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La Jolla Visitor Guide. Best of La Jolla Readers Poll. Contact Us. Find a Copy. Facebook Twitter Show more sharing options Share Close extra sharing options. Sponsored Columnists. Other studies showed that the medial layer consisted of increased number of collagen fibres and that elastin fibres are constantly fragmented with paralleled interruption of the internal elastic lamina.
The adventitial layer showed decreased density and size of elastin fibres and increased fibre degradation [ , ]. Several of the changes observed in connective tissue are thought to reflect variations in the levels of MMPs, the enzymes involved in regulating and maintaining the extracellular matrix that degrade extracellular matrix molecules, proteoglycans, elastin, and different types of collagens [ ].
Biochemical studies have also demonstrated a decrease in the elastin content of the affected vein wall [ ]. Pascual et al. LOXL1 is a cross-linking enzyme responsible for elastin polymer deposition. These events could reduce spontaneous reticulation of elastin and the partial loss of tissue elasticity in this group of patients [ ]. Collagen dysregulation in varicose veins have also been the subject of several studies.
Collagen type I mRNA expression and protein synthesis are increased in tissue media of varicose veins due to gene overexpression [ , ]. This imbalance between the synthesis of collagen type I and collagen type III could explain the lack of elasticity of varicose veins [ ].
In a recent investigation that examined the link between the loss of ECM and the biophysical properties of varicose veins, Jeanneret and colleagues identified that adventitial elastin and intimal type III collagen were specifically and differentially affected. The selective loss of these two elastic structural proteins can explain two biophysical properties of the vein wall.
Venous adventitial elastin has a critical role in regulating the venous diameter at rest, and, therefore, elastin loss may be a key factor in the development of varicose veins, preceding and precipitating dilatation. The concomitant reduction in intimal type III collagen is involved in abnormal distensibility [ ]. The relation between venous stretch and MMP expression in the wall of varicose veins has been extensively investigated.
In a series of studies to clarify the relationship between MMP and vein wall dilatation, Raffetto et al. Another study from the same group was performed in rat IVC to test the hypothesis that prolonged increases in vein wall tension cause overexpression of MMPs and decreased contractility, which in turn promotes venous dilation.
The results demonstrated that increases in magnitude and duration of wall tension were associated with reduced contraction and overexpression of MMP-2 and MMP There was a direct correlation between the expression of MMP-2 and MMP-9 and decreased vein contractile function [ ]. This study elucidated the mechanism and relation of HIFs and MMPs indicating that increased vein wall tension induces HIFs overexpression and causes an increase in MMPs expression and reduction of venous contraction, leading to progressive venous dilation which may contribute to varicose vein formation Figure 3 [ 91 ].
Jacob et al. Histological examination revealed disruption of elastic lamellae and a significantly high degree of loss of vascular SMCs [ 81 ]. The pathobiology of varicose vein formation is one of the fields that need increasing research attention given the significant social, medical, and economic importance.
The recent characterization of several mechanosensors in the ECs and SMCs will stimulate future research of the mechanotransduction signaling pathways involved in the development of varicose veins.
Possible areas of future research and intervention could be suggested based on current understanding of mechanotransduction. One such research areas would investigate stretch-induced myogenic response in human saphenous vein. Given that studies have shown that saphenous vein of humans and animals exhibits an active myogenic response and that stretch-induced AT1R and TRPC channels signaling mechanism are responsible for the myogenic response in arteries, it remains, however, to delineate the underlying signaling pathways and the identity of mechanosensors of myogenic response in human superficial veins of the lower extremities.
Failure of this myogenic response may have a critical role in the development of varicose veins. This would explain the greater incidence of varicose veins in females. These and other studies would expand our understanding on how vein wall ECs, SMCs, FBs, and ECM sense and transduce stimuli of hemodynamic forces, particularly venous hypertension, into biochemical signals. This knowledge would be critical to developing new therapies for the prevention and treatment of varicose veins.
