A5078813192- Connexins and lens biology
- Sodium Intake and Health
- Heme Oxygenase-1 and Carbon Monoxide
- Heart Rate Variability and Autonomic Control
- Hormonal Regulation and Hypertension
- Nitric Oxide and Endothelin Effects
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Biochemical effects in animals
- Physiological and biochemical adaptations
- Neuroscience of respiration and sleep
- Ion Channels and Receptors
- High Altitude and Hypoxia
- Blood Pressure and Hypertension Studies
- Renin-Angiotensin System Studies
- Erythrocyte Function and Pathophysiology
- Circadian rhythm and melatonin
- Renal and Vascular Pathologies
- Olfactory and Sensory Function Studies
- Cancer-related molecular mechanisms research
- Heat shock proteins research
- Cardiovascular Disease and Adiposity
- Animal Behavior and Reproduction
- Stress Responses and Cortisol
- Mosquito-borne diseases and control
- Neurobiology and Insect Physiology Research
University of Virginia
2014-2022
University of Pittsburgh
2019-2022
Clinical Research Management
2020
Cardiovascular Research Center
2015-2018
Carter Center
2017
Tufts Medical Center
2017
La Trobe University
2017
Dalian Medical University
2016
SRI International
2016
Washington University in St. Louis
2016
Abstract Inflammatory cell recruitment to local sites of tissue injury and/or infection is controlled by a plethora signalling processes influencing cell-to-cell interactions between the vascular endothelial cells (ECs) in post-capillary venules and circulating leukocytes. Recently, ATP-sensitive P 2 Y purinergic receptors have emerged as downstream regulators EC activation inflammation. However, mechanism(s) regulating cellular ATP release this response remains elusive. Here we report that...
The mosquito-borne Zika virus (ZIKV) is now recognized as a blood-borne pathogen, raising an important question about how the gets into human bloodstream. imminent threat of ZIKV epidemic to global blood supply also demands novel therapeutics stop transmission though transfusion.We intend characterize tropism for endothelial cells (ECs) and provide potential targets intervention.We conducted immunostaining, plaque assay, quantitative reverse transcription-polymerase chain reaction RNA...
The ATP-releasing channel Panx1 is specifically involved in blood pressure regulation by adrenergic signaling.
Background: Impaired endothelium-dependent vasodilation is a hallmark of obesity-induced hypertension. The recognition that Ca 2+ signaling in endothelial cells promotes has led to the hypothesis compromised during obesity, but underlying abnormality unknown. In this regard, transient receptor potential vanilloid 4 (TRPV4) ion channels are major influx pathway cells, and regulatory protein AKAP150 (A-kinase anchoring 150) enhances activity TRPV4 channels. Methods: We used...
Rationale: Resistant hypertension is a major health concern with unknown cause. Spironolactone an effective antihypertensive drug, especially for patients resistant hypertension, and considered by the World Health Organization as essential medication. Although spironolactone can act at mineralocorticoid receptor (MR; NR3C2), there increasing evidence of MR-independent effects spironolactone. Objective: Here, we detail unexpected discovery that Panx1 (pannexin 1) channels could be relevant in...
The proinflammatory cytokine IL-1β is a significant risk factor in cardiovascular disease that can be targeted to reduce major events. expression and release are tightly controlled by changes intracellular Ca2+ ([Ca2+]i), which has been associated with ATP purinergic signaling. Despite this, the mechanisms regulate these have not identified. pannexin 1 (Panx1) channels canonically implicated release, especially during inflammation. We examined Panx1 human umbilical vein endothelial cells...
Increasing prevalence of obesity and its associated risk with cardiovascular diseases demands a better understanding the contribution different cell types within this complex disease for developing new treatment options. Previous studies could prove fundamental role FTO (fat mass obesity-associated protein) obesity; however, functional is less understood.We identify endothelial as previously unknown central regulator both obesity-induced metabolic vascular alterations.We generated...
Objective— Several physiological stimuli activate smooth muscle cell (SMC) G q PCRs (G protein–coupled receptors) to cause vasoconstriction. As a protective mechanism against excessive vasoconstriction, SMC PCR stimulation invokes endothelial vasodilatory signaling. Whether Ca 2+ influx in cells contributes the regulation of PCR-induced vasoconstriction remains unknown. through TRPV4 (transient receptor potential vanilloid 4) channels is key regulator endothelium-dependent vasodilation. We...
