Progression Of Vascular Lesions Research Articles

B-cells in pulmonary arterial hypertension: friend, foe or bystander?

There is an unmet need for new therapeutic strategies that target alternative pathways to improve the prognosis of patients with pulmonary arterial hypertension (PAH). As immunity has been involved in the development and progression of vascular lesions in PAH, we review the potential contribution of B-cells in its pathogenesis and evaluate the relevance of B-cell-targeted therapies. Circulating B-cell homeostasis is altered in PAH patients, with total B-cell lymphopenia, abnormal subset distribution (expansion of naïve and antibody-secreting cells, reduction of memory B-cells) and chronic activation. B-cells are recruited to the lungs through local chemokine secretion, and activated by several mechanisms: 1) interaction with lung vascular autoantigens through cognate B-cell receptors; 2) costimulatory signals provided by T follicular helper cells (interleukin (IL)-21), type 2 T helper cells and mast cells (IL-4, IL-6 and IL-13); and 3) increased survival signals provided by B-cell activating factor pathways. This activity results in the formation of germinal centres within perivascular tertiary lymphoid organs and in the local production of pathogenic autoantibodies that target the pulmonary vasculature and vascular stabilisation factors (including angiotensin-II/endothelin-1 receptors and bone morphogenetic protein receptors). B-cells also mediate their effects through enhanced production of pro-inflammatory cytokines, reduced anti-inflammatory properties by regulatory B-cells, immunoglobulin (Ig)G-induced complement activation, and IgE-induced mast cell activation. Precision-medicine approaches targeting B-cell immunity are a promising direction for select PAH conditions, as suggested by the efficacy of anti-CD20 therapy in experimental models and a trial of rituximab in systemic sclerosis-associated PAH.

The role of plateletcrit in Takayasu arteritis: A potential biomarker for disease activity and 6-month treatment response.

To determine the role of plateletcrit as a potential biomarker for disease activity and treatment response in Takayasu arteritis (TAK). Totally, 215 newly diagnosed TAK patients were consecutively enrolled. Demographic data, clinical manifestations, laboratory and imaging examinations, and treatment strategy were recorded at baseline and at each visit during the 6-month treatment period. Normal plateletcrit (0.1%-0.4%) and hyper-plateletcrit (>0.4%) observed at baseline were used as group criteria. At baseline, the overall plateletcrit was 0.32 (0.24-0.38)%, with a normal and high level observed in 172 (80.00%) and 43 (20.00%) patients, respectively. Baseline plateletcrit was significantly higher in patients with active disease and associated with inflammatory biomarkers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin (IL)-6 (all p < .01). At 6 months, complete remission was achieved in 171 (79.53%) patients, and a significant decrease in plateletcrit was observed in these cases (p < .01). Patients with a normal baseline plateletcrit were more likely to achieve complete remission compared to those with a high baseline plateletcrit (HR = 4.65, 95% CI: 2.38-19.08, p < .01). In addition, ESR (p = .01) and IL-6 (p = .02) levels were still higher in patients with a high baseline plateletcrit at 6 months. Progression of vascular lesions was indicated in 18 (8.37%) patients at 6 months, and these patients also had significantly higher baseline plateletcrit (p = .03). Plateletcrit levels were positively related to disease activity and inflammatory index in TAK. Importantly, patients with high baseline plateletcrit levels may show a worse treatment response at 6 months.

Sb-Phenyl-N-methyl-5,6,7,12-tetrahydrodibenz[c,f][1,5]azastibocine Induces Perlecan Core Protein Synthesis in Cultured Vascular Endothelial Cells.

