Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells

Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20-50 \u3bcg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 \ub1 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 \ub1 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 \u3bcg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 \u3bcg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL

HAS-1 genetic polymorphism in sporadic abdominal aortic aneurysm

The hyaluronan synthase 1 (HAS-1) gene encodes a plasma membrane protein that synthesizes hyaluronan (HA), an extracellular matrix molecule. Accumulating evidence emphasizes the relevance of HA metabolism in an increasing number of processes of clinical interest, including abdominal aortic aneurysm (AAA). The existence of aberrant splicing variants of the HAS-1 gene could partly explain the altered extracellular matrix architecture and influence various biological functions, resulting in progressive arterial wall failure in the development of AAA. In the present study, we assessed the hypothesis that HAS-1 genetic 833A/G polymorphism could be associated with the risk of AAA by performing a case-control association study, involving AAA patients and healthy matched donors

Versican is differentially regulated in the adventitial and medial layers of human vein grafts.

Changes in extracellular matrix proteins may contribute significantly to the adaptation of vein grafts to the arterial circulation. We examined the production and distribution of versican and hyaluronan in intact human vein rings cultured ex vivo, veins perfused ex vivo, and cultured venous adventitial and smooth muscle cells. Immunohistochemistry revealed higher levels of versican in the intima/media compared to the adventitia, and no differences in hyaluronan. In the vasa vasorum, versican and hyaluronan associated with CD34+ progenitor cells. Culturing the vein rings for 14 days revealed increased versican immunostaining of 30-40% in all layers, with no changes in hyaluronan. Changes in versican accumulation appear to result from increased synthesis in the intima/media and decreased degradation in the adventitia as versican transcripts were increased in the intima/media, but unchanged in the adventitia, and versikine (the ADAMTS-mediated cleavage product of versican) was increased in the intima/media, but decreased in the adventitia. In perfused human veins, versican was specifically increased in the intima/media in the presence of venous pressure, but not with arterial pressure. Unexpectedly, cultured adventitial cells express and accumulate more versican and hyaluronan than smooth muscle cells. These data demonstrate a differential regulation of versican and hyaluronan in human venous adventitia vs. intima/media and suggest distinct functions for these extracellular matrix macromolecules in these venous wall compartments during the adaptive response of vein grafts to the arterial circulation

Extraction of a model for a microwave Power pHEMT

This article presents the development of a large-signal transistor model for a power microwave pseudomorphic high-electron mobility transistor (pHEMT). This model won the first prize in the Microwave Transistor Modeling student competition held during the 2013 IEEE Microwave Theory and Techniques Society (MTT-S) International Microwave Symposium (IMS2013) in Seattle, Washington

Broadband high-power GaN SPDT switch using stacked-shunt fets and resonance inductors

This article presents a new GaN HEMT-based high-power single-pole double-throw (SPDT) switch operating over the X-band frequencies. The GaN SPDT MMIC switch is presented, having good return loss (better than 16.8 dB) and insertion loss (1.4 dB) measured across X-band. It also has a very high power-handling capability, with a measured 1 dB compression point of 38 dBm. The techniques and design principles leading to this level of performance are discussed. Circuit performance is confirmed by experimental and simulation results, which are in good agreement up to 20 GHz

High-power X-band GaN switched-filter phase shifter

This paper presents a high-power switched-filter GaN phase shifter, designed for X-band and offering good performance from 8-16 GHz. The manufactured 0°/22.5° switched-filter phase shifter has much wider bandwidth than is typically found with this configuration, while maintaining low insertion loss ( 11.15 dB) and an amplitude imbalance of less than 1.03 dB across X-band. The 1 dB compression point was higher than laboratory equipment was able to measure (> 38 dBm) and the phase shifter MMIC exhibited an IIP3 higher than 46 dBm. The proposed high-power phase shifter has been fabricated in a 0.5 μm GaN HEMT process and was designed using an accurate, customized switch FET model

A new type of Robust broadband GaN HEMT-based high power high-pass/low-pass 22.5 phase shifter

This article proposes a new type of GaN HEMT-based high power phase shifter operating at X-band. The design includes a 22.5 phase shift network and a high power SPDT switch. The design and resulting performance are discussed in detail and are confirmed by experimental and simulation results, which are in good agreement up to 20 GHz. The one bit phase shifter exhibits good phase performance, insertion loss, and return loss. The proposed phase shifter MMIC has been successfully demonstrated using a 0.5 μm gate GaN HEMT process