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- Holmes, Michael V., et al.
(author)
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Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
- 2013
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In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
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Journal article (peer-reviewed)abstract
- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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| 2. |
- Frisk, U., et al.
(author)
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The Odin satellite - I. Radiometer design and test
- 2003
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 402:3, s. L27-L34
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Journal article (peer-reviewed)abstract
- The Sub-millimetre and Millimetre Radiometer (SMR) is the main instrument on the Swedish, Canadian, Finnish and French spacecraft Odin. It consists of a 1.1 metre diameter telescope with four tuneable heterodyne receivers covering the ranges 486-504 GHz and 541-581 GHz, and one fixed at 118.75 GHz together with backends that provide spectral resolution from 150 kHz to 1 MHz. This Letter describes the Odin radiometer, its operation and performance with the data processing and calibration described in Paper II.
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| 3. |
- Mohanta, S. K., et al.
(author)
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Neuroimmune cardiovascular interfaces control atherosclerosis
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 605, s. 152-159
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Journal article (peer-reviewed)abstract
- Atherosclerotic plaques develop in the inner intimal layer of arteries and can cause heart attacks and strokes(1). As plaques lack innervation, the effects of neuronal control on atherosclerosis remain unclear. However, the immune system respondsto plaques by forming leukocyte infiltrates in the outer connective tissue coat of arteries (the adventitia)(2-6). Here, because the peripheral nervous system uses the adventitia as its principal conduit to reach distant targets(7-9), we postulated that the peripheral nervous system may directly interact with diseased arteries. Unexpectedly, widespread neuroimmune cardiovascular interfaces (NICIs) arose in mouse and human atherosclerosis-diseased adventitia segments showed expanded axon networks, includinggrowth cones at axon endings near immune cells and media smooth muscle cells. Mouse NICIs established a structural artery-brain circuit (ABC): abdominal adventitia nociceptive afferents(10-14) entered the central nervous system through spinal cord T-6-T-13 dorsal root ganglia and were traced to higher brain regions, including the parabrachial and central amygdala neurons; and sympathetic efferent neurons projected from medullary and hypothalamic neuronsto the adventitia through spinal intermediolateral neurons and both coeliac and sympathetic chain ganglia. Moreover, ABC peripheral nervous system components were activated: splenic sympathetic and coeliac vagus nerve activities increased in parallel to disease progression, whereas coeliacganglionectomy led to the disintegration of adventitial NICIs, reduced disease progression and enhanced plaque stability. Thus, the peripheral nervous system uses NICIs to assemble a structural ABC, and therapeutic intervention in the ABC attenuates atherosclerosis.
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| 4. |
- Tsiantoulas, D., et al.
(author)
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APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 597, s. 92-96
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Journal article (peer-reviewed)abstract
- Atherosclerotic cardiovascular disease causes heart attacks and strokes, which are the leading causes of mortality worldwide(1). The formation of atherosclerotic plaques is initiated when low-density lipoproteins bind to heparan-sulfate proteoglycans (HSPGs)(2) and become trapped in the subendothelial space of large and medium size arteries, which leads to chronic inflammation and remodelling of the artery wall(2). A proliferation-inducing ligand (APRIL) is a cytokine that binds to HSPGs(3), but the physiology of this interaction is largely unknown. Here we show that genetic ablation or antibody-mediated depletion of APRIL aggravates atherosclerosis in mice. Mechanistically, we demonstrate that APRIL confers atheroprotection by binding to heparan sulfate chains of heparan-sulfate proteoglycan 2 (HSPG2), which limits the retention of low-density lipoproteins, accumulation of macrophages and formation of necrotic cores. Indeed, antibody-mediated depletion of APRIL in mice expressing heparan sulfate-deficient HSPG2 had no effect on the development of atherosclerosis. Treatment with a specific anti-APRIL antibody that promotes the binding of APRIL to HSPGs reduced experimental atherosclerosis. Furthermore, the serum levels of a form of human APRIL protein that binds to HSPGs, which we termed non-canonical APRIL (nc-APRIL), are associated independently of traditional risk factors with long-term cardiovascular mortality in patients with atherosclerosis. Our data reveal properties of APRIL that have broad pathophysiological implications for vascular homeostasis.
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| 9. |
- Khanal, S, et al.
(author)
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Thermal Characterization of THz Schottky Diodes Using Transient Current Measurements
- 2014
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In: IEEE Transactions on Terahertz Science and Technology. - 2156-342X .- 2156-3446. ; 4:2, s. 267-276
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Journal article (peer-reviewed)abstract
- This paper presents a new method for thermal characterization of THz Schottky diodes. The method is based on the transient current behavior, and it enables the extraction of thermal resistances, thermal time-constants, and peak junction temperatures of THz Schottky diodes. Many typical challenges in thermal characterization of small-area diode devices, particularly those related to self-heating and electrical transients, are either avoided or mitigated. The method is validated with measurements of commercially available single-anode Schottky varactor diodes. A verification routine is performed to ensure the accuracy of the measurement setup, and the characterization results are compared against an in-house measurement-based method and against simulation results of two commercial 3-D thermal simulators. For example, characterization result for the total thermal resistance of a Schottky diode with an anode area of 9 $muhbox{m}^{2}$ is within 10% of the average value of 4020 K/W when using all four approaches. The new method can be used to measure small diode devices with thermal time constants down to about 300 ns with the measurement setup described in the paper.
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