Chronic Venous Insufficiency and Biochemical Persperctive On Pharmacological Therapy
Özet
This text explores Chronic Venous Insufficiency (CVI) and its pharmacological treatments from a biochemical perspective. CVI is a widespread socio-economic problem characterized by valvular incompetence in lower extremity veins, leading to blood reflux, increased hydrostatic pressure, and tissue edema. Key risk factors include age, family history, gender, obesity, and prolonged standing. Pathophysiologically, the disease triggers severe inflammation driven by low shear stress, hypoxia, and endothelial dysfunction, accompanied by significant changes in the extracellular matrix, such as elastin degradation and matrix metalloproteinase (MMP) instability. While non-pharmacological approaches like compression stockings or ablative surgery are standard, pharmacological interventions rely on venoactive and diuretic drugs to alleviate pain and edema. Natural venoactives include Micronized Purified Flavonoid Fraction (MPFF), benzopyrones, and saponosides, which reduce leukocyte adhesion, suppress cytokines like TNF-a and IL-6, and promote vascular healing. Synthetic agents like Calcium Dobesilate boost nitric oxide-synthase activity, while Sulodexide, a glycosaminoglycan mixture, limits the deleterious proteolytic cascade by inhibiting MMP secretion. Ultimately, clarifying the precise biochemical pathways of these agents remains crucial for establishing a definitive cure for CVI.
Referanslar
Beebe-Dimmer, J.L., Pfeifer, J.R., Engle, J.S. The epidemiology of chronic venous insufficiency and varicose veins. Annals of Epidemiology, 2005; 15 (3), 175-184.
Rabe, E., Pannier, F. (2017). Epidemiology of chronic venous disorders. Peter Gloviczki (Ed.), Handbook of Venous and Lymphatic Disorders in (p. 121-128). USA: CRC Press.
Robertson, L., Evans, C., Fowkes, F.G. Epidemiology of chronic venous disease. Phlebology, 2008; 23 (3), 103-111.
Grand Wiew Research (2019). Varicose Veins Treatment Devices Market Size, Share & Trends Analysis Report By Type (Endovenous Ablation, Sclerotherapy, Surgical Ligation & Stripping), By Region, And Segment Forecasts, 2019 – 2025. (Accessed at 22/06/2021, https://www.grandviewresearch.com/industry-analysis/varicose-veins-treatment-devices-market)
Yılmaz, S. Venöz Yetmezlik ve Varis Tedavisinde Güncel Yaklaşımlar. Klinik Gelişim, 2010; 23, 57-62.
Nguyen, T.H. Evaluation of venousinsufficiency. Semin Cutan Med Surg., 2005; 24, 162-174
Joseph N.B.A., FaizanThouseef, M., Devi, M.U. A multicenter review of epidemiology and management of varicose veins for national guidance. Annals of Medicine and Surgery, 2016; 8, 21–27.
Hanrahan, L.M., Kechejian, G.J., Cordts, P.R. Patterns of venous insufficiency in patients with varicose veins. Archives of Surgery, 1991; 126 (6), 687-690.
Meissner, M.H., Gloviczki, P., Bergan, J. Primary chronic venous disorders. Journal of Vascular Surgery, 2007; 46 (Suppl), 54-67.
Beebe-Dimmer, J.L., Pfeifer, J.R., Engle, J.S. The epidemiology of chronic venous insufficiency and varicose veins. Annals of Epidemiology, 2005; 15 (3), 175-184.
Scherger, J. Varicose veins. Vice President for Primary Care. 2012;1-67.
Ascher, E., Jacob, T., Hingorani, A. Expression of molecular mediators of apoptosis and their role in the pathogenesis of lower-extremity varicose veins. Journal of vasculer Surgery, 2001; 33 (5), 1080-1086.
Naoum, J.J., Hunter, G.C., Woodside, K.J. Current Advances in the Pathogenesis of Varicose Veins. Journal of Surgical Research, 2007; 141 (2), 311–316.