Vascular endothelial cells synthesize and secrete perlecan, a large heparan sulfate proteoglycan that increases the anticoagulant activity of vascular endothelium by inducing antithrombin III and intensifying fibroblast growth factor (FGF)-2 activity to promote migration and proliferation in the repair process of damaged endothelium during the progression of atherosclerosis. However, the exact regulatory mechanisms of endothelial perlecan expression remain unclear. Since organic-inorganic hybrid molecules are being developed rapidly as tools to analyze biological systems, we searched for a molecular probe to analyze these mechanisms using a library of organoantimony compounds and found that the Sb-phenyl-N-methyl-5,6,7,12-tetrahydrodibenz[c,f][1,5]azastibocine (PMTAS) molecule promotes the expression of perlecan core protein gene without exhibiting cytotoxicity in vascular endothelial cells. In the present study, we characterized proteoglycans synthesized by cultured bovine aortic endothelial cells using biochemical techniques. The results indicated that PMTAS selectively induced perlecan core protein synthesis, without affecting the formation of its heparan sulfate chain, in vascular endothelial cells. The results also implied that this process is independent of the endothelial cell density, whereas in vascular smooth muscle cells, it occurred only at high cell density. Thus, PMTAS would be a useful tool for further studies on the mechanisms underlying perlecan core protein synthesis in vascular cells, which is critical in the progression of vascular lesions, such as those during atherosclerosis.

Diabetes mellitus associated neurovascular lesions in the retina and brain: A review.

Diabetes mellitus (DM) is now recognized as a system-wide, autoimmune, inflammatory, microvascular disorder, which, in the retina and brain results in severe multifocal injury now recognized as a leading cause, world-wide, of progressive vision loss and dementia. To address this problem, resulting primarily from variations in glycemia in the prediabetic and overt diabetic states, it must be realized that, although some of the injury processes associated with diabetes may be system wide, there are varying responses, effector, and repair mechanisms that differ from organ to organ or within varying cell structures. Specifically, within the retina, and similarly within the brain cortex, lesions occur of the "neurovascular unit", comprised of focal microvascular occlusions, inflammatory endothelial and pericyte injury, with small vessel leakage resulting in injury to astrocytes, Müller cells, and microglia, all of which occur with progressive neuronal apoptosis. Such lesions are now recognized to occur before the first microaneurysms are visible to imaging by fundus cameras or before they result in detectable symptoms or signs recognizable to the patient or clinician. Treatments, therefore, which currently are not initiated within the retina until edema develops or there is progression of vascular lesions that define the current staging of retinopathy, and in the brain only after severe signs of cognitive failure. Treatments, therefore are applied relatively late with some reduction in progressive cellular injury but with resultant minimal vision or cognitive improvement. This review article will summarize the multiple inflammatory and remediation processes currently understood to occur in patients with diabetes as well as pre-diabetes and summarize as well the current limitations of methods for assessing the structural and functional alterations within the retina and brain. The goal is to attempt to define future screening, monitoring, and treatment directions that hopefully will prevent progressive injury as well as enable improved repair and attendant function.

