LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis.

BACKGROUND: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1, has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis. METHODS: We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice (Apoe-/-PSMB8-AS1KI) and global Apoe and proteasome subunit-ß type-9 (Psmb9) double knockout mice (Apoe-/-Psmb9-/-). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks. RESULTS: Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe-/-PSMB8-AS1KI mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe-/- mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe-/-PSMB8-AS1KI mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that PSMB8-AS1 induced PSMB9 transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the PSMB9 promoter. PSMB9 (proteasome subunit-ß type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1). Psmb9 deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in Apoe-/- mice in vivo. Importantly, endothelial overexpression of PSMB8-AS1-increased atherosclerosis and vascular inflammation were attenuated by Psmb9 knockout. CONCLUSIONS: PSMB8-AS1 promotes vascular inflammation and atherosclerosis via the NONO/PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA-based strategies to counteract atherosclerotic cardiovascular disease.

A novel role for YPEL2 in mediating endothelial cellular senescence via the p53/p21 pathway.

Yippee-like 2 (YPEL2) is expressed in tissues and organs enriched in vascular networks, such as heart, kidney, and lung. However, the roles of YPEL2 in endothelial cell senescence and the expression of YPEL2 in atherosclerotic plaques have not yet been investigated. Here, we report the essential role of YPEL2 in promoting senescence in human umbilical vein endothelial cells (HUVECs) and the upregulation of YPEL2 in human atherosclerotic plaques. YPEL2 was significantly upregulated in both H2O2-induced senescent HUVECs and the arteries of aged mice. Endothelial YPEL2 deficiency significantly decreased H2O2-increased senescence-associated beta-galactosidase (SA-ß-gal) activity and reversed H2O2-inhibited cell viability. Additionally, endothelial YPEL2 knockdown reduced H2O2-promoted THP-1 cell adhesion to HUVECs and downregulated ICAM1 and VCAM1 expression. Mechanistic studies divulged that the p53/p21 pathway was involved in YPEL2-induced cellular senescence. We conclude that YPEL2 promotes cellular senescence via the p53/p21 pathway and that YPEL2 expression is elevated in atherosclerosis. These findings reveal YPEL2 as a potential therapeutic target in aging-associated diseases.

EPSTI1 promotes monocyte adhesion to endothelial cells in vitro via upregulating VCAM-1 and ICAM-1 expression.

Atherosclerosis is a chronic inflammatory disease of arterial wall, and circulating monocyte adhesion to endothelial cells is a crucial step in the pathogenesis of atherosclerosis. Epithelial-stromal interaction 1 (EPSTI1) is a novel gene, which is dramatically induced by epithelial-stromal interaction in human breast cancer. EPSTI1 expression is not only restricted to the breast but also in other normal tissues. In this study we investigated the role of EPSTI1 in monocyte-endothelial cell adhesion and its expression pattern in atherosclerotic plaques. We showed that EPSTI1 was dramatically upregulated in human and mouse atherosclerotic plaques when compared with normal arteries. In addition, the expression of EPSTI1 in endothelial cells of human and mouse atherosclerotic plaques is significantly higher than that of the normal arteries. Furthermore, we demonstrated that EPSTI1 promoted human monocytic THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs) via upregulating VCAM-1 and ICAM-1 expression in HUVECs. Treatment with LPS (100, 500, 1000 ng/mL) induced EPSTI1 expression in HUVECs at both mRNA and protein levels in a dose- and time-dependent manner. Knockdown of EPSTI1 significantly inhibited LPS-induced monocyte-endothelial cell adhesion via downregulation of VCAM-1 and ICAM-1. Moreover, we revealed that LPS induced EPSTI1 expression through p65 nuclear translocation. Thus, we conclude that EPSTI1 promotes THP-1 cell adhesion to endothelial cells by upregulating VCAM-1 and ICAM-1 expression, implying its potential role in the development of atherosclerosis.

The zonal pattern of arterial supply to the brachial plexus and its clinical significance.