Sayın, A., Dayıoğlu, E. Kronik venöz yetersizlikte klinik ve CEAP Sınıflaması. İ.Ü. Cerrahpaşa Tıp Fakültesi Sürekli Tıp Eğitimi Etkinlikleri Sempozyum Dizisi, 2007; 56, 39-46.
Köksal, C., Alsalehi, S., Kocamaz, Ö. Treatment of Chronic Venous Insufficiency (Kronik venöz yetmezlik tedavisi). Kosuyolu Heart J., 2010; 13 (2), 28-33.
Beale, R.J., Gough, M.J. Treatment options for primary varicose veins--a review. Eur J Vasc Endovasc Surg. 2005; 30 (1), 83-95.
Bozkurt, K., Demirkılıç, U., Topcuoğlu, Ş. (2008). Türk Kalp Damar Cerrahisi Derneği Periferik Arter ve Ven Hastalıkları Tedavi Klavuzu. Ankara: Öncü Basımevi.
Venturi, M., Bonavina, L., Annoni, F. Biochemical assay of collagen and elastin in the normal and varicose vein wall. Journal of Surgical Research, 1996; 60 (1), 245-248.
Aunapuu, M., Arend, A. Histopathological changes and expression of adhesion molecules and laminin in varicose veins. Vasa, 2005; 34 (3), 170-175.
Kockx, M.M., Knaapen, M.W., Bortier, H.E. Vascular remodeling in varicose veins. Angiology, 1998; 49 (11), 871-877.
Sorescu, G.P., Song, H., Tressel, S.L. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a nox1 based NADPH oxidase. Circulation Research, 2004; 95 (8), 773-779.
Scheller, J., Chalaris, A., Schmidt-Arras, D. The pro and anti-inflammatory properties of thecytokine interleukin-6. Biochimica et Biophysica Acta (BBA) Molecular Cell Research, 2011; 1813 (5), 878-888.
Yasim, A., Kilinc, M.¸ Aral, M. Serum concentration of procoagulant, endothelial and oxidative stress markers in early primary varicose veins. Phlebology, 2008; 23 (1), 15–20.
Poredos, P., Spirkoska, A., Rucigaj, T. Do Blood Constituents in Varicose Veins Differ From the Systemic Blood Constituents? European Journal of Vascular and Endovascular Surgery, 2015; 50 (2), 250-256.
Castro-Ferreira, R., Cardoso, R., Leite-Moreira, A. The role of endothelial dysfunction and inflammation in chronic venous disease. Annals of Vascular Surgery, 2018; 46, 380–393.
Lim, C.S., Davies, A.H. Pathogenesis of primary varicose veins. British Journal of Surgery, 2009; 96 (11), 1231–1242.
Lim, C.S., Shalhoub, J., Gohel, M.S. Matrix metalloproteinases in vascular disease – a potential therapeutic target? Current Vascular Pharmacology, 2010; 8 (1),75-85.
Tiwary, S.K., Kumar, A., Mishra, S.P. Study of association of varicose veins and inflammation by inflammatory markers. Phlebology, 2020; 35 (9), 679–685.
Somers, P., Knaapen, M. The histopathology of varicose vein disease. Angiology, 2006; 57, 546-555.
Foudi, N., Gomez, I., Benyahia, C. Prostaglandin E2 receptor subtypes in human blood and vascular cells. European Journal of Pharmacology, 2012; 695 (1-3),1-6.
Damnjanovic, I., Stefanovic, N., Zlatkovic-Guberinic, S. Self Medication Practices among the patients with Chronic Venous Disease. Farmacia, 2020; 68 (2), 225-231
Belczak, S.Q., Sincos, I.R., Campos, W. Veno-active drugs for chronic venous disease: A randomized, double-blinf, placebo-controlled parallel-design trial. Phlebology, 2014; 29 (7), 454-460.
Ramelet, A.A., Boisseau, M.R., Allegra, C. Veno-active drugs in the management of chronic venous disease. An international consensus statement: current medical position, prospective views and final resolution. Clin Hemorheol Microcirc., 2005; 33 (4), 309-319.
Katsenis, K. Micronized purified flavonoid fraction (MPFF): A review of its pharmacological effects, therapeutic efficacy and benefits in the management of chronic venous insufficiency. Current Vascular Pharmacology, 2005; 3 (1), 1-9.
