Type III collagen in not usually found in jugular veins--this change to the adventitia happens in chronic venous disease."The IJVs of MS patients presenting a focal thickening of the vein wall are characterized by the prevalence of loosely packed type III collagen fibers in the adventitia."
If inflammatory marker expression is not observed, then these changes in the veins are not likely to be due to inflammation, which would mean it is not a likely result of any inflammatory processes going on in the central nervous system as part of MS.The extracranial veins of MS patients showed focal thickenings of the wall characterized by a prevailing yellow–green birefringence (corresponding to thin, loosely packed collagen fibers) correlated to a higher expression of type III collagen. No differences in cytoskeletal protein and inflammatory marker expression were observed.
Has anyone taken a look at Figure 2 yet? Does it show IJVs from patients who have had ballooning for CCSVI, and that is what's meant as treated IJV? Do the untreated and treated IJVs look about the same for collagen, and it's the healthy controls that is the far right figure that shows very different collagen composition?Fig. 2. Evaluation of the percentage of the orange–red (red bars) and yellow–green (green bars) birefringence/total birefringent area (A) and RI (B) in the different vein specimens. RI=yellow–green area/orange–red area. Untreat.=untreated IJV; treat.=treated IJV.
so, you can see--there are many things to consider in venous disease. Gender, genetics, blood group, lifestyle, etc. But the links to remodeling in the IJVs and MS are striking.Varicose vein disease is expressed very differently from one person to another, in terms of familial background, gender, society, and lifestyle. This is not surprising when we consider the large number of factors that predispose to and promote varicose veins.
• Ethnic group: the differences observed tend to be related to types of physical activity, which in this context correspond to the role attributed to prolonged VHT.
• Age: acts through the duration factor.
• Female gender: the influence of hormones on the venous wall is plausible, although difficult to demonstrate, but women with varicose veins have a later menopause. The role of pregnancy is clear, and emphasizes the need for prevention by compression therapy.
• Height and weight: height is a demonstrated risk factor, while obesity is not an independent factor. Nevertheless, excess weight increases the risk of leg ulcer.
• Manual work: a relationship exists between VHT and uncomfortable physical activity in a prolonged standing position.
• Genetics: a family link has been confirmed in several studies, including a well-known investigation by Cornu-Thénard et al,38 who also reported links to blood group and HLA type.
Hereditary abnormalities in elastin are obviously a cause of varicose veins, as in Marfan disease. There are also abnormal lines of fibroblasts that secrete defective categories of collagen or elastin. Prothrombogenic conditions develop during the course of varicose vein disease, with a propensity to hypofibrinolysis and hypercoagulability.39,40
The existence of vascular changes in the cerebral veins of MS patients has long been recognized [4], although it has not been ascertained whether these changes play a role in MS pathogenesis [14] or are just secondary to immunological abnormalities [6].
CCSVI, a syndrome characterized by an impaired brain drainage due to stenosis or obstruction of the IJV and/or the azygos veins, has been linked to MS [5]; the venous abnormalities have been ascribed to development defects during vascular trunk formation [15]. With the exception of a short report describing macroscopic lesions in the veins of two MS patients [16], at present, the histopathology of extracranial venous wall in MS patients has not been investigated.
Our results show for the first time an involvement of the IJVs in MS patients characterized by an altered proportion of collagen I and III within the adventitia.
Our results demonstrate that extracranial vein lesions of MS patients are characterized by a ratio of collagen type I/III similar to that observed in fibrotic lesions but without the presence of MFs, thus suggesting a local malformative pathogenesis rather than a fibrotic one; these results were confirmed by collagen type I and III immunohistochemistry.
Moreover, since the diseased-treated IJV specimens were sampled from vessel segments distal to the site of previous balloon venoplasty, it is unlikely that the altered collagen type I/III ratio results from local vessel trauma. Although mean age was higher in control compared with MS patients (80.3±2.8 vs. 33.8±3.3), the collagen changes were observed only in the veins of the younger MSpatients; this argues for a disease-associated rather than for an age related process.
A similarly altered collagen distribution has been described in several apparently unrelated conditions: varicose saphenous veins [27], hemorrhoids [28], paraesophageal hernia [29], skin incisional hernia [30], recurring inguinal hernia [31], and recurring hernia after alloplastic repair [32]. It is noteworthy that the venous ECM alterations seen in varicose vein patients are paralleled by similar changes in the dermis connective tissue, thus suggesting a systemic involvement of connective tissue [33]. Lower collagen type I/III ratio has also been associated with impaired anastomotic colon healing after surgery in humans [34] and in a rat model [35] as well as with increased wall stiffness and loss of compliance in dysfunctional bladders [36,37]. Moreover, in the developing bovine bladder, the percentage of type III collagen inversely correlates with bladder compliance [38].
The absence of inflammatory cells within the vein wall lesions suggests that the altered collagen I/III ratio is not secondary to an inflammatory disorder.