PURPOSE: To provide the anatomical basis of blood supply of brachial plexus for the clinical microsurgical treatment of brachial plexus injury. METHODS: Thirteen adult anticorrosive cadaveric specimens (8 males, 5 females) were dissected in this study. 3 fresh cases (2 males, 1 female) were used to observe the zonal pattern of arteries supplying brachial plexus, and 10 cases (6 males, 4 females) were used to observe the source and distribution of the brachial plexus arteries under microscope. RESULTS: The brachial plexus is supplied by branches of the subclavian-axillary axis (SAA), and these branches anastomose each other. According to distribution feature, blood supply of the brachial plexus could be divided into three zones. The first zone was from the nerve roots of intervertebral foramina to its proximal trunks, which was supplied by the vertebral artery and the deep cervical artery. The second zone was from the distal nerve trunks of the brachial plexus, encompassing the divisions to its proximal cords, which was supplied by direct branches of the subclavian artery or by branches originating from the dorsal scapular artery. The third zone was from the distal portion of the cords to terminal branches of the brachial plexus, which was supplied by direct branches of the axillary artery. CONCLUSIONS: The zonal pattern of arterial supply to the brachial plexus is a systematic and comprehensive modality to improve anatomical basis for the clinical microsurgical treatment for brachial plexus injury.

Effects of Cd(II) on wastewater biological nitrogen and phosphorus removal.

Short-term and long-term effects of Cd(II) on wastewater biological nitrogen and phosphorus removal were investigated with respect to microorganism abundances, enzyme activities, and polyhydroxyalkanoates (PHAs) and glycogen transformations. Though no obvious effects on wastewater biological nutrient removal were observed after short-term exposure, the long-term exposure of 10 mg L(-)(1) Cd(II) inhibited nitrification and phosphorus uptake. Compared with the absence of Cd(II), the presence of 10 mg L(-1) of Cd(II) decreased total nitrogen and phosphorus removal efficiencies from 97% and 98% to 88% and 18%, respectively. Mechanism studies revealed that Cd(II) affected the transformations of intracellular PHAs and glycogen, and the activities of oxidoreductase and polyphosphate kinase, resulted in the decrease of nitrite oxidizing bacteria and polyphosphate accumulating organisms abundance, which might be the major reason for the negative effects of long-term exposure to 10 mg L(-1) Cd(II) on biological nitrogen and phosphorus removal.

Three-dimensional visualization of the cutaneous angiosome using angiography.

The purpose of this study was to establish the three-dimensional (3D) architecture of the cutaneous angiosome for assessment and design of the perforator flaps. Two fresh cadavers were injected with carboxymethyl cellulose (CMC)/lead oxide and computed tomography (CT) scanned before and after the injection. The various parts of the cutaneous and subcutaneous tissue derived from one of the injected cadavers were also CT scanned. Three-dimensional reconstruction of the cutaneous angiosome and the two flap designs were performed using Materialise's Interactive Medical Image Control System (MIMICS). Both the reconstructed cutaneous angiosomes and the digital flaps can be displayed independently or in conjunction with bones, source arteries, and skin. The 3D architecture of the cutaneous angiosome ensures clear display of the spatial location, distribution range, and anastomoses relationship of the cutaneous perforators. In addition, the caliber, length, and position of a particular source artery are illustrated in the exact spatial location. As a result, the technique provides visualization of the general area and the expandable direction of a respective flap. This technique has the potential to play an important role in assessing perforator blood supply territory and in the design of new flaps.

[Clinical application of the free superficial peroneal artery perforator flap].

OBJECTIVE: To investigate the applied anatomy of the superficial peroneal artery perforator flap and report the clinical results of repairing the soft tissue defects with free perforator flaps. METHODS: 15 fresh cadavers were injected with a modified lead oxide-gelatin mixture for three-dimensional visualization reconstruction using a 16-slice spiral computed tomography scanner and specialized software (Materiaise's interactive medical image control system, MIMICS). The origin, course and distribution of the superficial peroneal artery perforator in the anterolateral leg region were observed. Clinically 6 cases with hand defects and 6 cases with feet defects were treated with free superficial peroneal artery perforator flap transplantation. The defect size ranged from 3.0 cm x 4.5 cm to 5.0 cm x 11.0 cm. RESULTS: The diameter of the superficial peroneal artery is (1.2 +/- 0.3) mm at its origin from the anterior tibial artery 5 cm below the fibula head. It is (5.6 +/- 1.8) cm in length. This artery is truly anastomosed with other perforators to form the chain of superficial peroneal nerve accessory artery. The superficial peroneal artery perforators [outer diameter (0.7 +/- 0.2) mm] with a vein are in the anterolateral leg region, supplying the skin in proximal-middle region. All the 12 cases were treated successfully. The clinical results were satisfactory after 3-12 months of following-up. CONCLUSIONS: The superficial peroneal artery perforator flap has constantly, reliable blood supply, and good texture. It is a good option for repairing soft-tissue defect with free transfer.

Measurement and analysis of the perforator arteries in upper extremity for the flap design.