DIAGNOSTIC CRITERIA FOR UNDIFFERENTIATED CONNECTIVE TISSUE DYSPLASIA IN PATIENTS WITH ARTERIAL HYPERTENSION

The aim – to improve the diagnosis efficiency of patients with arterial hypertension (AH) combined with undifferentiated connective tissue dysplasia (UCTD) based on the study of clinical course, the severity of UCTD external and internal symptoms with determining the levels of IL-1, IL-6, TNF-a, free and general blood oxyproline.&#x0D; Material and Methods. The study implied examination of 90 patients (52 women and 38 men) with AH of stage 2 from first to third degrees with manifestations of UCTD, who were on inpatient treatment in the Cardiology Department of the Lviv City Communal Clinical Emergency Hospital. The mean age of patients was (61.14±2.58) years. Patients were divided into 3 groups depending on the stage and degree of hypertension. Group I (n=16) included patients with hypertension of the first degree, group II (n=35) – with AH of the second degree, group III (n=39) – with AH of the third degree. The control group consisted of 20 patients with hypertension without manifestations of CTD.&#x0D; Patients underwent clinical (checkup, palpation, percussion, auscultation), laboratory (determination of IL-1, IL-6, TNF-a, free and general oxyprolin blood levels) and instrumental studies (ECG, echocardiography, DBPM, ultrasound examination of internal organs and vessels of the lower extremities, ultrasound duplex examination of the carotid and vertebral arteries, radiological examination of the osteoarticular system), consultations of an ophthalmologist, neurologist, traumatologist and dentist.&#x0D; Results. As a result of the study, in the group I of patients (n=16) UCTD of slight degree of severity was revealed in 13 (81 %), of medium degree – in 3 (19 %) persons. In the group II of patients (n=35), UCTD of moderate severity was found in 30 (86 %), severe – in 5 patients (14 %). In the group III of patients (n=39), UCTD of moderate severity was found in 32 patients (82 %), severe – in 7 (18 %). In the study of the level of TNF-a, an increase compared to the control group was detected, particularly, in the group I of patients its level exceeded in 37.4 times, in the group II – in 39.6 times, in the group III – in 46.2 times (p&lt;0.001). IL-1b increased by 2.6-fold (р&lt;0.05) in the group I of patients compared to the control group, 3.1-fold (р&lt;0.01) – in the group II, and by 3.7-fold, that was the foremost (р&lt;0.001), in patients of the group III. In turn, IL-6 in the group I of patients exceeded the indicators of the control group by 4.3 times (p&lt;0.001), in the group II – 4.8 times (p&lt;0.001), in the group III – 5.7 times (р&lt;0.001). The study of the level of free oxyproline revealed its increase in comparison with the control group, namely in the group I of patients exceeded in 6.12 times, in the group II – in 6.81 times, in the group III – by 7.56 times (р&lt;0.01). The study of the general of bound oxyproline revealed its increase in comparison with the control group, namely in the group I of patients exceeded by 6.98 times, in the group II – by 7.79 times, in the group III – by 9.42 times (p&lt;0.01), which indicates an increase in fibrillogenesis and more pronounced destructive and inflammatory processes in connective tissue.&#x0D; Conclusions. Patients with AH of the stage 2 from first to third degrees with manifestations of UCTD have increased levels of IL-1, IL-6 and TNF-a, which are not only sensitive markers of inflammation, but also play an important role in the pathogenesis and progression of vascular lesions, occurrence and destabilization of atherosclerotic plaques and thrombotic vessels occlusion. The determination of blood oxyprolin in patients with hypertension combined with UCTD confirms the presence of CTD, namely the decay of collagen is more pronounced in patients with severe dysplasia.

Treatment of Takayasu arteritis

Despite advances in the diagnosis and treatment, the mortality rate of Takayasu arteritis (TAK) is still elevated even today. The diagnosis is often made after along time delay and the course of the disease is characterized by progressive structural vascular lesions. Recently, new recommendations for the management of large vessel vasculitis were published by the European League Against Rheumatism (EULAR). For induction of remission oral glucocorticoids (GC) are administered in an initial daily dose of 40-60 mg. As experience has shown that the cumulative GC demand in TAK is high, GC-sparing treatment with moderately potent immunosuppressants, such as methotrexate, azathioprine and mycophenolate mofetil is recommended from the time of initial diagnosis. In cases of arelapsing course, tocilizumab or tumor necrosis factor (TNF)-alpha inhibitors can be used as an additive off-label treatment. If vascular stenoses persist despite supposedly sufficient inflammation control and if these stenoses are symptomatic, vascular surgery or interventional treatment procedures can be indicated. Such revascularization or even surgical procedures for the treatment of aneurysms should be performed during phases of sufficient drug control of the vasculitis. In quite afew patients progressive vascular lesions continue to develop despite clinical and laboratory analytical remission. Due to the poor correlation of clinical symptoms and acute phase markers with the progression of vascular lesions, the distinction between active and inactive diseases is often achallenge in the clinical practice. Imaging studies can then support therapeutic decisions but are not yet formally and comprehensively validated in the long-term course of TAK.

