Influence of Three Different Surgical Techniques on Microscopic Damage of Saphenous Vein Grafts-A Randomized Study.

Background and Objectives: The saphenous vein is one of the most common used grafts (SVG) for surgical revascularization. The mechanism of the SVGs occlusion is still unknown. Surgical preparation techniques have an important role in the early and late graft occlusion. Our study analyzed the influence of the three different surgical techniques on the histological and immunohistochemical characteristics of the vein grafts. Methods: Between June 2019 and December 2020, 83 patients who underwent surgical revascularization were prospectively randomly assigned to one of the three groups, according to saphenous vein graft harvesting (conventional (CVH), no-touch (NT) and endoscopic (EVH)) technique. The vein graft samples were sent on the histological (hematoxylin-eosin staining) and immunohistochemical (CD31, Factor VIII, Caveolin and eNOS) examinations. Results: The CVH, NT, and EVH groups included 27 patients (mean age 67.66 ± 5.6), 31 patients (mean age 66.5 ± 7.4) and 25 patients (mean age 66 ± 5.5), respectively. Hematoxylin-eosin staining revealed a lower grade of microstructural vein damage in the NT group (2, IQR 1-2) in comparison with CVH and EVH (3, IQR 2-4), (4, IQR 2-4) respectively (p < 0.001). Immunohistochemical examination revealed a high grade of staining in the NT group compared to the CVH and EVH group (CD 31 antibody p = 0.02, FVIII, p < 0.001, Caveolin, p = 0.001, and eNOS, p = 0.003). Conclusion: The best preservation of the structural vein integrity was in the NT group, while the lowest rate of leg wound complication was in the EVH group. These facts increase the interest in developing and implementing the endoscopic no-touch technique.

Morphologic comparison of blood vessels used for coronary artery bypass graft surgery.

BACKGROUND: The aim of this study was to evaluate morphologic features of healthy saphenous vein and internal thoracic artery, blood vessels used in coronary artery bypass graft (CABG) surgery, and compare results. MATERIALS AND METHODS: Ten specimens of saphenous veins and ten of internal thoracic arteries used for CABG were obtained from 20 patients. Histological routine and immunohistochemical staining was performed with: endothelin (ET), tissue inhibitor of metalloproteinase 2 (TIMP2), metallomembranoproteinase 2 (MMP2), transforming growth factor beta (TGFß), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), protein gene product 9.5 (PGP9.5), vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM). A semiquantitative evaluation method was used. RESULTS: There was found: a moderate number of endothelin-positive cells in both blood vessel types; a moderate number of MMP2-positive cells and moderate in number to numerous TIMP2-positive cells in veins. In arteries - occasionally marked positive MMP2 cells and negative TIMP2; moderate in number to numerous VEGF-positive endothelial cells on small blood vessels in vein wall and occasionally in artery wall; numerous TGFß-positive structures in veins and abundance of VCAM- and ICAM-positive cells, few in arteries; few HGF-positive structures in veins, negative in arteries; In veins, few PGP9.5-positive nerve fibres, in arteries - moderate. Moderate TUNEL reaction-positive apoptotic cells in veins and few to moderate in arteries. CONCLUSIONS: Vena saphena magna grafts are characterised by increased plasticity when it comes to modelling. Number of VEGF, VCAM and ICAM found in vena saphena magna proves the possible tendency of graft failure on basis of local blood supply intensification. Appearance of endothelin positive cells indicate the similar homeostasis condition in endotheliocytes in both - vein and artery grafts.

Transthyretin-related amyloid in a saphenous vein. Histological diagnosis in a patient undergoing coronary artery bypass surgery.

