6 results on '"Ongstad E"'
Search Results
2. Myocyte-fibroblast electrical coupling: the basis of a stable relationship?
- Author
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Ongstad, E. L., primary and Gourdie, R. G., additional
- Published
- 2011
- Full Text
- View/download PDF
3. Regulation of lymphatic capillary regeneration by interstitial flow in skin
- Author
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Goldman, J., Conley, K. A., Raehl, A., Bondy, D. M., Pytowski, B., Swartz, M. A., Rutkowski, J. M., Jaroch, D. B., and Ongstad, E. L.
- Subjects
Mice ,Skin/*blood supply/drug effects ,Lymphangiogenesis/drug effects/*physiology ,Animals ,Female ,Vascular Endothelial Growth Factor C/*administration ,Vascular Endothelial Growth Factor Receptor-3/metabolism ,Skin Physiology/drug effects ,Regeneration/drug effects/*physiology ,dosage ,Lymph Nodes/blood supply/drug effects/*physiology ,Inbred BALB C ,Lymphatic Vessels/drug effects/*physiology - Abstract
Decreased interstitial flow (IF) in secondary lymphedema is coincident with poor physiological lymphatic regeneration. However, both the existence and direction of causality between IF and lymphangiogenesis remain unclear. This is primarily because the role of IF and its importance relative to the action of the prolymphangiogenic growth factor vascular endothelial growth factor (VEGF)-C (which signals primarily through its receptor VEGFR-3) are poorly understood. To clarify this, we explored the cooperative roles of VEGFR-3 and IF in a mouse model of lymphangiogenesis in regenerating skin. Specifically, a region of lymphangiogenesis was created by substituting a portion of mouse tail skin with a collagen gel within which lymphatic capillaries completely regenerate over a period of 60 days. The relative importance of IF and VEGF-C signaling were evaluated by either inhibiting VEGFR-3 signaling with antagonistic antibodies or by reducing IF. In some cases, VEGF-C signaling was then increased with exogenous protein. To clarify the role of IF, the distribution of endogenous matrix metalloproteinases (MMPs) and VEGF-C within the regenerating region was determined. It was found that inhibition of either VEGFR-3 or IF suppressed endogenous lymphangiogenesis. Reduction of IF was found to decrease lymphatic migration and transport of endogenous MMP and VEGF-C through the regenerating region. Therapeutic VEGF-C administration restored lymphangiogenesis following inhibition of VEGFR-3 but did not increase lymphangiogenesis following inhibition of IF. These results identify IF as an important regulator of the pro-lymphangiogenic action of VEGF-C.
4. Association Between Soluble Lectinlike Oxidized Low-Density Lipoprotein Receptor-1 and Coronary Artery Disease in Psoriasis.
- Author
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Dey AK, Gaddipati R, Elnabawi YA, Ongstad E, Goyal A, Chung JH, Teague HL, Rodante JA, Sajja AA, Sorokin AV, Lateef SS, Aksentijevich M, Choi H, Reddy AS, Varghese NJ, Groenendyk J, Belur AD, Genovese L, Rivers JP, Lerman J, Kabbany MT, Harrington C, Ortiz J, Khalil N, Keel A, Baumer Y, Chen MY, Bluemke DA, Joshi AA, Kaplan MJ, Remaley AT, Playford MP, Karathanasis SK, Gelfand JM, Gupta R, and Mehta NN
- Subjects
- Adult, Cohort Studies, Coronary Artery Disease blood, Female, Humans, Longitudinal Studies, Male, Middle Aged, Psoriasis pathology, Severity of Illness Index, Time Factors, Computed Tomography Angiography, Coronary Artery Disease diagnostic imaging, Psoriasis complications, Scavenger Receptors, Class E blood
- Abstract
Importance: Psoriasis, a chronic inflammatory skin disease associated with accelerated noncalcified coronary burden (NCB) by coronary computed tomography angiography (CCTA), accelerates lipoprotein oxidation in the form of oxidized modified lipoproteins. A transmembrane scavenger receptor for these oxidized modified lipoproteins is lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1), which has been reported to be associated with coronary artery disease. It is unknown whether this receptor is associated with coronary artery disease in psoriasis., Objective: To assess the association between soluble LOX-1 (sLOX-1) and NCB in psoriasis over time., Design, Setting, and Participants: In a cohort study at the National Institutes of Health, 175 consecutive patients with psoriasis were referred from outpatient dermatology practices between January 1, 2013, and October 1, 2017. A total of 138 consecutively recruited patients with psoriasis were followed up at 1 year., Exposures: Circulating soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were measured blindly by field scientists running undiluted serum using an enzyme-linked immunosorbent assay., Main Outcomes and Measures: Coronary computed tomography angiography scans were performed to quantify NCB in all 3 major epicardial coronary arteries by a reader blinded to patient demographics, visit, and treatment status., Results: Among the 175 patients with psoriasis, the mean (SD) age was 49.7 (12.6) years and 91 were men (55%). The cohort had relatively low median cardiovascular risk by Framingham risk score (median, 2.0 [interquartile range (IQR), 1.0-6.0]) and had a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) suggestive of overweight profiles (29.6 [6.0]). Elevated sLOX-1 levels were found in patients with psoriasis compared with age- and sex-matched controls (median, 210.3 [IQR, 110.9-336.2] vs 83.7 [IQR, 40.1-151.0]; P < .001), and were associated with Psoriasis Area Severity Index (PASI) score (β = 0.23; 95% CI, 0.082-0.374; P = .003). Moreover, sLOX-1 was associated with NCB independent of hyperlipidemia status (β = 0.11; 95% CI, 0.016-0.200; P = .023), an association which persisted after adjusting for traditional cardiovascular risk factors, statin use, and biologic psoriasis treatment (β = 0.10; 95% CI, 0.014-0.193; P = .03). At 1 year, in those who had clinical improvement in PASI (eg, >50% improvement), a reduction in sLOX-1 (median, 311.1 [IQR, 160.0-648.8] vs median, 224.2 [IQR, 149.1 - 427.4]; P = .01) was associated with a reduction in NCB (β = 0.14; 95% CI, 0.028-0.246; P = .02)., Conclusions and Relevance: Soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were elevated in patients with psoriasis and were associated with severity of skin disease. Moreover, sLOX-1 associated with NCB independent of hyperlipidemia status, suggesting that inflammatory sLOX-1 induction may modulate lipid-rich NCB in psoriasis. Improvement of skin disease was associated with a reduction of sLOX-1 at 1 year, demonstrating the potential role of sLOX-1 in inflammatory atherogenesis in psoriasis.