A case of bilateral cervical internal carotid artery dissection following herpes zoster of the trigeminal nerve

A 62 year-old man, who was taking prednisolone for nephrotic syndrome, was diagnosed with herpes zoster of the trigeminal nerve and treated with oral valacyclovir. One month later, he reported pain from the right side of the head and vomiting. MRI revealed an acute infarction in the right frontal lobe and dissection of the internal carotid artery of the right cervix. Trauma or other potential triggers were not observed. In consideration of the preceding condition of varicella zoster virus infection, acyclovir was administered in addition to unfractionated heparin, but an intramural hematoma emerged in the left internal carotid artery. Furthermore, evidence showing progression of these lesions was found. On the fifth day, prednisolone was increased to 1 mg/kg/day, and progression of vascular lesions was not observed. This case may prove valuable because it suggests a relationship between cervical artery dissection and herpes zoster.

Hyperhomocysteinemia in patients with chronic kidney disease and its relationship with the functional status of the cardiovascular system

Chronic kidney disease (CKD) is an important medical, social and economic problem nowadays. Patients with CKD are known to have an increased risk of development and progression of cardiovascular diseases. However, the causes and pathogenesis of cardiovascular complications are not well understood. One of the recently recognized “non-traditional” risk factors for the increased development of cardiovascular pathology in severe stages of CKD is hyperhomocysteinemia (HHC). The article presents the results of study of HHC frequency in patients with different stages of CKD as well as the relationship between HHC and endothelial dysfunction and structural-functional status of the heart. The study involved 148 persons with different stages of CKD who underwent immunoenzyme determination of total plasma homocysteine (HC), echocardiography, carotid ultrasonograghy, endothelial function was assessed as well. It was found that among the patients with CKD, 26 (21.1%) had normal and 34 (27.7%) had subnormal HC levels, mild HHC was observed in 30 (24.4%) and moderate HHC – in 33 (26.8%) cases, i.e. the total number of patients with elevated HC level was 88.9%. It should be noted that no patients with normal HC level were found among those with stage four CKD as well as in dialysis patients. The increase of blood plasma HC level was actually proportional to the severity of renal failure, which in its turn led to the shift in the number of cases towards higher rank indices of HHC level. In particular, while there were no patients with HHC among those with CKD-I, more than 50% of such patients were found in the group with CKD-V. Reduced myocardial contractility and echocardiographic markers of left ventricular hypertrophy in patients with CKD were found to be closely associated with HC concentrations in blood plasma. The data presented clearly demonstrate strong inverse correlation between endothelial dysfunction indices and HC level. So, the endothelium-dependent brachial artery vasodilation in patients with CKD-IV was lower by 3.8 and 1.5 times compared with control group and CKD-III group, respectively, and endothelium-independent vasodilation of the brachial artery – by 2.4 and 1.9 times, respectively. Correlation analysis also confirmed that impaired endothelium-dependent and endothelium-independent dilation with high statistical significance inversely correlated with the level of HC in blood plasma. Thus, the population of patients with CKD is characterized by high HHC frequency, which is closely associated with cardiovascular disorders (endothelial dysfunction, structural and functional remodelling of the myocardium) and can be an important risk factor for the development of vascular lesions. We believe that adequate correction of HHC, including administration of folic acid preparations could reduce the progression of vascular lesions in patients with CKD.

Cysteine proteases in atherosclerosis.