Amyloidosis is an underdiagnosed and challenging disease with clinical and etiologic heterogenicity, requiring amyloid subtyping because of the distinctive prognostic and therapeutic impact. Transthyretin amyloidosis is more common in elderly patients, and in such population undergoing cardiovascular surgery, it could be worthy to be investigated. We herein describe an unusual case of transthyretin-related vascular amyloidosis in an 81-year-old man undergoing coronary artery bypass surgery. Diagnosis done after histology showed an intimal eccentric thickening in a remnant segment of the right saphenous vein that was harvested for grafting. Transthyretin-related amyloidosis was demonstrated by histochemical Congo Red staining under polarized light and by immunohistochemistry, corresponding to the intimal thickening. The thorough histological analysis was crucial for the diagnosis of a previously unknown transthyretin-related vascular amyloidosis.

The Morphofunctional Changes in the Wall of Varicose Veins.

BACKGROUND: Varicose vein (VV) disease is a frequently occurring pathology of the lower extremities. Although the pathogenesis of varicosity development is not clearly defined, the final common pathway leading to chronic venous insufficiency is the development of venous hypertension, which is associated with severe changes in the venous wall. The aim of this study was to clarify the histological and immunohistochemical changes in great saphenous veins (GSVs) in chronic venous insufficiency. METHODS: A histopathological study was conducted on 20 patients with VVs (4 males, 16 females) and 4 (1 male, 3 females) patients undergoing distal bypass surgery. Tissues were processed for histological routine straining and immunohistochemical studies of vascular endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, protein gene product 9.5 (PGP 9.5), and collagen type IV, laminin, and fibronectin. A semiquantitative evaluation method was used. RESULTS: Compared with the normal SV, VV sections showed the damaged endothelium areas, significant disorganization of the smooth muscle bundles, and highest density of the vasa vasorum in the tunica media and tunica adventitia, as well as sclerotic blood vessels and neoangiogenesis in almost all specimens. Immunohistochemistry study showed statistically significant difference between the VVs and the control group of several parameters, such as PGP 9.5 positive structures (P < 0.05; 1-tailed significance) and laminin positive structures in subendothelial layer of VVs (P < 0.05; 1-tailed significance). There is also the tendency in increasing of VEGF expression and decreasing of collagen IV structures. Our study did not show statistically significant difference in VEGF, ICAM-1, and VCAM-1 positive structures between varicose and normal veins; however, it could be explained by the limitations of the study. CONCLUSIONS: Varicose GSVs represent nonhomogeneous integrity of the basement membrane, smooth muscle disorganization, and active neoangiogenesis, suggesting remodulation of blood vessels. Changes in the appearance of PGP 9.5-containing innervation, laminin, and collagen IV in tunica intima confirm the remodulation of damaged blood vessels.

Primary Leiomyosarcoma of the Great Saphenous Vein: Case Report and Review of the Literature.

Soft tissue sarcomas are very rare tumors, representing less than 1% of all cancers. Leiomyosarcomas are a rare group of them representing about 6% of soft tissue sarcomas and they involve smooth muscles. Less than 2% of all leiomyosarcomas involves large blood vessels. Leiomyosarcomas of vein tunica media are very rare (1/100,000 malignant cancers) and only 10% of these originate from the great saphenous vein. In this article, we report a clinical case that occurred in our institution and review all the literature available at now.

Levels of l-ascorbic acid and cadmium in the saphenous vein of patients with coronary artery disease are negatively correlated.

BACKGROUND: The aim of this study was the simultaneous determination of levels of cadmium and l-ascorbic Acid (AA) in human saphenous vein (SV) used in coronary artery bypass grafting (CABG) and check whether there is a relationship between these levels. METHODS: Human SV were collected from 40 patients (20 men and 20 women; age, 40-75 years) at the time of routine coronary artery surgical revascularization. The concentration of cadmium in the tissue was determined according to the GF AAS-atomic absorption method. The concentration of AA was assayed in supernatant by FIA method with spectrophotometric detection. RESULTS: AA concentration (mean±SD); men: 98,7±13,18µg/g tissue, women: 96,06±11,98µg/g tissue. Cadmium concentration(mean±SD); men: 309±103,71ng/g tissue, women: 348,5±255,71ng/g tissue. Correlations among concentrations of AA and cadmium were insignificant negative in the group of men (Pearson r=-0,1504, p=0,5269) and in the group women (Pearson r=-0339, p=0144). CONCLUSIONS: Negative correlations among concentrations of AA and cadmium in human SV obtained in our study may indicate a protective effect of this vitamin in relation to toxic cadmium.

