transforming-growth-factor-beta and Varicose-Veins

Despite the high prevalence of varicose veins and the recent surge in research on the condition, the precise mechanisms underlying their development remain uncertain. In the past decade, there has been a shift from initial theories based on purely mechanical factors to hypotheses pointing to complex molecular changes causing histologic alterations in the vessel wall and extracellular matrix. Despite progress in understanding the molecular aspects of venous insufficiency, therapies for symptomatic varicose veins are directed toward anatomic and physical interventions. The present report reviews current evidence identifying the underlying biochemical alterations in the pathogenesis of varicose veins.

Topics: Biomarkers; Genetic Predisposition to Disease; Genomics; Humans; Muscle, Smooth, Vascular; Risk Factors; Transforming Growth Factor beta; Varicose Veins

This study aims to investigate potential differences in the presence of Transforming Growth Factor-Beta 1 (TGF-β1) between the vein walls of patients with varicocele and those of healthy individuals.. The study comprised a total of 40 participants, divided into two groups. The control group (Group 1) consisted of 20 patients who underwent coronary bypass surgery, while the varicocele group (Group 2) included 20 patients scheduled for varicocelectomy. The cytoplasmic and nuclear staining patterns of TGF-β1 immunohistochemistry were assessed in tissue samples under light microscopy, identifying any differences in TGF-β1 presence between varicocele patient vein walls and normal (saphenous) veins.. The varicocele group demonstrated lower nuclear and cytoplasmic TGF-β1 staining rates compared to the control group. After controlling for the independent factor of age, significantly lower nuclear and cytoplasmic staining was still observed in the varicocele group.. This study is the first of its kind to compare TGF-β1 staining in the vein walls of varicocele patients and healthy individuals. Previous studies focusing on varicose veins reported elevated TGF-β1 expression. Contrarily, our study observed lower TGF-β1 expression in varicocele patient veins, marking a unique contribution to the field.

Topics: Humans; Male; Saphenous Vein; Transforming Growth Factor beta; Transforming Growth Factor beta1; Varicocele; Varicose Veins; Vascular Surgical Procedures

Extracellular matrix remodeling in the vein wall is involved in varicose vein pathogenesis, with transforming growth factor beta(1) (TGF-beta(1)) playing a potential role. The aim of the study was to assess the TGF-beta signaling pathway including its receptor (TGF-beta RII) and phosphorylated receptor-regulated Smads (p-Smad2/3) in varicose veins.. Varicose veins from patients undergoing varicose vein surgery were the studied material, whereas normal greater saphenous veins from patients undergoing infrainguinal arterial bypass surgery were the control material. Expression of TGF-beta RII mRNA was assessed with RT-PCR, whereas expression of TGF-beta RII and p-Smad2/3 proteins was assessed with Western blot.. A significantly increased TGF-beta RII mRNA level was found in varicose veins (287 +/- 24%), when compared with normal veins (100 +/- 26%). The receptor protein expression reflected a changed mRNA level with significantly increased TGF-beta RII protein in varicose veins (290 +/- 21%), when compared with controls (100 +/- 16%). Enhanced TGF-beta RII expression was accompanied by increased p-Smad2/3 protein expression in varicose veins (257 +/- 19%) in comparison with normal veins (100 +/- 9%).. Increased TGF-beta RII expression and activation in the wall of varicose veins may be involved in extracellular matrix remodeling related to TGF-beta(1) and supports its role in the disease pathogenesis.

Topics: Adult; Blotting, Western; Carrier Proteins; Case-Control Studies; Female; Gene Expression; Humans; Male; Middle Aged; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; RNA, Messenger; Saphenous Vein; Signal Transduction; Smad2 Protein; Transforming Growth Factor beta; Transforming Growth Factor beta1; Varicose Veins