Atherosclerosis predisposes patients to cardiovascular diseases, such as myocardial infarction and stroke. Instigation of vascular injury is triggered by retention of lipids and inflammatory cells in the vascular endothelium. Whereas these vascular lesions develop in young adults and are mostly considered harmless, over time persistent inflammatory and remodeling processes will ultimately damage the arterial wall and cause a thrombotic event due to exposure of tissue factors into the lumen. Evidence from human tissues and preclinical animal models has clearly established the role of cathepsin cysteine proteases in the development and progression of vascular lesions. Hence, understanding the function of cathepsins in atherosclerosis is important for developing novel therapeutic strategies and advanced point of care diagnostics. In this review we will describe the roles of cysteine cathepsins in different cellular process that become dysfunctional in atherosclerosis, such as lipid metabolism, inflammation and apoptosis, and how they contribute to arterial remodeling and atherogenesis. Finally, we will explore new horizons in protease molecular imaging, which may potentially become a surrogate marker to identify future cardiovascular events.

Biglycan expression, earlier vascular damage and pro-atherogenic profile improvement after smoke cessation in young people

Background and aimsYoung cigarette smokers may already present with early signs of vascular inflammation and damage; biglycan (BGN) has been shown to play a critical role in the initiation and progression of vascular lesions, also in young smokers. We investigated whether after smoke cessation, monocyte BGN expression is reduced; moreover, we evaluated any improvement of pro-atherogenic profile and arterial stiffness (AS), and their relationship with BGN in abstinent smokers. MethodsTwo-hundred-fifty-one young people who had decided to quit smoking were enrolled; of these, 71 had completed the 12-month observation period maintaining smoking abstinence. At enrollment and 12 months later, we evaluated anthropometrics, laboratory profile, carotid-femoral pulse wave velocity (cf-PWV), carotid intima-media thickness (cIMT), BGN expression. ResultsAfter 12-month smoke abstinence, we found a significant decrease in inflammatory markers (Hs-CRP: −23.3%; fibrinogen: −11.8%; IL-6: −9.2%), and increased HDL-C levels (+9.3%); blood pressure values were also slightly reduced. cf-PWV (−8.9%) appeared to be improved; cIMT remained unchanged. BGN expression appeared to be reduced (−42.8% relative reduction). BGN reduction appeared to be associated with fibrinogen reduction, and smoking burden. Reduced cf-PWV appeared to be dependent on change in fibrinogen, SBP, IL-6, and BGN by multiple regression analysis. ConclusionsAfter the first year of smoke abstinence, the levels of IL-6, CRP, fibrinogen, HDL-C, and BGN expression, as well cf-PWV, are significantly improved as compared to baseline. This is the first evidence that removing exposure to a well-known cardiovascular risk factor, such as cigarette smoking, leads to significant reduction of BGN expression.

Abstract 3002: ID3 expression and oxidative DNA damage are associated with growth of benign and malignant vascular lesions

Abstract Higher levels of Id3 expression have been reported in tumor-infiltrating blood vessels from various tumors, but the exact role of Id3 in vascular lesion formation is poorly understood. This study aims at identifying the status of Id3 expression and distribution in benign vascular lesions and attempts to correlate this information with the progression of vascular lesion. In this study we investigated the expression pattern of Id3 in malignant, benign, and normal human vascular tissue specimens. Expression analysis of Id3 was carried out using immunohistochemical analysis in 48 sporadic samples of a heterogeneous group of benign and malignant vascular tissue. Immunohistochemical analysis confirmed that many of the malignant vascular lesions exhibited strong Id3 expression that correlated positively with increased 8-hydroxydeoxyguanosine (8-OHdG) a marker of oxidative DNA damage. In contrast, in normal human vascular tissue, Id3 expression and 8-OHdG was low. In malignant vascular tissue, Id3 protein displayed a stronger nuclear localization when compared to the cytoplasm. Id3 expression levels in benign vascular lesions while still expressing Id3 were to a lesser extent when compared to malignant vascular tissue. To our knowledge, this is the first study to compare benign and malignant vascular lesions to assess the role of Id3 and 8-OHdG. Our data reveals Id3 expression and oxidative DNA damage to be highly associated in malignant cells and to a lesser extent in their benign counterparts, indicating that the growth of vascular lesions may require oxidative stress signaling converging on Id3. The results also support the involvement of Id3 in tumor angiogenesis a process that critically influences the malignant behavior of cancer cells. Citation Format: Quentin H. Felty, Jayanta K. Das. ID3 expression and oxidative DNA damage are associated with growth of benign and malignant vascular lesions. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3002. doi:10.1158/1538-7445.AM2014-3002