Histological and immunohistochemical evaluation of human saphenous vein harvested by endoscopic and open conventional methods.

OBJECTIVES: The introduction of endoscopic saphenous vein harvesting (ESVH) has been reported to decrease saphenectomy-associated wound pain and infection, compared with the traditional open conventional saphenous vein harvesting (OCSVH) technique. Despite all these benefits, the rate of adoption among surgeons has been variable. Criticism of this technique centres on the risk of injury at the time of vein harvest with its potential detrimental effect on structural viability and long-term patency. The aim of our study is to investigate the endothelial preservation of saphenous vein grafts harvested by various extraction methods. METHODS: A prospective, observational study of 30 human saphenous vein grafts was performed to evaluate endothelial preservation by haematoxylin-eosin and CD 31 staining methods. The saphenous vein was harvested endoscopically either by an open tunnel (OT-ESVH), closed tunnel (CT-ESVH) or an OCSVH harvesting technique. Research samples were collected without distension to avoid intraluminal dilatation and endothelial disruption. Both haematoxylin-eosin and immunohistochemistry slides were imaged by a high-resolution slide-scanning system. RESULTS: Haematoxylin-eosin staining of the CT-ESVH group showed mostly preserved endothelium (P = 0.398) with some endothelial stretching (P = 1.0) and no endothelial detachment (P = 0.197). The OT-ESVH group showed marked endothelial stretching (P = 0.053). However, the OCSVH group showed significantly more endothelial detachment than the endoscopic groups (P = 0.01). The mean grading score of immunohistochemistry using the CD 31 antibody was much lower in the OT-ESVH group (1.6 ± 0.84, P = 0.009), showing more poorly preserved endothelial cells than the CT-ESVH and OCSVH groups. CONCLUSIONS: We observed more endothelial stretching in the OT-ESVH group, which in our opinion, was due to lack of subcutaneous tissue separation, poor visualization and traction stresses across the wall of the saphenous vein. However, the OCSVH method revealed poor endothelial protection with areas of endothelial detachment, not observed with both endoscopic techniques. Interestingly, most preserved endothelium was found in the CT-ESVH group, which was previously known to be associated with worse graft patency.

Evaluation of apoptosis in varicose vein disease complicated by superficial vein thrombosis.

BACKGROUND: The factors contributing to superficial vein thrombosis (SVT) in patients with varicose vein disease are unclear. Differences in vein wall apoptotic activity could be associated with the pathogenesis of SVT. The aim of the study is to address the role of the programmed cell death in the vein wall by comparing varicose veins with history of SVT to uncomplicated varicose veins. PATIENTS AND METHODS: Vein segments from the proximal part of the great saphenous vein (GSV), the distal part of the vein and from a varicose tributary, from 16 patients with varicose vein disease and one episode of SVT, were evaluated for the immunohistochemical expression of pro-apoptotic (Bax, p53, Caspase 3, BCL-6, BCL-xs), anti-apoptotic (BCL-xl and BCL-2) and proliferation (Ki-67) markers. The results of this study were compared to the results from the evaluation of 19 patients suffering from uncomplicated varicose vein disease and 10 healthy GSVs as controls. RESULTS: Overall, there was increased apoptosis in the distal part of GSV compared to the proximal part documented by increased expression of Bax (p < 0.01), Caspase 3 (p = 0.01), BCL-xs (p < 0.01). The comparisons of the markers' expression between patients with varicose veins and patients with a history of SVT showed significant differences among the three different anatomic locations. In the proximal GSV, only BCL-xs was higher in patients with SVT (p = 0.029). In the tributaries, Bax, BCL-xl and Ki-67 were higher in patients with SVT (p < 0.01). In the distal GSV, increased Bax, BCL-xs, BCL-xl and Ki-67 staining was observed in the thrombosis group compared to uncomplicated veins (p < 0.01). CONCLUSIONS: The vein wall in SVT shows increased pro-apoptotic activity compared to uncomplicated disease and normal veins. Whether increased vein wall cell apoptosis is a causative factor for SVT in varicose veins disease or a repairing mechanism of the thrombosis itself needs further research.