Transforming growth factor-beta 1 (TGF-beta 1 ) is known to maintain a balance between apoptosis and cellular dysfunction and therefore may have a pivotal role in vessel remodeling during pathogenesis of vascular disorders. We previously demonstrated that inducible nitric oxide synthase (iNOS) mediates signal transduction in vascular wall during the development of varicose veins. Currently, we investigated the expression and correlation of TGF-beta 1 , iNOS, monocyte/macrophage infiltration, and loss of vascular smooth muscle cells (VSMCs), in a series of normal and varicose vein specimens.. Twenty varicose vein specimens were retrieved from 20 patients undergoing lower-extremity varicose vein excision, and 27 normal greater saphenous vein segments (controls) were obtained from 27 patients undergoing infrainguinal arterial bypass surgery. Principal risk factors (diabetes mellitus, hypertension, tobacco abuse) were also compared. Varicose vein segments were separated into tortuous and nontortuous regions based on their macroscopic and microscopic morphology. VSMC actin, CD68 + monocytes/macrophages, iNOS, and TGF-beta 1 , were examined by immunohistochemistry, immunoblotting, and real-time reverse transcriptase polymerase chain reaction.. According to the CEAP classification for chronic lower extremity venous disease, most of the patients were in class 2 for clinical signs of the disease (n = 11). Mean ages were 53.6 +/- 4.7 years for the varicose vein group and 56.5 +/- 4.4 years for the controls. The gender distribution was same in both groups. Immunoreactivity to TGF-beta 1 and iNOS was significantly different in the tortuous regions of the varicose veins compared with nontortuous regions (P < .01). Not only was a significantly higher expression of iNOS noted in the varicose vein group (P < .001), but a differential expression of iNOS was also observed in the tortuous and nontortuous portions of the varicose veins. Significant overexpression of TGF-beta 1 (P < .01) that correlated with overproduction of iNOS and with increased presence of CD68 + monocytes/macrophages was observed in the varicose vein walls compared with normal veins.. This is the first evidence of TGF-beta 1 , as well as iNOS, being differentially upregulated in nontortuous and tortuous segments of varicose veins. The increased expression of TGF-beta 1 and presence of macrophages, correlating with overproduction of iNOS, may be associated with varicosity development and deserves further study.. The pathogenesis of varicose veins, the most common manifestation of chronic venous disease, is debatable. Elucidation of mechanisms involved in the disease process is the first step to improved therapeutic modulations. Towards this goal, the relationship between NO production and TGF-beta 1 in the molecular pathophysiology of chronic venous disease was investigated. The data identify for the first time, an important role for TGF-b1-iNOS-monocyte/macrophage signaling in the etiology of varicosities. Furthermore, we determine if there are any significant differences within the varicose vein group itself based on regional differences, by classifying the varicose tissues into tortuous and non-tortuous segments.

Topics: Blotting, Western; Female; Humans; Immunohistochemistry; Male; Muscle, Smooth, Vascular; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Transforming Growth Factor beta; Up-Regulation; Varicose Veins

This study evaluates possible changes in the synthesis/degradation of elastic components of the vein wall in an attempt to explain the development of varicosis. Healthy and varicose saphenous veins were subjected to immunohistochemical analysis using anti-elastin, anti-fibrillin-1, anti-elastase, anti-transforming growth factor (TGF)-beta and anti-latent TGFbeta binding protein (LTBP)-2 monoclonal antibodies. In situ hybridization was performed using specific probes for tropoelastin and fibrillin-1. In healthy veins, elastin and fibrillin-1 showed even, overlapping distribution patterns indicating their particular abundance in the adventitia and at the intima/media interface. The expression of tropoelastin and fibrillin-1 was high in smooth muscle cells bordering the elastic laminae. Elastin, fibrillin-1, and cells expressing fibrillin-1 and tropoelastin mRNA showed a patchy disorganized pattern, particularly in the proximal varicose segments of patients under 50 years of age. Enhanced elastase activity was noted in both control and varicose specimens from elderly subjects. Varicose veins specimens showed greater LTBP-2 and TGF expression. Both molecules were detected in the subendothelium and the media, particularly in areas of marked injury. Our findings suggest that the development of the varicose condition involves a restructuring of the elastic component of the vein wall, perhaps as a consequence of changes in the transcription mechanisms of muscle layer cells.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Carrier Proteins; Elastin; Extracellular Matrix; Humans; Immunohistochemistry; In Situ Hybridization; Latent TGF-beta Binding Proteins; Middle Aged; Muscle, Smooth, Vascular; Saphenous Vein; Transforming Growth Factor beta; Varicose Veins