Милдронат® — лечение кардионеврологической патологии в условиях ишемии и гипоксии

Цереброваскулярная патология уже давно перешла из разряда отдельно взятой медицинской проблемы в проблему социальную. Прогрессирование сосудистого поражения головного мозга приводит к значительному ограничению трудоспособности, а на поздних стадиях нарушает способность к самообслуживанию и значительно снижает качество жизни пациента. Ключевым звеном повреждения мозга является ишемический, или глутаматный, каскад, который многие исследователи считают триггером эксайтотоксического повреждения и главной причиной гибели нейронов. Одним из важных компонентов эффективной коррекции последствий ишемических нарушений является комплексная нейроцитопротекторная терапия. Для коррекции последствий как острой, так и хронической ишемии мозга необходимо эффективно воздействовать одновременно в нескольких направлениях, нормализуя метаболические изменения, устраняя цитокиновый дисбаланс, транскрипционные нарушения, снижая выраженность оксидативного стресса и эксайтотоксичности.

The role of sex steroids on cellular events involved in vascular disease

In this work we checked the hypothesis whether estrone, progesterone, and testosterone are able to modulate the interactions between platelets, monocytes, and endothelial cells either under basal or inflammatory conditions. Using adhesion assays we demonstrated that pretreatment of endothelial cells with estrone, progesterone, or testosterone prevented monocytes and platelets adhesion induced by the proinflammatory agent bacterial lipopolysaccharide. The hormones reduced the expression of mRNA of ICAM-1, VCAM-1, and P-selectin, endothelial surface proteins that mediate monocytes and platelets adhesion respectively. Integrins are the main leukocyte proteins that allow firm adhesion. Using flow cytometry we showed that estrone treatment of monocytes reduced CD11b and CD11c expression, either under basal or injury (lipopolysaccharide) conditions. The three steroids inhibited platelet aggregation in a nitric oxide dependent manner. Platelet function was not affected by the steroid treatment. The molecular mechanisms of action exerted by the steroids included the participation of the intracellular signaling pathways PKC, MAPK, and PI3K, which selectively and differentially mediate the stimulation of nitric oxide release. We evidence that estrone, progesterone, and testosterone modulate monocyte and platelet adhesion to endothelial cells, events that play a major role in the initiation and progression of vascular lesions. The steroid action was evidenced under basal or inflammatory conditions. The mechanisms of action exerted by the steroids included stimulation of nitric oxide production and the participation of PKC, MAPK, and PI3K systems.

Association of fetuin-A and cardiac calcification and inflammation levels in hemodialysis patients

Background. Vascular calcification is commonly found in chronic kidney disease (CKD) patients and it is one of the predictors of cardiovascular death. Recently, several studies have demonstrated that low fetuin-A levels are associated with mortality in uremic patients. Objectives. To investigate the importance of non-traditional risk factors of calcification including fetuin-A, IL-6 and high sensitivity CRP (hsCRP) in hemodialysis patients and their relationship to the extent of cardiac calcification by means of multislice computed tomography (MSCT), and echocardiography. Patients and methods. The study was conducted on 70 hemodialysis patients as well as 20 healthy control subjects. All patients were subjected to MSCT for evaluation of calcium score in the coronary arteries as well as echocardiography for detecting valvular calcification. In addition, the patients were sampled for evaluation of inflammatory markers such as hsCRP and IL-6 and also fetuin-A. Results. Mean serum fetuin-A was significantly lower in hemodialysis patients than controls subjects. By dividing the patients into tertiles of serum fetuin-A, a significant association between low levels of fetuin-A and high calcium score and valvular calcification were found. Multiple regression analysis showed that calcium scoring and IL-6 were the most independent risk factors for serum fetuin-A levels. Conclusion. Serum fetuin-A showed important association with coronary, valvular calcification and inflammation in hemodialysis patients. Assessment of both cardiac calcification and serum levels of fetuin-A may be of value to identify those subjects at higher risk of development and progression of vascular lesion and may be a novel therapeutic approach.