Pedicled no-touch saphenous vein graft harvest limits vascular smooth muscle cell activation: the PATENT saphenous vein graft study.

OBJECTIVE: Neointimal hyperplasia secondary to vascular smooth muscle cell (VSMC) activation limits the long-term patency of saphenous vein grafts (SVGs). We compared markers of vascular injury and VSMC activation in SVGs harvested using the pedicled 'no-touch' (NT) vs the conventional (CON) technique. METHODS: Patients undergoing coronary artery bypass surgery were enrolled in the PATENT SVG trial (clinicaltrials.gov NCT01488084). Patients were randomly allocated to have SVGs harvested with the NT technique from one leg and the CON method from the other. SVG segments underwent morphometry, histological and electron microscopy assessments and transcript measurements of VSMC activation and differentiation markers. Leg wound functional recovery and harvest site complications were assessed using a quality-of-life questionnaire. RESULTS: A total of 17 patients (65.3 ± 7.3 years) were enrolled. SVGs harvested using the NT vs CON technique exhibited preserved intimal, medial and adventitial architecture. CON harvest was associated with greater medial Kruppel-like factor 4 transcript levels (0.26 ± 0.05 vs 0.11 ± 0.02, P < 0.05). CON samples had significantly lower medial serum response factor (0.53 ± 0.11 vs 1.44 ± 0.50, P < 0.05) and myocardin (0.59 ± 0.08 vs 1.33 ± 0.33, P < 0.05) transcript levels. MicroRNA-145, an inhibitor of VSMC activation and differentiation, was higher in the NT vs CON samples (1.84 ± 1.03 vs 0.50 ± 0.19, P < 0.05). Leg assessment scores were worse in the NT legs at 3 months, but similar to CON scores at 12 months. CONCLUSIONS: SVGs harvested using the 'NT' technique exhibit an early molecular and morphological pattern consistent with decreased VSMC activation compared with CON harvesting. Functional leg recovery was similar in both groups at 12 months. Larger studies are required to corroborate these findings.

Cytokeratin 8 in venous grafts: a factor of unfavorable long-term prognosis in coronary artery bypass grafting patients.

BACKGROUND: Smooth muscle cells, present in the saphenous vein (SV) tunica media, may contribute to late occlusion of venous aortocoronary grafts. The aim of present study was to evaluate expression of selected cytoskeletal proteins in tunica media of SV grafts obtained from patients undergoing coronary artery bypass grafting (CABG) and correlate procured results to late venous graft failure observed in these patients. METHODS: The study involved 218 patients (mean age of 62.5 ± 8.7 years) who underwent primary isolated CABG with the use of at least one venous aortocoronary bypass graft. Expressions of alpha-smooth muscle actin, smooth muscle-myosin heavy chain, calponin and cytokeratin 8 in SV wall were estimated by means of immunohistochemistry. The primary clinical endpoint was defined as the presence of any coronary artery disease (CAD) progression symptom while angiographic one as significant stenosis in the venous graft. RESULTS: Thirty-eight (18.1%) patients have reached the primary clinical endpoint. Freedom from clinical CAD deterioration was 0.95 ± 0.02, 0.87 ± 0.03 and 0.83 ± 0.04, for 12-, 24-,36-month follow-up, respectively. Forty-four study participants have reached the angiographic endpoint. Multivariate logistic regression analysis revealed an increased expression of cytokeratin 8 accompanied by calponin under expression in SV tunica media were independent risk factors for venous graft failure. CONCLUSIONS: An increased expression of cytokeratin 8 and weak of calponin in tunica media of SV grafts might be useful markers of unfavorable long-term prognosis in CABG patients. In the future, assessment of their expression may enable to select the most appropriate candidates for SV grafts.

Assessment of vasa vasorum in the walls of thrombophlebitic saphenous vein.

