The performance of cross-linked acellular arterial scaffolds as vascular grafts; pre-clinical testing in direct and isolation loop circulatory models

There is a significant need for small diameter vascular grafts to be used in peripheral vascular surgery; however autologous grafts are not always available, synthetic grafts perform poorly and allografts and xenografts degenerate, dilate and calcify after implantation. We hypothesized that chemical stabilization of acellular xenogenic arteries would generate off-the-shelf grafts resistant to thrombosis, dilatation and calcification. To test this hypothesis, we decellularized porcine renal arteries, stabilized elastin with penta-galloyl glucose and collagen with carbodiimide/activated heparin and implanted them as transposition grafts in the abdominal aorta of rats as direct implants and separately as indirect, isolation-loop implants. All implants resulted in high patency and animal survival rates, ubiquitous encapsulation within a vascularized collagenous capsule, and exhibited lack of lumen thrombogenicity and no graft wall calcification. Peri-anastomotic neo-intimal tissue overgrowth was a normal occurrence in direct implants; however this reaction was circumvented in indirect implants. Notably, implantation of non-treated control scaffolds exhibited marked graft dilatation and elastin degeneration; however PGG significantly reduced elastin degradation and prevented aneurismal dilatation of vascular grafts. Overall these results point to the outstanding potential of crosslinked arterial scaffolds as small diameter vascular grafts.     

高脂血清及其脂蛋白对动脉壁胶原及弹性蛋白合成的影响

高脂血清可明显地刺激在体外温育的兔胸主动脉壁合成胶原及弹性蛋白,透析的血清仍有作用;但血清在60℃保温1小时后刺激作用明显减弱,此时血清低密度脂蛋白(LDL)的电泳行为和载脂蛋白B(ApoB)的免疫学性质也发生改变。分离的LDL 也可使胶原及弹性蛋白合成增多;高密度脂蛋白(HDL)则有降低高脂血清刺激胶原及弹性蛋白合成的效应。     

Tropoelastin gene expression in the developing vascular system of the chicken: an in situ hybridization study

Temporal and spatial patterns in the accumulation of Tropoelastin (TE) mRNA during development of the chick embryo were established by in situ hybridization. Radiolabeled oligonucleotide probes of high specific activity were hybridized to serial sections of the cardiovascular system from embryonic day 3.5 (ED 3.5) to ED 19. Tropoelastin mRNA was observed as early as ED 3.5 in the dorsal part of the arterial trunk. During septation varying levels of TE mRNA were seen in the pulmonary trunk, the aorta and the aorticopulmonary septum. Thereafter TE mRNA levels increased up to ED 12, and the appearance of message was distributed distally in the walls of developing arteries. From ED 4.5 on, we found a decreasing proximo-distal gradient of the hybridization signal along the trunks and later along the main arteries (longitudinal gradient), and a radial gradient through the arterial vessel wall with the highest levels of TE mRNA in the outer layers of the media. Both gradients persisted in all major arterial vessels except in the proximal systemic and pulmonary trunks, where the original radial gradient was inverted or locally bimodal during the second half of development. The valvular region of aortic and pulmonary trunks showed particularly striking patterns of TE mRNA distribution, notably a prominent label on the endothelial cell layer on aortic and pulmonary valves. Outside the cardiovascular system, TE mRNA was mainly present in prochondral or perichondral cells in trachea and growing skeleton, and in the gap of growing joints. In kidney or nephric primordia, TE mRNA was only detectable in the wall of renal arteries. A hybridization signal was observed on mesenchyme of pulmonary septae at ED 16. Our results suggest a complex regulation of elastin gene expression during development, particularly within the proximal regions of the large arterial vessels.     

Alpha-1-antitrypsin and the pathogenesis of emphysema

The review examines the relationship between alpha₁-antitrypsin (α ₁AT) and emphysema. Although other defects occur in subjects with alpha₁-antitrypsin deficiency, it seems likely that a reduction in inhibition due to loss of this inhibitor explains their emphysema. There is a great deal of controversy, however, concerning the role of alpha₁-antitrypsin in subjects without inherited deficiency. There is uncertainty about the presence and function of other elastase inhibitors in the peripheral lung. The function of lungα ₁AT and the presence of elastase activity are dependent upon the techniques used and this probably accounts for different results between research groups. In addition, other relevant factors such as which enzymes cause lung elastolysis, control of neutrophil chemotaxis, and mechanisms of elastin synthesis and repair are less well studied. The overall conclusion is that many aspects of the elastase/antielastase hypothesis of emphysema are poorly understood. Without further information the true role ofα ₁AT will remain largely speculative.     