We suggest that the alterations observed in the adventitia of the IJVs of MS patients belong to a large group of conditions characterized by an altered collagen type I/III ratio, mainly due to a relative increase in type III collagen deposition.
cheer, correction....the collagen is in the elastic components of the vein. These are the media and advential. The endothelial layer is mostly intimal cellscheerleader wrote:Altered collagen expression in jugular veins in multiple sclerosis--Type III collagen in not usually found in jugular veins--this change to the endothelium happens in chronic venous disease."The IJVs of MS patients presenting a focal thickening of the vein wall are characterized by the prevalence of loosely packed type III collagen fibers in the adventitia."
http://linkinghub.elsevier.com/retrieve ... 592?via=sd
(please remember, I'm only a civilianWe suggest that the alterations observed in the adventitia of the IJVs of MS patients belong to a large group of conditions characterized by an altered collagen type I/III ratio, mainly due to a relative increase in type III collagen deposition.
Moreover, since the diseased-treated IJV specimens were sampled from vessel segments distal to the site of previous balloon venoplasty, it is unlikely that the altered collagen type I/III ratio results from local vessel trauma. Although mean age was higher in control compared with MS patients (80.3±2.8 vs. 33.8±3.3), the collagen changes were observed only in the veins of the younger MSpatients; this argues for a disease-associated rather than for an age related process.
http://www.ncbi.nlm.nih.gov/pubmed/3233351In 200 dissections of internal jugular veins, the valves were investigated with regard to their constitution, their macroscopic and their microscopic anatomy. In 88% of the cases, an ostial valve was found. The cusp of each consists of two parts in 77%, of only one part in 16%, and in 7% of three parts. In 12% these valves are not found. The structure, the configuration, the topography of these valves are explained. The stroma of the valve consists of collagen and elastic fibrils. The surface of the luminal and parietal part is covered by endothelial cells with elastic and muscular fibers close to the attachment of the cusp to the vein wall.
If so then it would not be likely to be a systemic collagen disease. This would be better news.Could the dilation above the valvular stenoses result in deposition of Type III collagen?
This was mentioned in Dr. Zamboni's paper, that patients with varicose veins also had abnormal collagen synthesis in their skin as well, thus suggesting a syystemic collagen abnormality. This should be testable in MS patients in the same way to see what the collagen composition of our dermal fibroblasts is. If our skin has abnormal collagen synthesis, that would suggest that we have a systemic collagen disorder. If our skin does not have abnormal collagen synthesis, that would suggest that our issues are more localized to the specific diseased veins. Either way it would add to what is known.Synthesis of Collagen Is Dysregulated in Cultured Fibroblasts Derived From Skin of Subjects With Varicose Veins as It Is in Venous Smooth Muscle Cells
Abstract
Background— The dilatation and tortuosity observed in varicose veins provide evidence for progressive venous wall remodeling associated with abnormalities of smooth muscle cells and extracellular matrix. The present study was designed to examine if the phenotypic modulations observed in the venous smooth muscle cells of patients with varicose veins were also present in their dermal fibroblasts.
Methods and Results— Collagen type I (collagen I), type III (collagen III), and type V (collagen V) were compared in dermal fibroblasts derived from the skin of control subjects and patients with varicose veins. The synthesis of collagen I, the release of its metabolites, and the expression of its mRNA were increased in fibroblasts from patients with varicose veins, whereas the synthesis of collagen III was decreased but not correlated with a decrease in mRNA expression and in metabolite release. Matrix metalloproteinases (MMP1, 2, 7, 8, 9, and 13) and their inhibitors (TIMP1 and 2) were quantified in both cell types; only the production of proMMP2 was increased in cells derived from patients with varicose veins.
Conclusions— These findings suggest that the synthesis of collagen I and III is dysregulated in dermal fibroblasts derived from patients with varicose veins. These results are comparable with those observed in smooth muscle cells derived from varicose veins, thus suggesting a systemic alteration of tissue remodeling in subjects with varicose veins.
I don't know if we're jumping to contusions or if I don't understand the reasoning. I still see no reason the process could not be age-related. Maybe the chnges happen when you are young. Maybe the things you have to have are youth and CCSVI. Can anybody un-confuse me?we were the ones who had the altered collagen in our veins, and those spritely 80-year-olds did not.
The way I understand it is that these changes are not something that is present in older people who do not have MS. The changes are present in young people with MS. It could still worsen as those young people with MS become old people with MS but it is not in itself age-related because the 80-year-olds without MS did not have the abnormal collagen.1eye wrote:I don't know if we're jumping to contusions or if I don't understand the reasoning. I still see no reason the process could not be age-related. Maybe the chnges happen when you are young. Maybe the things you have to have are youth and CCSVI. Can anybody un-confuse me?
If inflammatory marker expression is not observed, then these changes in the veins are not likely to be due to inflammation, which would mean it is not a likely result of any inflammatory processes going on in the central nervous system as part of MS.