Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3825_Библиотеки_им_академика_М_И_Перельмана

of defects in vascular remodeling [29]. Region near rs3101725 contains two genes, SLC12A2 and FBN2, which are possibly involved in varicose transformation. Potassium voltage-gated channels, which are encoded by KCNJ16 and KCNJ2 genes tagged by rs236530, also may have a role in vascular biology which is largely unknown. COL2A1 gene is under direct control of the SOX9 gene product and encodes an extracellular matrix component whose transcription is regulated by RAPGEF3 gene in the rs73107980 locus. RAPGEF3 gene also regulates vascular permeability and further promotes vascular smooth muscle cell migration (Fig.14.4) [27]. Finan etal. [30] placed SLC12A2, FBN2, STIM2, HFE, KCNJ16, KCNJ2, and COL2A1 genes in the category of druggable gene set, whereas PIEZO1 and the KCNJ2 gene products into the “potential drug target” class as according to the Human Protein Atlas (https://www.proteinatlas.org/) [30, 31]. The underlying effect of the plasma level of MHC class I polypeptide-related sequence B protein (MICB) and CD209 antigen was assessed by Mendelian randomization analysis. MICB, a ligand for activation of NKG2D receptor present on natural killer and other immune­related cells and CD209 (DC-SIGN), is a C-type lectin receptor expressed on den­dritic cells and macrophages. Hence, both of them are implicated in innate and adaptive immune response. VVs is associated with ABO gene polymorphism as well as blood group A which is facilitated by CD209 protein [27].

that MMPs are highly implicated in the pathogenesis of CVD; they cause degrada­tion of extracellular membrane leading to venous remodeling, structural wall change, and subsequently venous dilation and valve dysfunction (Fig.14.5) [47]. MMPs regulate or degrade the extracellular membrane through hydrolysis, and TIMPs are the tissue inhibitors of MMPs that have an effect on vascular remodeling. Therefore, the balance between two may cause vessel wall anomalies, eventually vascular disease such as varicosity and ulceration [48]. The dysregulation of MMP and TIMP activity causes impaired ulcer healing. According to Saito etal. [49], pro­ulcer condition is caused due to elevated MMP-2 level which affects tissue remodel­ing [49]. In fact, Herouy etal. (2001) found increased MMP-1, -22, and -213 and decreased TIMP-1, -22in skin lesions while observing stasis dermatitis which is the result of impaired venous drainage described by dermal neovascularization [50]. Subsequently, Xu etal. [48], demonstrated that MMP-9 and TIMP2 gene polymor­phisms impose higher risk to the patients for developing VVs [48]. Deatrick etal. (2011) found that after 6months of vein remodeling an acute DVT was associated with MMP-9, which is precisely associated with resolution and prediction of PTS [51]. In acute DVT, there was increased MMP-9 and decreased Toll-like receptor 9 expression. Deatrick etal. [52] studied mouse model and found that MMP-9 modu­lates collagen content in the vein wall which also promotes inammation and bro­sis, thus marking it as a potent target to decrease the brotic complications of PTS [52]. In addition, Beidler et al. [53] demonstrated that all the MMPs (except MMP-7), mainly MMP-8 and MMP-9, were highly expressed in venous leg ulcers [53]. In fact, Singh etal. in 2010 identied MMP-12 gene polymorphisms among numbers of SNPs associated with venous leg ulcers to have function in development