Zonular fibers, multimolecular composition as related to function (elasticity) and pathology

Zonular fibers (ZF) play an important role in accommodation. With the rapid increase over the last decade of the oldest part of the population in industrialized countries, age-dependent loss of accommodation became an increasingly important problem. It appeared therefore interesting to review old and recent literature on ZF, their composition, structure and pathological alterations. By comparing former and recent reports it appeared to us, that several previous reports were not sufficiently taken in consideration for the understanding of the rheological properties of ZF. Elastin and proteoglycans-glycosaminoglycans were reported previously as constituents of ZF. Their presence besides fibrillin, the major constituent, helps to explain the rheological properties of these fibers, and especially their elasticity and its age- and pathology-dependent decline. Our review points also to some of the major problems, which remain to be addressed by future experiments.     

Development of Tissue‐Engineered Ligaments: Elastin Promotes Regeneration of the Rabbit Medial Collateral Ligament

When ligaments are injured, reconstructive surgery is sometimes required to restore function. Methods of reconstructive surgery include transplantation of an artificial ligament and autotransplantation of a tendon. However, these methods have limitations related to the strength of the bone–ligament insertion and biocompatibility of the transplanted tissue after surgery. Therefore, it is necessary to develop new reconstruction methods and pursue the development of artificial ligaments. Elastin is a major component of elastic fibers and ligaments. However, the role of elastin in ligament regeneration has not been described. Here, we developed a rabbit model of a medial collateral ligament (MCL) rupture and treated animal knees with exogenous elastin [100 µg/(0.5 mL·week)] for 6 or 12 weeks. Elastin treatment increased gene expression and protein content of collagen and elastin (gene expression, 6‐fold and 42‐fold, respectively; protein content, 1.6‐fold and 1.9‐fold, respectively), and also increased the elastic modulus of MCL increased with elastin treatment (2‐fold) compared with the controls. Our data suggest that elastin is involved in the regeneration of damaged ligaments.     

An autopsy case of pseudoxanthoma elasticum: histochemical characteristics

An autopsy case of pseudoxanthoma elasticum is reported. A Japanese female patient complained of yellow papules on the neck, precordium, and axilla, beginning at 54 years of age. When the patient was 58 years old, in response to her visual disturbance a funduscopic examination was performed, revealing angioid streaks, and skin biopsy identified a characteristic pseudoxanthoma elasticum (PXE) lesion. The patient developed congestive heart failure, and following mitral valve prolapse and regurgitation flow into the left atrium, mitral valve replacement with a prosthetic valve was performed when the patient was 65 years old. Soon afterward, the patient complained of gait disturbance, and she died of congestive heart failure at 68 years of age. Autopsy specimen revealed fragmented, granular, and calcified elastic fibers in the middle to deep dermis and in the thickened subendocardium, and small to medium-sized muscular arteries revealed fragmented, laminated, and calcified elastic lamina; vascular changes were seen in the heart, lung, kidney, gastrointestinal tract, and iliac artery. Disrupted elastic fibers were visualized using the Weigert resorcin fuchsin method and were stained positive by antielastin and antifibronectin antibodies. Calcification was confirmed by von Kossa staining. Affected areas were PAS-positive after diastase digestion, indicating the presence of glycoprotein. Affected areas were colloidal iron-positive, indicating the presence of proteoglycan matrix.     

Fibulin-3在盆腔脏器脱垂子宫骶韧带中的表达

目的:研究Fibulin-3在子宫骶韧带组织中的表达以及与脱垂程度之间的关系。方法:应用实时定量RT-PCR和Western blot测定子宫脱垂组(POP组)46例和正常对照组28例子宫骶韧带组织中Fibulin-3 mRNA及蛋白的相对表达量。结果:两组中Fib-ulin-3均有表达,POP组骶韧带中Fibulin-3 mRNA及蛋白表达均降低,POP组Fibulin-3mRNA表达水平为0.68±0.38低于对照组的0.96±0.44(P<0.05);POP组Fibulin-3蛋白表达水平为0.76±0.48低于对照组的1.14±0.52(P<0.05),且随脱垂程度的增加表达降低(P<0.05)。结论:Fibulin-3的表达与盆腔脏器脱垂的发生相关。     

Stimulation of elastin expression by minoxidil in chick skin fibroblasts

Minoxidil inhibited the proliferation of embryonic skin fibroblasts during the growth phase but not during the stationary phase. Minoxidil stimulated elastin synthesis two-fold in a dose-dependent manner at a concentration of 1 mM during the stationary phase. The stimulation of elastin synthesis paralleled a comparable increase in elastin mRNA level. These results suggest that the stimulation of elastin expression by minoxidil in skin fibroblasts was controlled at the elastin mRNA level and also suggest that its elastinstimulating effect is not related to the suppressive effect on cell proliferation. Minoxidil appears to be a potent stimulator for elastin expression in skin fibroblasts.