management
- Neuropeptides and Animal Physiology
- Neurological Disease Mechanisms and Treatments
- Adipose Tissue and Metabolism
- Heart Rate Variability and Autonomic Control
- Cardiac Ischemia and Reperfusion
- Eicosanoids and Hypertension Pharmacology
- Cerebrovascular and Carotid Artery Diseases
- Pharmacological Effects and Assays
- Renin-Angiotensin System Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Congenital heart defects research
- Pregnancy and preeclampsia studies
- Renal and Vascular Pathologies
- Cardiovascular Health and Disease Prevention
- Cancer-related molecular mechanisms research
- Hormonal Regulation and Hypertension
- Cancer, Hypoxia, and Metabolism
- Hormonal and reproductive studies
- Cardiovascular and exercise physiology
- Cerebrovascular and genetic disorders
- Molecular Biology Techniques and Applications
University of North Carolina at Chapel Hill
2015-2025
Deventer Ziekenhuis
2024
Erasmus MC
2024
Taipei Medical University
2017
Imaging Center
2017
Indiana University School of Medicine
2010-2015
Amsterdam UMC Location Vrije Universiteit Amsterdam
2013-2014
University Medical Center
2014
Ludwig-Maximilians-Universität München
2014
Northeast Ohio Medical University
2014
Severity of stroke varies widely among individuals. Whether differences in the extent native (preexisting) pial collateral circulation exist and contribute to this variability is unknown. We addressed these questions probed for potential genetic contributions using morphometric analysis 15 inbred mouse strains recently shown exhibit wide infarct volume. Morphometrics were determined unligated left hemisphere (for collaterals) ligated right remodeled 6 days after permanent middle cerebral...
Aging is a major risk factor for increased ischemic tissue injury. Whether collateral rarefaction and impaired remodeling contribute to this unknown. We quantified the number diameter of native collaterals their in 3-, 16-, 24-, 31-month-old mice.Aging caused an "age-dose-dependent" greater drop perfusion immediately after femoral artery ligation, followed by diminished recovery flow increase These effects were associated with decline number, diameter, remodeling. Angiogenesis was also...
Substantial variability exists in collateral density and ischemia-induced growth among species. To begin to probe the underlying mechanisms, which are unknown, we characterized two mouse strains with marked differences both parameters. Immediately after femoral artery ligation, foot perfusion were lower BALB/c than C57BL/6 (P < 0.05 here below), suggesting fewer pre-existing collaterals. This was confirmed angiography immunohistochemistry (approximately 35% collaterals BALB/c's thigh)....
We sought to identify potentially modifiable determinants associated with variability in leptomeningeal collateral status patients acute ischemic stroke. Data are from the Keimyung Stroke Registry. Consecutive M1 segment middle cerebral artery ± intracranial internal carotid occlusions on baseline computed tomographic angiography (CTA) May 2004 July 2009 were included. Baseline and follow-up imaging was analyzed blinded all clinical information. Two raters assessed collaterals CTA by...
The density of native (preexisting) collaterals and their capacity to enlarge into large conduit arteries in ischemia (arteriogenesis) are major determinants the severity tissue injury occlusive disease. Mechanisms directing arteriogenesis remain unclear. Moreover, nothing is known about how form healthy tissue. Evidence suggests vascular endothelial growth factor (VEGF), which important embryonic patterning ischemic angiogenesis, may contribute collateral formation arteriogenesis....
The purpose of this study was to determine whether both alpha 1- and 2-adrenergic receptors exist on vascular smooth muscle microvessels adrenergic constriction anatomically distinct microvascular segments is differentially subserved by either receptor subtype. cremaster skeletal anesthetized rats acutely denervated suspended in a Krebs bath containing cocaine, normetanephrine, propranolol block uptake1, uptake2, beta-receptors, respectively. Intravital microscopy used large distributing...
The collateral circulation is tissue- and life-saving in obstructive arterial disease. Disappointing outcomes clinical trials aimed at augmenting growth highlight the need for greater understanding of biology.The role endothelial nitric oxide synthase (eNOS) forming native (preexisting) collaterals remodeling disease are unknown or controversial issues, respectively.We compared healthy tissue after femoral artery ligation (FAL) wild-type eNOS-knockout (KO) mice. Perfusion FAL fell further...
Rationale: The density of native (preexisting) collaterals varies widely and is a significant determinant variation in severity stroke, myocardial infarction, peripheral artery disease. However, little known about mechanisms responsible for formation the collateral circulation healthy tissues. Objective: We previously found that vascular endothelial growth factor (VEGF) expression causes differences newborn adult mice. Herein, we sought to determine collaterogenesis embryo role VEGF this...
