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Publications (40)
Microvascular endothelial dysfunction is a strong predictor of future adverse cardiac events. We have previously shown that exposure to chronic estrogen induces microvascular endothelial dysfunction in isolated microvessels from otherwise healthy adults, with more extensive dysfunction exhibited in vessels from males. Further, we have demonstrated...
Red light (670 nm) energy controls vasodilation via the formation of a transferable endothelium-derived nitric oxide (NO)-precursor-containing substance, its intracellular traffic, and exocytosis. Here we investigated the underlying mechanistic effect of oxidative stress on light-mediated vasodilation by using pressure myography on dissected murine...
Risk for cardiovascular disease (CVD) is elevated in individuals assigned female at birth and women of trans experience (assigned male at birth) undergoing long-term estrogen therapy (e.g. contraception, gender-affrmation). We have previously shown that chronic estrogen treatment induces microvascular endothelial dysfunction in human arterioles col...
Despite the well-known damaging effects of elevated intracellular ceramides on human microvascular function, our recent work has shown that inhibition of ceramide formation through neutral sphingomyelinase (NSmase) promotes endothelial dysfunction in arterioles from healthy adults, manifested as endothelial production of hydrogen peroxide (H 2 O 2...
We have previously established that 670 nm energy induces relaxation of blood vessels via an endothelium derived S -nitrosothiol (RSNO) suggested to be embedded in vesicles. Here, we confirm that red light facilitates the exocytosis of this vasodilator from cultured endothelial cells and increases ex vivo blood vessel diameter. Ex vivo pressurized...
Background
Elevated plasma ceramides and microvascular dysfunction both independently predict adverse cardiac events. Despite the known detrimental effects of ceramide on the microvasculature, evidence suggests that activation of the shear-sensitive, ceramide-forming enzyme NSmase (neutral sphingomyelinase) elicits formation of vasoprotective nitri...
Compared to cis-males and females, risk for cardiovascular disease (CVD) is elevated in trans-females undergoing estrogen-containing gender affirming therapy. We have previously shown that continuous estrogen treatment of arterioles from healthy adults assigned male at birth promotes microvascular endothelial dysfunction, however the mechanism thro...
Despite the known damaging effects of elevated intracellular ceramides on human microvascular function, our recent work showed that loss of ceramide-formation through neutral sphingomyelinase (NSmase) promotes endothelial dysfunction in arterioles from healthy adults. This presents as a switch in the endothelial-derived mediator responsible for eli...
Background
Elevated plasma ceramides independently predict adverse cardiac events and we have previously shown that exposure to exogenous ceramide induces microvascular endothelial dysfunction in arterioles from otherwise healthy adults (0-1 risk factors for heart disease). However, evidence also suggests that activation of the shear-sensitive, cer...
We have previously shown that ceramide can increase production of vasoprotective nitric oxide (NO) in arterioles from healthy adults (0-1 risk factors for coronary artery disease; CAD) and elicit acute dilation. This process is dependent on ceramide’s conversion to sphingosine-1-phosphate (S1P), a well-established activator of endothelial NO-syntha...
Nitric oxide dependent vasodilation is an effective mechanism for restoring blood flow to ischemic tissues. Previously, we established an ex vivo murine model whereby red light (670 nm) facilitates vasodilation via an endothelium derived vasoactive species which contains a functional group that can be reduced to nitric oxide. In the present study w...
Preeclampsia is a serious pregnancy disorder which in extreme cases may lead to maternal and fetal injury or death. Preexisting conditions which increase oxidative stress, e.g., hypertension and diabetes, increase the mother’s risk to develop preeclampsia. Previously, we established that when the extracellular matrix is exposed to oxidative stress,...
Introduction
Peripheral artery disease (PAD) is a highly morbid condition in which impaired blood flow to the limbs leads to pain and tissue loss. Previously we identified 670 nm electromagnetic energy (R/NIR) to increase nitric oxide levels in cells and tissue. NO elicits relaxation of smooth muscle (SMC) by stimulating potassium efflux and membra...
Preeclampsia is a leading cause of maternal morbidity and mortality worldwide, complicating 2-8% of pregnancies. The etiology of PE is poorly understood, the role of placental extracellular matrix (pECM) in PE is understudied. Extravillous trophoblasts (HTR8/svneo) and pECM are crucial in placental blood vessel formation, including spiral arteries....
Red light (670 nm) promotes ex vivo dilation of blood vessels in a nitric oxide (NO) dependent, but eNOS independent manner by secreting a quasi-stable and transferable vasoactive substance with the characteristics of S-nitrosothiols (RSNO) from the endothelium. In the present work we establish that 670 nm light mediated vasodilation occurs in vivo...
In previous studies we demonstrated endothelial dependent vasodilation at 670nm red/near infrared light (670nm light) in healthy vessels and db/db mice related to S‐nitrosothiol release. Furthermore, the bath solution from intact 670nm light stimulated vessels could dilate 670nm light naïve vessels in a NO dependent manner. Therefore, we propose th...
Introduction
In our previous work we demonstrated the importance of altered extracellular matrix (ECM) in disease processes and how treatment with 670 nm LLLT can restore cell behavior.
Objective
Of this study focuses on the signaling properties of altered ECM in preeclampsia, its contribution to preeclampsia, and the possibility of a novel therap...