Pharmacological modulation by celecoxib of cachexia associated with experimental arthritis and atherosclerosis in rabbits

Non-steroidal anti-inflammatory drugs improve inflammatory cachexia in several conditions. Thus, we have explored inhibition of cyclooxygenase-2 (COX-2) in an experimental model of rheumatoid cachexia in rabbits. Chronic arthritis was induced in immunized rabbits by repeated intra-articular injections of ovalbumin. To increase the degree of systemic inflammation and also to induce atherosclerotic lesions, the animals were fed a hyperlipidaemic diet (2% cholesterol and 6% peanut oil) and were given an endothelial injury of the femoral artery. Rabbits were randomized to receive the COX-2 inhibitor celecoxib (10 mg·kg⁻¹ ·day⁻¹) or no treatment. After 4 weeks, sera, peripheral mononuclear cells and vessel specimens were collected. Inhibition of COX-2 by celecoxib modulated the systemic inflammatory response and increased total cholesterol and triglyceride levels. Celecoxib also minimized weight loss and prevented serum albumin fall. At a vascular level, celecoxib reduced COX-2 protein in the femoral arterial wall, but did not modify size or the macrophage infiltration of femoral lesions nor the percentage of rabbits with spontaneous aortic plaques. Our animal model induced a severe inflammatory cachexia, comparable to that of persistently active rheumatoid arthritis. The inhibition of COX-2 by celecoxib improves this state, suggesting that COX products play an important role in its development, without affecting the development or the progression of vascular lesions. Overall, these results suggest that celecoxib might be considered as a new therapeutic tool for the treatment of rheumatoid cachexia.

Improvement of experimental accelerated atherosclerosis by chondroitin sulphate

The rheumatic diseases have been associated with accelerated atherosclerosis. Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by persistent synovial inflammation which leads to disability and structural changes in joints. Epidemiological studies have demonstrated an increased cardiovascular mortality in patients with RA. In these patients, atherosclerotic plaque occurs earlier, and it has a faster evolution than in general population. Atherosclerosis (AT) is also an inflammatory disease partly mediated by cytokines, many of them involved on chronic synovitis. Our group has developed a rabbit experimental model of AT aggravated by chronic arthritis to study inflammatory mechanisms involved on the progression of vascular lesions and their response to drugs. A preliminary study using this model suggests a beneficial effect of chondroitin sulphate (CS), a drug recommended for the treatment of osteoarthritis, in controlling AT lesions. Yet clinical trials should be conducted with this compound to address the same hypothesis in human studies.

Effects of serum deprivation on the mechanical properties of adherent vascular smooth muscle cells

Vascular smooth muscle cell (VSMC) function plays a key role in regulating the development and progression of vascular lesions. Among the more significant phenomena that occur during the development of these lesions is the phenotypic switching of VSMCs from a contractile to a synthetic state. A better understanding of the concurrent changes to VSMC mechanical properties that occur with phenotypic shifts can help to elucidate the role of VSMC mechanics in the development of vascular diseases. In the current study, the mechanical properties of adherent cultured rat aortic VSMCs were assessed by atomic force microscopy. Serum starvation was used to induce a phenotypic shift in vitro. It was concluded that serum starvation led to a statistically significant increase in apparent elastic modulus after 5 days, as well as a statistically significant decrease in hysteresis after culture for 3 days. If this trend of VSMC mechanical properties changing concurrently with phenotypic shifts were to hold true in vivo, such changes could affect the processes of mechanotransduction and/or arterial mechanical properties, thereby contributing to the progression of vascular disease.