The aim of this study was to provide the anatomical basis for the skin flap pedicled with the nutrient vessels of the cutaneous nerves and cutaneous veins of the upper extremity. Radio-opaque material was injected into the common carotid arteries of five fresh cadavers. The skin and the fascia were meticulously dissected, removed, and radiographed. The Photoshop CS and Scion image 4.02 were used to analyze the cutaneous arteries, the density of vessels, and the vascular territories of the perforator arteries. The results showed that the cutaneous arteries of the upper extremity came from 16 original arteries, and accordingly, the superficial tissue of the upper extremity could be divided into 16 vascular territories. The external diameter and the area of blood supply of each perforator were growing downwards from the proximum to the distal end. But the points at which the perforator arteries came out from the deep tissue were concentrated near the cutaneous nerves and cutaneous veins, and the arteries formed vascular chains. The density of the arteries near the cutaneous nerves and cutaneous veins was much higher than that of other areas. This article discussed the regularity of the nutrient vessels of the cutaneous nerves and veins on the basis of the experimental results.

Demonstration of three injection methods for the analysis of extrinsic and intrinsic blood supply of the peripheral nerve.

BACKGROUND: The use of free vascularized nerve grafts requires an intimate and accurate knowledge of the blood supply of peripheral nerve. This study was designed to compare the advantages and disadvantages of three methods employed to reveal the blood supply of the peripheral nerve, and to provide morphological basis for vascularized nerve grafts. METHODS: The blood supply of brachial plexus and its main branches (ulnar, median, radial, musculocutaneous and axillary nerve) were observed using three vascular injection techniques: three specimens were injected with red latex through the thoracic aorta; two side specimens were injected with a Chinese ink solution, through the subclavian artery, for diaphanization and histology; one fresh cadaver was injected with the gelatin-lead oxide mixture through the femoral artery for radiography. RESULTS: The blood supply of the brachial plexus and its main branches was well examined using the three different vascular injection techniques. Perfusion with red latex exposed the extrinsic blood supply. Diaphanization and histology showed the intrinsic blood supply, while gelatin-lead oxide injection technique interactively displayed both the intrinsic and extrinsic blood supply to the peripheral nerve. CONCLUSION: The standard method for the study of the extrinsic blood supply to the peripheral nerve is the red latex perfusion; diaphanization and histology are very suitable to study the intrinsic blood supply of the peripheral nerve; while gelatin-lead oxide technique is the standard for visualization of the integral topography of the blood supply of the peripheral nerve.

Three-dimensional visualization of pelvic vascularity.

The aim of this study was to establish a 3D digitized model of pelvic vasculature for anatomic study, preoperative planning, and virtual reality. Three adult fresh cadavers were perfused with carboxymethyl cellulose/lead oxide mixture to mark blood vessels, and subjected to multilayer spiral computed tomography scanning to obtain a series of thin sections. Then, the 2D images of the pelvis and pelvic blood vessels were transformed into 3D digitized models using Mimics 11.0. The 2D images of carboxymethyl cellulose/lead oxide filled arteries had the features of entire outline and few constructed defects. The 3D digitized models of the pelvis and pelvic artery system displayed spatial location and the adjacent relationship of arteries with the pelvis. Not only the well-known arteries but also the tiny blood vessels in the reconstructed structures were well demonstrated and observed interactively. The reconstructed tissue flaps, including a lobulated skin flap with the pedicle of superficial epigastric artery, and an iliac flap with the pedicle of deep iliac circumflex artery, demonstrated their blood supply area. This indicated that the modified technique of vascular perfusion with carboxymethyl cellulose/lead oxide and reconstitution with Mimics 11.0 software contributed to 3D digitized model of pelvic vasculature.

Three-dimensional reconstructive methods in the visualization of anterolateral thigh flap.

INTRODUCTION: Developments in the field of digitalized technique and three-dimensional (3D) reconstruction methods allowed a precise description of anatomy structures. With the development of computer reconstructive techniques, we could get more precise anatomic images. Digitized visible models of these structures can be as a useful tool in clinical training. The purpose of this study was to observe the anatomy of arteria circumflexa femoris lateralis (ACFL) flap and to discuss the methods in the visualization of anterolateral thigh (ATL) flap by digitalized technique. METHODS: Six adults volunteer underwent contrast-enhanced CT angiography of pelvic and lower limbs utilizing a 64-row multi-slice spiral CT after median cubital vein injection with Ultravist (3.5 ml/s). 2D images from these data in Dicom format were transformed into computer. Next two adult fresh cadaver specimens, one male and one female, were subject to radiographic CT scanning before and after perfused with lead oxide-gelatine mixture, whose collimation are 0.5 mm (120 kV, 110 mA, 512 x 512 matrix). Through Amira 3.1 (TGS) software, the 2D images in Dicom format were transformed into the 3D models of the entire region. The structures of arteria circumflexa femoris lateralis (ACFL) were observed and the digitized visible models of ALT flap were established through 3D computerized reconstructions methods from these data using Amira 3.1 software. Then merging volume rendering with surface rendered reconstruction from lead oxide-gelatine mixture perfusion database. RESULTS: The 3D reconstructed visible models established from these datasets perfectly displayed the characteristic of ACFL and ALT flap anatomy. CONCLUSION: The digitized models could offer the anatomy of ALT flap perfectly, and the reconstructed methods may be used in other flap reconstruction with 3D demonstration.