A pathway underlying the TNFα-induced decrease in endothelial barrier function is found veins but not arteries.
Objective- Sympathetic nerve innervation of vascular smooth muscle cells (VSMCs) is a major regulator arteriolar vasoconstriction, resistance, and blood pressure. Importantly, α-adrenergic receptor stimulation, which uniquely couples with Panx1 (pannexin 1) channel-mediated ATP release in resistance arteries, also requires localization to membrane caveolae. Here, we test whether Cav1 (caveolin-1) promotes channel function (stimulus-dependent adrenergic vasoconstriction) important for...
Abstract Resistance artery vasodilation in response to hypoxia is essential for matching tissue oxygen and demand. In hypoxia, erythrocytic hemoglobin tetramers produce nitric oxide through nitrite reduction. We hypothesized that the alpha subunit of expressed endothelium also facilitates reduction proximal smooth muscle. Here, we create two mouse strains test this: an endothelial-specific globin knockout (EC Hba1Δ/Δ) another with allele mutated prevent globin’s inhibitory interaction...
Red blood cell (RBC)-derived adenosine triphosphate (ATP) has been proposed as an integral component in the regulation of oxygen supply to skeletal muscle. In ex vivo settings RBCs have shown release ATP response a number stimuli, including stimulation adrenergic receptors. Further evidence suggested that from was dependent on activation adenylate cyclase (AC)/cyclic monophosphate (cAMP)-dependent pathways and involved pannexin 1 (Panx1) channel. Here we show express Panx1 confirm its...
The ability of hemoglobin to scavenge the potent vasodilator nitric oxide (NO) in blood has been well established as a mechanism vascular tone homeostasis. In endothelial cells, alpha chain (hereafter, globin) and NO synthase form macromolecular complex, providing sink for directly adjacent production source. We have developed an globin mimetic peptide (named HbαX) that displaces endogenous increases bioavailable vasodilation. Here we show that, vivo, HbαX administration capillary...
Renovascular hypertension is characterized by activation of the renin-angiotensin-aldosterone system, blunted natriuretic responses, and elevated sympathetic nerve activity. Excess dietary salt intake exaggerates arterial blood pressure (ABP) in multiple models experimental hypertension. The present study tested whether a high-salt diet exaggerated ABP vascular dysfunction 2-kidney, 1-clip (2K1C) murine model. Male C57BL/6J mice (8-12 wk) were randomly assigned, fed 0.1% or 4.0% NaCl diet,...
The circadian cycle impacts sympathetic nerve activity (SNA), cardiovascular hemodynamics, and renal function. Activation of sensory nerves by chemosensory mechanosensory stimuli reflexively changes efferent SNA arterial blood pressure (ABP) to maintain homeostasis. However, it is unclear what extent influences reflex ABP responses stimuli. Renal, splanchnic, lumbar intrarenal infusion bradykinin or capsaicin elevated pelvic were measured in male female Sprague-Dawley rats during nighttime...
Elevated renal afferent nerve (ARNA) activity or dysfunctional reno-renal reflexes via altered ARNA sensitivity contribute to hypertension and chronic kidney disease. These nerves contain mechano- chemosensitive fibers that respond ischemia, changes in intrarenal pressures, chemokines. Most studies have utilized various anesthetized preparations exclusively male animals characterize responses. Therefore, this study assessed the impact of anesthesia, sex, circadian period on responses...
Activation of renal sensory nerves by chemo- and mechanosensitive stimuli produces changes in efferent sympathetic nerve activity (SNA) arterial blood pressure (ABP). Anesthesia sex influence autonomic function cardiovascular hemodynamics, but it is unclear to what extent anesthesia impact SNA ABP responses stimuli. We measured renal, splanchnic, lumbar male female Sprague-Dawley rats during contralateral infusion capsaicin bradykinin or elevation pelvic pressure. Responses were evaluated...
Frigid temperatures of the Southern Ocean are known to be an evolutionary driver in Antarctic fish. For example, many fish have reduced red blood cell (RBC) concentration minimize vascular resistance. Via oxygen-carrying protein hemoglobin, RBCs contain vast majority body's iron, which is a limiting nutrient marine ecosystems. Since lower RBC levels also lead iron requirements, we hypothesize that low availability was additional speciation. Icefish family Channichthyidae extreme alteration...