The author would like to thank Professor Raouf Khalil, Brigham and Women's Hospital, Harvard Medical School, for his valuable discussion during the preparation of this paper. National Center for Biotechnology Information , U. Int J Vasc Med.
Published online Feb Hussein M. Author information Article notes Copyright and License information Disclaimer. Atta: moc. Received Sep 30; Accepted Nov This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This article has been cited by other articles in PMC. Abstract Varicose veins affect approximately one-third of the adult population and result in significant psychological, physical, and financial burden.
Introduction Varicose veins are a common venous disease of the lower extremity which affects more than 30 per cent of the adult population in Western countries [ 1 — 3 ]. Open in a separate window. Figure 1. Mechanotransduction of Venous Hypertension Blood vessels are constantly subjected to various types of hemodynamic forces including shear stress and circumferential stretch induced by the blood flow and pressure, respectively.
Mechanotransduction of Circumferential Stretch Elevated venous pressure in the lower extremity veins during prolonged standing generates circumferential stretch of the vein wall and imposes mechanical stimulation on both ECs and SMCs.
Figure 2. Integrins Integrins are a large family of cell surface receptors that provide adhesion of cells to both the extracellular matrix ECM and neighboring cells. Flow-Sensitive Ion Channels Activation of flow-sensitive ion channels is one of the most rapid EC responses to flow [ 25 ]. Stretch Signaling Pathways in Varicose Veins Although the link between mechanosensors translation of circumferential stretch to biological molecules remains to be fully elucidated, considerable knowledge of downstream signaling pathways has been gained.
Figure 3. Stretch-Induced Hypoxia Hypoxia of the lower extremity vein wall has been proposed as a causative factor in varicose vein formation [ 74 — 76 ]. Stretch-Induced Inflammation Evidence has accumulated to support the role of venous hypertension and shear stress in the development of inflammation both of the wall of the veins and in the surrounding dermal and subdermal tissues [ 92 ].
Stretch-Induced Vein Wall Remodeling 8. Role of Collagen and Elastin Several studies demonstrated that there is significant hypertrophy of the media layer of the wall of varicose veins compared with normal veins [ ].
Conclusions and Perspectives The pathobiology of varicose vein formation is one of the fields that need increasing research attention given the significant social, medical, and economic importance. Acknowledgment The author would like to thank Professor Raouf Khalil, Brigham and Women's Hospital, Harvard Medical School, for his valuable discussion during the preparation of this paper.
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Integrin regulation. A blood clot in the lungs is very serious and may cause death. Symptoms include chest pain, trouble breathing, coughing may cough up blood , a fast heartbeat, sweating, and fainting.
If you have symptoms that may mean a blood clot in the lungs, call or get emergency help. The following are the most common symptoms of varicose veins. However, each individual may experience symptoms differently.
Symptoms may include:. Severe varicose veins may eventually produce long-term mild swelling that can result in more serious skin and tissue problems. These include ulcers and nonhealing sores. The symptoms of varicose veins may resemble other medical conditions or problems. Always talk with your healthcare provider for a diagnosis. In addition to a complete medical history and physical exam, diagnostic procedures for varicose veins may include:.
Duplex ultrasound. A type of vascular ultrasound done to check blood flow and the structure of the leg veins. Duplex means two types of ultrasound are used. Medical treatment may not be necessary if there are no symptoms. However, varicose veins may sometimes worsen without treatment. Elevation of the legs.
You may be instructed to elevate your feet above the level of your heart 3 or 4 times a day for about 15 minutes at a time. If you need to sit or stand for a long period of time, flexing bending your legs occasionally can help keep blood circulating.
If you have mild to moderate varicose veins, elevating your legs can help reduce leg swelling and relieve other symptoms. Compression stockings. These elastic stockings squeeze the veins and prevent blood from pooling. Compression stockings can be effective if they are worn every day. Sclerotherapy is the most common treatment for both spider and varicose veins. A salt saline or chemical solution is injected into the varicose veins.
They no longer carry blood.
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