[Anatomic study of peroneal tendofascial flap combined with adipofascial flap for the repair of heel tissue defects].

OBJECTIVE: To study the anatomy of peroneal tendofascial flap combined with adipofascial flap for the repair of heel tissue defects. METHODS: The lower extremities of five cadavers (10 sides) were perfused with red latex, the blood supply of peroneal tendofascial flap and vicinity adipofascial flap were observed. The diameter, course, branches and location of the blood vessels were measured. Eight fresh cadavers (16 sides) were perfused with lead oxide-gelatine mixture. The covering fascia tissues of the lower extremities was obtained and photographed by X-ray. The vascular anastomosis and association of nutrient vessel of peroneal tendofascial flap and vicinity adipofascial flap were observed. Two adult lower extremities specimens (4 sides) were used to construct vessel diagrams for observation of the course, distribution and anastomosis of the vessels. Eight cases were treated successfully with theses flaps. RESULTS: The blood supply of the combined fascial flap is multi-originated. For the area within 4 cm below and above the lateral malleolus cusp, the blood supply includes 2-5 branches from heel lateral artery with an average diameter of (0.5 +/- 0.2) mm, 1-2 branches from posterior lateral malleolus artery with an average diameter of (0.6 +/- 0.2) mm and 2-3 branches from the descending part of perforating branches of peroneal artery with an average diameter of (0.5 +/- 0.2) mm. The blood supply of area 4 cm above lateral malleolus cusp is 1-3 branches from intermuscular septum perforating branches of peroneal artery with an average diameter of (1.0 +/- 0.2) mm. These above branches are anastomosed each other and also send off many smaller branches to form vascular net around tendon. The fascial flaps and free skin grafts in eight patients were completely survived. All patients were followed up for 3-24 months, the donor and recipient sites were healed very well. The functional and cosmetic results were satisfactory. CONCLUSIONS: Peroneal tendofascial flap combined with adipofascial flap, with proximal pedicle or reverse distal pedicle, can be used to repair the defect at the lower leg and refractory small- and medium-sized defects at the heel.

Application of three-dimensional digitalized reconstruction of an anterolateral thigh flap and an arterial dorsalis pedis flap.

Developments in the field of digitalized technique and three-dimensional (3D) reconstruction methods allowed a precise description of anatomy structures. With the development of Visible Human Project (1989) and Virtual Chinese Human (VCH) techniques, we could get more precise anatomic images. Digitized visible models of these structures can be a useful tool in clinical training. Combining modern radiology and VCH techniques, we designed a method to establish digitized visible models of anterolateral thigh (ALT) flap and arteria dorsalis pedis (ADP) flap from adult fresh cadaver specimens perfused with lead oxide-gelatine mixture and VCH Male III dataset. The 3D reconstructed visible models established from these datasets perfectly displayed the anatomic structures of ALT flap and ADP flap. This is the first report on the ACFL and ADP structures which were reconstructed digitally.

[Study on vascular morphology of integument tissues of the channel area in the leg].

OBJECTIVE: To observe the distribution of the blood vessels in the integument tissue of the channel area of legs. METHODS: The integument tissue of the lower limbs in the 12 cadavers were dissected with macro-and micro-dissection, radiographical technique of systemic artery and technique of image pattern analysis to observe and analyze the origins, branches and anastomoses in the integument tissues along the channels of legs. RESULTS: The distributional density of the blood vessels in the integument tissues of legs along the channel area of the three-yin meridians of the foot, the Gallbladder Meridian, and the Urinary Bladder Meridian was higher than that in the other parts. They formed an obvious nutrient vascular chain on the arteriogram. The distributional density in the channel area of the Stomach Meridian was not obviously increased and the obvious nutrient vascular chain could not be seen. CONCLUSION: An obvious nutrient vascular chain is formed in the integument tissue along the channel area of legs except the Stomach Meridian.