Bush, R., Comerota, A., Meissner, M. Recommendations for the medical management of chronic venous disease: The role of Micronized Purified Flavanoid Fraction (MPFF). Phlebology, 2017; 32(1_suppl), 3-19
Shoab, S.S., Porter, J.B., Scurr, J.H. Effect of oral micronized purified flavonoid fraction treatment on leukocyte adhesion molecule expression in patients with chronic venous disease: A pilot study. Journal of Vascular Surgery, 2000; 31 (3), 456-461.
Shoab, S.S., Scurr, J.H., Coleridge Smith, P.D. Plasma VGEF during oral therapy in patients with chronic venous disease with purified micronized fraction. A pilot study. European Journal of Vascular and Endovascular Surgery, 1999; 18 (4), 334-348.
Zheng, Y., Zhang, R., Shi, W. Metabolism and pharmacological activities of the natural health-benefiting compound diosmin. Food & Function, 2020; 11 (10), 8472-8492.
Feldo, M., Wójciak-Kosior, M., Sowa, I. Effect of Diosmin Administration in Patients with Chronic Venous Disorders on Selected Factors Affecting Angiogenesis. Molecules, 2019; 24 (18), 3316-3327.
Smetanina, M.A., Shevela, A.I., Gavrilov, K.A. The genetic constituent of varicose vein pathogenesis as a key for future treatment option development. Vessel Plus, 2021; 5 (19), 1-13.
Pietrzycka, A., Kózka, M., Urbanek, T. Effect of Micronized Purified Flavonoid Fraction Therapy on Endothelin-1 and TNF-α Levels in Relation to Antioxidant Enzyme Balance in the Peripheral Blood of Women with Varicose Veins. Current Vascular Pharmacology, 2015; 13 (6), 801-808.
Kauss, T., Moynet, D., Rambert, J. Rutoside decreases human macrophage-derived inflammatory mediators and improves clinical signs in adjuvant-induced arthritis. Arthritis Research & Therapy, 2008; 10 (1), 1-9.
Nikfarjam, B.A., Adineh, M., Hajiali, F. Treatment with Rutin—A Therapeutic Strategy for Neutrophil-Mediated Inflammatory and Autoimmune Diseases—Anti-inflammatory Effects of Rutin on Neutrophils. Journal of Pharmacopuncture, 2017; 20 (1), 52–56.
Benarroch, I.S., Brodsky, M., Rubinstein, A. Treatment of blood hyperviscosity with calcium dobesilate in patients with diabetic retinopathy. Ophthalmic Research, 1985; 17 (3), 131–138.
Suschek, C., Kolb, H., Kolb-Bachofen, V. Dobesilate enhances endothelial nitricoxide synthase-activity in macro- and microvascular endothelial cells. British Journal of Pharmacology, 1997; 122 (7), 1502–1508.
Coccheri, S., Mannello, F. Development and use of sulodexide in vascular diseases: Implications for treatment. Drug Design, Development and Therapy, 2014; 24 (8), 49–65.
Mannello, F., Medda, V., Ligi, D. Glycosaminoglycan sulodexide inhibition of MMP-9 gelatinase secretion and activity: Possible pharmacological role against collagen degradation in vascular chronic diseases. Current Vascular Pharmacology, 2013; 11 (3), 354–365.
Ligi, D., Mosti, G., Croce, L. Chronic venous disease—Part II: Proteolytic biomarkers in wound healing. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2016; 1862 (10), 1900-1908.
Midgett, C., Stitham, J., Martin, K. Prostacyclin receptor regulation -- from transcription to trafficking. Current Molecular Medicine, 2011; 11: (7), 517-528.
Alphonsus, C.S., Rodseth, R.N. The endothelial glycocalyx: A review of the vascular barrier. Anaesthesia, 2014; 69 (7), 777–784.
Gschwandtner, M., Strutzmann, E., Teixeira, M.M. Glycosaminoglycans are important mediators of neutrophilic inflammation in vivo. Cytokine, 2017; 91, 65–73.