AIM: The purpose of this study was to investigate the proliferation of vasa vasorum (VV) in the walls of thrombophlebitic saphenous vein (TSV), and to evaluate the influence of high venous pressure and lack of oxygen on the VV. METHODS: The specimens of the great saphenous vein were collected: 11 primary varicose vein (PVV), 11 TSV and, as a control, eight normal great saphenous vein. Masson staining and immunohistochemistry for CD34 were used to observe the status of VV, and the number of VV were counted under light microscopy. RESULTS: VV of the thrombophlebitic saphenous vein group (TSVG) were clustered together in adventitia, increased linearly in media, and scattered appearance in intima, were increased partially in intima of thrombus rupturing. In TSVG, the number of VV observed in adventitia, media and intima was 16.738±7.685, 4.845±2.537, 2.448±3.030, respectively. In the primary varicose vein group (PVVG), the corresponding values were 14.280±4.440, 2.965±1.125, 0.500±0.548. And the number was 8.911±2.629, 0.150±0.424, 0±0 in the control group (CG). Significantly higher numbers of VV were observed in the TSVG as compared to the PVVG or CG (P<0.05). No significant difference was observed between intima and media (P>0.05). CONCLUSION: Thrombi in varicose veins can induce proliferation of VV, which may be involved in high venous pressure and hypoxia.

Analysis of vascular endothelial growth factor gene expression in the tissues of patients with chronic venous insufficiency.

OBJECTIVE: Immunohistochemical techniques have revealed the presence of vascular endothelial growth factor (VEGF) in the epidermis of patients with chronic venous disease (CVD). Our objective was to perform a quantitative analysis of the VEGF gene transcription in tissues that are potential sources of this factor (skin, varicose veins [VV] and great saphenous vein [GSV]) in patients with CVD. METHODS: In all, 212 skin and venous tissue samples were collected from patients diagnosed with CVD and controls. The VEGF gene expression was analysed using quantitative realtime polymerase chain reaction (PCR). RESULTS: The skin VEGF expression was lower in the CVD group than in the control group (P = 0.04). There were no significant differences between the insufficient GSV of the CVD group and the control healthy vein (P = 0.22). There was a greater expression of VEGF in the VV of the CVD group than in the control healthy vein (P = 0.03). Comparison of the VEGF expression between the different tissue types in the CVD group revealed significant differences between the skin and GSV (P = 0.02) and between the skin and the VV (P = 0.004), and between the VV and the GSV (P = 0.02). CONCLUSIONS: The results of the present study show an over-expression of VEGF gene in the VV tissue of patients with CVD. Based on the data in patients with C2 disease, the VVs appear to be the source of increased VEGF expression.

α-Adrenoceptor assays.

α-Adrenoceptors mediate responses to activation of both peripheral sympathetic nerves and central noradrenergic neurons. They also serve as autoreceptors that modulate the release of norepinephrine (NE) and other neurotransmitters. There are two major classes of α-adrenoceptors, the α(1)- and α(2). Each class is subdivided into three subtypes: α(1A), α(1B), α(1D), and α(2A), α(2B), α(2C). Described in this unit are in vitro isolated tissue methods used to study α-adrenoceptor functions and to identify novel ligands for these receptors. Detailed protocols describing use of isolated tissues to study the various α(1)- and α(2)-adrenoceptor subtypes are provided.

In-vitro identification of distinctive metabolic signatures of intact varicose vein tissue via magic angle spinning nuclear magnetic resonance spectroscopy.