Proteoglycan as a Key Molecule in Atherosclerosis Progression: Characteristics of the Structure and Regulation of the Synthesis

Proteoglycans are macromolecules comprising a core protein and one or more glycosaminoglycan side chains. The macromolecules particularly derived from vascular smooth muscle cells accumulate in atherosclerotic vascular wall and are involved in the progression of vascular lesions. However, the functions of proteoglycans depend on the type of core proteins and microstructure of glycosaminoglycan chains, suggesting importance of the regulation of proteoglycan synthesis in vascular smooth muscle cells. Although the regulation of glycosaminoglycan chain formation is not clear, core protein synthesis is regulated by growth factors/cytokines, mechanical strain, coagulation factors, and other factors. Recently, we found that adiponectin, an adipose-specific plasma protein that exhibits antiatherogenic activities, regulates proteoglycan synthesis in vascular smooth muscle cells.

The role of matrix metalloproteinases in the development of vascular complications of diabetes mellitus – clinical implications

Cardiovascular complications are the leading cause of increasing and premature mortality in diabetic patients. Matrix metalloproteinases (MMPs) play an important role in the development and progression of vascular lesions. Matrix metalloproteinases are members of endopeptidases and are capable of degrading many extracellular matrix components. Results of recent studies indicated that non-pharmacological and pharmacological treatment of diabetes influenced disturbed system of metalloproteinases and their inhibitors. Clinical trials are being performed in hope that the selective MMP inhibitors reduce the progression of pathological vascular remodeling in diabetes. Further basic and clinical research is required to confirm hypothesis.

Pre-clinical atherosclerosis evaluated by carotid artery intimamedia thickness and the risk factors in children

Atherosclerosis as a cardiovascular disease was found to begin even in the fetal period. However, information about risk factors of pre-clinical atherosclerosis in childhood has been limited. Hence, this study was aimed to find out the risk factors of atherosclerosis by measuring the carotid artery intima-media thickness in children. High resolution B-mode ultrasound used to examine the carotid artery intima-media thickness was demonstrated to be useful in finding the early carotid structural changes. The study included 79 children who were divided into two groups according to their ages: group I consisted of 42 children with ages from 5 to 9 years and group II consisted of 37 children with ages from 10 to 18 years, Among them, 23 had a positive family history for risk, such as hypertension, obesity or dyslipidemia. Blood samples were collected and total cholesterol, triglycerides, high density lipoprotein and low density lipoprotein were assayed. The carotid artery intima-media thickness was measured by ultrasound. Comparisons were done between the two groups using Student's t tests and Chi-square analysis. Body mass index, blood pressure, levels of lipids, family history and the carotid artery intima-media thickness were calculated by conditional logistic regression analysis. Compared with the children without a positive family history, the incidence of the increased carotid artery intima-media thickness was significantly high (chi(2) = 4.364, P < 0.05). There were no statistically significant differences between left and right carotid arteries in carotid artery intima-media thickness (P > 0.05). In this study, diastolic blood pressure and the atherosclerosis index were suggested to be the risk factors to the thickened carotid artery intima-media thickness. In group I the diastolic blood pressure's odds radio was 1.187 (P = 0.035) and the atherosclerosis index odds radio was 37.165 (P = 0.001); in group II the diastolic blood pressure's odds radio was 1.371 (P = 0.009) and the atherosclerosis index odds radio was 30.724 (P = 0.015). The diastolic blood pressure and atherosclerosis index were the risk factors in pre-clinical arthrosclerosis. Regularly monitoring the high-risk children for the development and progression of vascular lesion would be of great value in avoiding and preventing cardiovascular disease.