There is significant therapeutic advantage of nitric oxide synthase (NOS) independent nitric oxide (NO) production in maladies where endothelium, and thereby NOS, is dysfunctional. Electromagnetic radiation in the red and near infrared region has been shown to stimulate NOS-independent but NO-dependent vasodilation, and thereby has significant ther...
Far red/near infrared (R/NIR) energy is a novel therapy, but its mechanism of action is poorly characterized. Cytochrome c oxidase (Cco) of the mitochondrial electron transport chain is considered the primary photoacceptor for R/NIR to photolyze a putative heme nitrosyl in Cco to liberate free nitric oxide (NO). We previously observed R/NIR light d...
Peripheral artery disease (PAD) is a morbid condition whereby ischemic peripheral muscle causes pain and tissue breakdown. Interestingly, PAD risk factors, e.g. diabetes mellitus, cause endothelial dysfunction secondary to decreased nitric oxide (NO) levels, which could explain treatment failures. Previously, we demonstrated 670nm light (R/NIR) inc...
Introduction: Over 8 million Americans are treated for peripheral artery disease (PAD), i.e. intermittent claudication, impaired wound healing, and critical limb ischemia. Endothelial dysfunction of the microcirculation is a potential mechanism for the pathogenesis of PAD because risk factors for PAD- age, hypertension, atherosclerosis, diabetes me...
Over 8 million Americans are treated for symptoms related to peripheral artery disease (PAD). Risk factors for PAD have been directly related to a reduction in NOS expression and NO production. Light irradiation at the far red/near infrared region (670 nm (R/NIR)) can stimulate angiogenesis by increasing NO independent of NOS through release of NO...
Over 8 million Americans are treated for symptoms related to peripheral artery disease (PAD), such as intermittent claudication, impaired wound healing, and critical limb ischemia. We have shown light irradiation at the far red/near infrared region (670 nm (R/NIR)) can stimulate angiogenesis by increasing NO independent of NOS through release of NO...
Mitochondrial dysfunction is associated with various forms of lung injury and disease that also involve alterations in pulmonary endothelial permeability, but the relationship, if any, between the two is not well understood. This question was addressed by perfusing the isolated intact rat lung with a buffered physiological saline solution in the ab...
Previous studies showed that coenzyme Q(1) (CoQ(1)) reduction on passage through the rat pulmonary circulation was catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex I, but that NQO1 genotype was not a factor in CoQ(1) reduction on passage through the mouse lung. The aim of the present study was to evaluate the complex I...
Treatment of bovine pulmonary arterial endothelial cells in culture with the phase II enzyme inducer sulforaphane (5μM, 24h; sulf-treated) increased cell-lysate NAD(P)H:quinone oxidoreductase (NQO1) activity by 5.7 ± 0.6 (mean ± SEM)-fold, but intact-cell NQO1 activity by only 2.8 ± 0.1-fold compared to control cells. To evaluate the hypothesis tha...
The quinones duroquinone (DQ) and coenzyme Q(1) (CoQ(1)) and quinone reductase inhibitors have been used to identify reductases involved in quinone reduction on passage through the pulmonary circulation. In perfused rat lung, NAD(P)H:quinone oxidoreductase 1 (NQO1) was identified as the predominant DQ reductase and NQO1 and mitochondrial complex I...
One pulmonary endothelial metabolic function is reduction of blood borne redox compounds via NQO1, wherein phase II enzyme induction is a potential means to optimize this function. However, a threshold above which increases in NQO1 activity do not support increases in NQO1 substrate toxicity is seen in other cell types. The goal of this study was t...
The goal was to determine whether endogenous cytosolic NAD(P)H:quinone oxidoreductase 1 (NQO1) preferentially uses NADPH or NADH in intact pulmonary arterial endothelial cells in culture. The approach was to manipulate the redox status of the NADH/NAD(+) and NADPH/NADP(+) redox pairs in the cytosolic compartment using treatment conditions targeting...
The exogenous quinone, CoQ 1 , is reduced predominately via mitochondrial complex I (CI) in intact, cultured bovine pulmonary arterial endothelial cells (PAECs), wherein the hydroquinone (CoQ 1 H 2 ) product can be oxidized at complex III or appear in the extracellular medium. We hypothesized that insofar as CoQ 1 is a homolog of the endogenous CI...
NQO1 is a phase II antioxidant enzyme induced in PAEC by oxidative stress. Since isolated NQO1 utilizes either NADH or NADPH as electron donors, we asked whether either donor was preferentially utilized by NQO1 in intact calf PAEC. Intact PAEC NQO1 activity was measured using duroquinone (DQ) as the electron acceptor and cell pyridine nucleotide le...
The objective was to determine the impact of intact normoxic and hyperoxia-exposed (95% O(2) for 48 h) bovine pulmonary arterial endothelial cells in culture on the redox status of the coenzyme Q(10) homolog coenzyme Q(1) (CoQ(1)). When CoQ(1) (50 microM) was incubated with the cells for 30 min, its concentration in the medium decreased over time,...
The objective of this study was to examine the impact of chronic hyperoxic exposure (95% O2 for 48 h) on intact bovine pulmonary arterial endothelial cell redox metabolism of 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ). DQ or durohydroquinone (DQH2) was added to normoxic or hyperoxia-exposed cells in air-saturated medium, and the medium...