OBJECTIVES: Nuclear magnetic resonance (NMR) spectroscopy is an established tool for metabolic profiling of tissues or biofluids with utility in identifying disease biomarkers and changes in enzymatic or gene expression. This pilot study aims to compare the metabolic profiles of intact varicose and non-varicose vein tissue via magic angle spinning (MAS) NMR spectroscopy with a view to promoting the understanding of the pathogenesis of varicose vein formation. METHODS: Varicose vein tissue (n = 8) was collected from patients undergoing varicose veins surgery. Control non-varicose great saphenous vein samples were collected from patients undergoing lower limb amputation (n = 3) and peripheral arterial bypass surgery (n = 5). Intact tissue samples (average weight 10.33 ± 0.8 mg) from each vein segment were analysed using 1D MAS (1)H NMR (600 MHz) spectroscopy. For selected vein samples, two-dimensional (2D) NMR experiments were performed. Differences between spectra from varicose and non-varicose tissues were elucidated using a variety of multivariate statistical analyses. RESULTS: The metabolic profiles of varicose veins samples were clearly differentiated from non-varicose veins samples. Lipid metabolites were present at a higher concentration in the non-varicose veins group whilst creatine, lactate and myo-inositol metabolites were more characteristic of the varicose veins group. CONCLUSION: We demonstrate differential metabolic profiles between varicose veins and non-varicose veins. Elucidating the metabolic signature underlying varicose veins can further improve our understanding of the biological mechanisms of disease initiation, progression, and aid in identifying putative therapeutic targets.

Increased expression of hypoxia-inducible factor-1alpha and Bcl-2 in varicocele and varicose veins.

BACKGROUND: Primary vein wall abnormalities leading to secondary blood stasis and increased venous pressure that cause tissue hypoxia are observed in varicocele and varicose veins. Both types of diseased vessels are characterized by dilated thickened vein walls. Hypoxia upregulates Bcl-2 (antiapoptosis protein) expression in different human cell types. We studied the expression of hypoxia-inducible factor-1alpha (HIF-1α) and Bcl-2 in both venous diseases. METHODS: All vascular specimens, including the saphenous and internal spermatic veins, from patients with either varicocele or left inguinal herniorrhaphy (control group) were studied using immunoblotting, immunohistochemical staining, and double immunofluorescence staining. The data were analyzed using 1-way analysis of variance with Tukey comparison test. RESULTS: Protein analysis revealed that both venous diseases had a higher expression of HIF-1α and Bcl-2 compared with the control group (P < 0.05). Immunohistochemical staining and double immunofluorescence staining revealed that the greatest degree of HIF-1α and Bcl-2 colocalization occurred in the muscle layer of both diseased vessels. Moreover, under confocal microscopy, elevated Bcl-2 expression was found in the endothelium of both study groups compared with the control group. CONCLUSIONS: Our findings revealed increased expression of HIF-1α and Bcl-2 in varicocele and varicose veins and increased Bcl-2 expression especially in the endothelium under hypoxia. Thus, Bcl-2 overexpression may protect cells against apoptosis and contribute to the dilated thickened walls seen in both types of diseased vessels.

Endothelial preservation of the minimally manipulated saphenous vein composite graft: histologic and immunohistochemical study.

OBJECTIVE: We evaluated the efficacy of minimally manipulative surgical strategies to harvest the saphenous vein for use in a Y-composite graft based on the left internal thoracic artery in terms of preservation of endothelial structure and function. METHODS: Twenty patients who underwent off-pump coronary revascularization using the saphenous vein in a Y-composite graft based on the left internal thoracic artery were studied. The saphenous vein was harvested from each patient with minimal manipulation. An excess saphenous vein segment was removed before dilatation (control group), and a second segment was removed after dilation performed using a pressure-sensing syringe (conventional group). A third segment was obtained from a Y-composite vein graft dilated by flow and pressure from the left internal thoracic artery (composite group). Hematoxylin-eosin staining and immunohistochemistry using antibodies against CD31, CD34, von Willebrand factor, and endothelial nitric oxide synthase were performed. A generalized estimating equation was adopted for statistical analysis. RESULTS: Histologic and immunohistochemical studies revealed better endothelial preservation in the composite and control groups than in the conventional group (P < .01 in each). The composite group saphenous vein showed a lower grade of endothelial integrity than the control group saphenous vein based on hematoxylin-eosin staining, CD34 immunohistochemistry, and nitric oxide synthase staining (P < .001 in each). CONCLUSIONS: Harvesting of the saphenous vein using minimal manipulation for use in a Y-composite graft based on the left internal thoracic artery preserved endothelial structure and function when compared with manually dilated saphenous vein harvesting.