The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and ability precisely manipulate genome. Despite importance genetics quality control (QC) not standardized, lack cost-effective, informative, robust platforms. Genotyping arrays are standard tools research remain an attractive alternative even era high-throughput whole-genome sequencing. Here, we describe content performance a new iteration...
Background&Objectives: It remains unclear why unilateral proximal carotid artery occlusion (UCAO) causes benign oligemia, without progressing to cerebral infarction, in mice, yet leads a wide variety of outcomes (asymptomatic-to-death) humans. We hypothesized that inhibition nitric oxide synthase (NOS) both transforms UCAO-mediated oligemia into full infarction and expands preexisting infarction. Methods: Using 900 we i) investigated stroke-related effects single intraperitoneal dose the...
α 1 -Adrenoceptor–dependent proliferation of vascular smooth muscle cells (VSMCs) is strongly augmented by injury, and may contribute to intimal growth lumen loss. Because reactive oxygen species (ROS) are increased injury have been implicated as second messengers in VSMCs, we investigated the role ROS catecholamine-induced VSMC growth. Rat aortae were isolated 4 days after balloon maintained organ culture under circumferential wall tension, exposed agents for 48 hours. The antioxidants...
Abstract Tendon cells receive mechanical signals from the load bearing matrices. The response to stimulation is crucial for tendon function. However, overloading may deteriorate extracellular matrix integrity by activating intrinsic factors such as metalloproteinases (MMPs) that trigger destruction. We hypothesized loading might induce interleukin‐1beta (IL‐1β) in cells, which can MMPs, and ATP inhibit load‐inducible gene expression. Human isolated flexor digitorum profundus tendons (FDPs)...
Our previous studies in rat skeletal muscle have determined that neural constriction of large arterioles, which regulate blood flow and peripheral resistance, is mediated by alpha 1-adrenoceptors, whereas small determine effective capillary density, depend on 2-receptors. During physical exercise, metabolic vasodilators from contracting oppose vasoconstriction. By mechanisms are not understood, adrenergic arterioles particularly sensitive to inhibition during imbalances oxygen supply versus...
Rat aorta smooth muscle cells which express all three α1-adrenoreceptors (α1A, α1B and α1D) were used to determine the effect of stimulation α1-adrenergic receptor subtypes on cell growth. "Combined"α1-adrenoreceptor subtype with norepinephrine alone caused a concentration-dependent, prazosin-sensitive increase in protein content synthesis: 48 h at 1 μM increased 216 ± 40% time-matched controls (p = 0.008) RNA 140 13% 0.03); synthesis 167 < 0.01) after 24 h. Stimulation plus selective...
The extent (density and diameter) of the native (preexisting) collateral circulation in healthy tissues capacity collaterals to enlarge/remodel obstructive arterial disease are important determinants ischemic injury. Evidence suggests that these parameters vary widely from yet-to-be-identified genetic environmental factors. Recently, a locus on chromosome 7 was linked less recovery perfusion after femoral artery ligation BALB/c A/J versus C57BL/6 mouse strains. Moreover, evidence suggested...
Excess soluble fms-like tyrosine kinase 1 (sFlt-1) of vascular endothelial growth factor receptor secreted from the placenta causes pre-eclampsia–like features by antagonizing signaling, which can lead to reduced nitric oxide synthase (eNOS) activity; effect this concomitant decrease in eNOS activity is unknown. We tested whether occurring female mice lacking aggravates phenotype induced increased sFlt-1. Untreated eNOS-deficient had higher BP than wild-type mice. Adenovirus-mediated...
Rationale: Collaterals are arteriole-to-arteriole anastomoses that connect adjacent arterial trees. They lessen ischemic tissue injury by serving as endogenous bypass vessels when the trunk of 1 tree becomes narrowed vascular disease. The number and diameter (“extent”) native (preexisting) collaterals, plus their amount lumen enlargement (growth/remodeling) in occlusive disease, show remarkably wide variation among inbred mouse strains (eg, C57BL/6 BALB/c), resulting large differences models...
The extent (number and diameter) of collateral vessels varies widely is a major determinant, along with arteriogenesis (collateral remodeling), variation in severity tissue injury after large artery occlusion. Differences genetic background underlie the majority mice, through alterations collaterogenesis (embryonic formation). In brain other tissues, ≈80% among different mouse strains has been linked to region on chromosome 7. We recently used congenic (CNG) fine mapping C57BL/6 (B6, high...