- Published
- 2020
- Full Text
- View/download PDF
5. Cardiomyocyte-myofibroblast contact dynamism is modulated by connexin-43.
- Author
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Schultz F, Swiatlowska P, Alvarez-Laviada A, Sanchez-Alonso JL, Song Q, de Vries AAF, Pijnappels DA, Ongstad E, Braga VMM, Entcheva E, Gourdie RG, Miragoli M, and Gorelik J
- Subjects
- Animals, Antineoplastic Agents pharmacology, Cells, Cultured, Gap Junctions, Male, Myocytes, Cardiac cytology, Myocytes, Cardiac drug effects, Myofibroblasts cytology, Myofibroblasts drug effects, Phenylbutyrates pharmacology, Rats, Rats, Sprague-Dawley, Cell Adhesion, Cell Communication, Cell Movement, Connexin 43 metabolism, Myocytes, Cardiac physiology, Myofibroblasts physiology
- Abstract
Healthy cardiomyocytes are electrically coupled at the intercalated discs by gap junctions. In infarcted hearts, adverse gap-junctional remodeling occurs in the border zone, where cardiomyocytes are chemically and electrically influenced by myofibroblasts. The physical movement of these contacts remains unquantified. Using scanning ion conductance microscopy, we show that intercellular contacts between cardiomyocytes and myofibroblasts are highly dynamic, mainly owing to the edge dynamics (lamellipodia) of the myofibroblasts. Decreasing the amount of functional connexin-43 (Cx43) at the membrane through Cx43 silencing, suppression of Cx43 trafficking, or hypoxia-induced Cx43 internalization attenuates heterocellular contact dynamism. However, we found decreased dynamism and stabilized membrane contacts when cellular coupling was strengthened using 4-phenylbutyrate (4PB). Fluorescent-dye transfer between cells showed that the extent of functional coupling between the 2 cell types correlated with contact dynamism. Intercellular calcein transfer from myofibroblasts to cardiomyocytes is reduced after myofibroblast-specific Cx43 down-regulation. Conversely, 4PB-treated myofibroblasts increased their functional coupling to cardiomyocytes. Consistent with lamellipodia-mediated contacts, latrunculin-B decreases dynamism, lowers physical communication between heterocellular pairs, and reduces Cx43 intensity in contact regions. Our data show that heterocellular cardiomyocyte-myofibroblast contacts exhibit high dynamism. Therefore, Cx43 is a potential target for prevention of aberrant cardiomyocyte coupling and myofibroblast proliferation in the infarct border zone.-Schultz, F., Swiatlowska, P., Alvarez-Laviada, A., Sanchez-Alonso, J. L., Song, Q., de Vries, A. A. F., Pijnappels, D. A., Ongstad, E., Braga, V. M. M., Entcheva, E., Gourdie, R. G., Miragoli, M., Gorelik, J. Cardiomyocyte-myofibroblast contact dynamism is modulated by connexin-43.
- Published
- 2019
- Full Text
- View/download PDF
6. Fibroblast-myocyte coupling in the heart: Potential relevance for therapeutic interventions.
- Author
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Ongstad E and Kohl P
- Subjects
- Animals, Cardiotonic Agents therapeutic use, Cell Communication drug effects, Cicatrix genetics, Cicatrix pathology, Cicatrix prevention & control, Connexins genetics, Fibroblasts drug effects, Fibroblasts pathology, Fibrosis genetics, Fibrosis pathology, Fibrosis therapy, Gap Junctions drug effects, Gene Expression Regulation, Heart Conduction System drug effects, Humans, Membrane Potentials drug effects, Myocardium metabolism, Myocardium pathology, Myocytes, Cardiac drug effects, Myocytes, Cardiac pathology, Signal Transduction, Cicatrix metabolism, Connexins metabolism, Fibroblasts metabolism, Fibrosis metabolism, Myocytes, Cardiac metabolism
- Abstract
Cardiac myocyte-fibroblast electrotonic coupling is a well-established fact in vitro. Indirect evidence of its presence in vivo exists, but few functional studies have been published. This review describes the current knowledge of fibroblast-myocyte electrical signaling in the heart. Further research is needed to understand the frequency and extent of heterocellular interactions in vivo in order to gain a better understanding of their relevance in healthy and diseased myocardium. It is hoped that associated insight into myocyte-fibroblast coupling in the heart may lead to the discovery of novel therapeutic targets and the development of agents for improving outcomes of myocardial scarring and fibrosis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
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