Loss of lymphatic vessels and regional lipid accumulation is associated with great saphenous vein incompetence.

OBJECTIVE: Recent studies suggest that biologic changes in the vein wall associated with varicose veins (VVs) occur not only in valvular tissue but also in nonvalvular regions. We previously used imaging mass spectrometry (IMS) to determine the distribution of lipid molecules in incompetent valve tissue. In this study, we used IMS to analyze incompetent great saphenous veins (GSVs) in patients with varicose vein (VV) to assess the distribution of lipid molecules. METHODS: We obtained GSV tissue from 38 VV patients (50 limbs) who underwent GSV stripping. For the control veins (CV), we obtained GSV samples from 10 patients undergoing infrainguinal bypass with reversed GSV grafting for peripheral artery occlusive disease (10 limbs). Conventional and immunofluorescence staining were performed for histopathologic examination. The total lipid content in the homogenized vein tissue was determined. The localization of each lipid molecule in the vein wall was assessed by IMS. RESULTS: The histologic examination showed the VV walls were significantly thicker than the CV walls, and only the VV adventitia was positive for lipid staining. The VV wall had higher concentrations of phospholipids and triglycerides than the CV wall. IMS revealed an abnormal accumulation of lysophosphatidylcholine (LPC; 1-acyl 16:0) and phosphatidylcholine (diacyl 16:0/20:4) in the VV intima and media. Triglyceride was found only in VV adventitia. The number of lymphatic vessels, as measured by staining with D2-40, a lymphatic vessel-specific marker, was significantly lower in the VV adventitia than in the CV adventitia. Lymphatic vessel reduction may be associated with insufficient lymphatic drainage in the VV adventitia causing histologic changes in VV tissue. CONCLUSIONS: The accumulation of LPC (1-acyl 16:0) and PC (diacyl 16:0/20:4) in the VV intima and media may be associated with chronic inflammation, leading to VV tissue degeneration. Furthermore, insufficient lipid drainage by lymphatic vessel may be responsible for accumulation of lipid molecules and subsequent vein wall degeneration.

Dysregulated gene expression of extracellular matrix and adhesion molecules in saphenous vein conduits of hemodialysis patients.

OBJECTIVE: The incidence of cardiovascular disease was approximately 10 times higher in hemodialysis patients with end-stage renal disease than in the general population. The saphenous vein is the most commonly used conduit for coronary artery bypass grafting. However, the extracellular matrix and adhesion molecule characteristics of saphenous vein in hemodialysis patients remain unclear. The aim of the present study was to survey the extracellular matrix gene expression profile of the saphenous vein in hemodialysis patients undergoing coronary artery bypass grafting. METHODS: A total of 34 patients undergoing elective coronary artery bypass grafting were enrolled. Of the 34 patients, 15 with end-stage renal disease required maintenance hemodialysis. The control group consisted of the other 19 patients without preoperative renal disease. Samples of the saphenous vein were obtained at coronary artery bypass grafting. The expression profile of the extracellular matrix genes was analyzed by microarray. The tissue matrix metallopeptidase/tissue inhibitor of metallopeptidase protein activities in the saphenous vein were evaluated by immunocytochemistry and Western blotting. RESULTS: Nineteen extracellular matrix and adhesion molecule-focused genes demonstrated at least a threefold difference in expression between the 2 groups. Upregulation was observed in 16 genes, and 3 genes appeared to be downregulated. Notable imbalanced matrix metallopeptidase/tissue inhibitor of metallopeptidase protein activities of saphenous vein exposed to end-stage renal disease conditions was found. CONCLUSIONS: The results from present study suggest that the native extracellular matrix gene expression profile of the saphenous vein conduits in hemodialysis patients show signs of the vein graft disease process before coronary surgery. Furthermore, some preoperative profiles of hemodialysis patients undergoing coronary artery bypass grafting might provide some useful clues regarding vein graft quality and prompt adjustment in surgical strategy.