title: Quantitative proteomics analysis of varicose veins: identification of a set of differentially expressed proteins related to ATP generation and utilization.
abstract: Although morphological and anatomical studies indicate that varicose veins are characterized by venous wall weakening and subendothelial fibrosis, the exact underlying biochemical mechanism of their development remains unknown. Additionally, no quantitative proteomic study of venous proteins leading to decreased contractility of varicose veins has been reported to date. Therefore, to elucidate the molecular mechanism of altered vascular contractility, this study performed shotgun proteomic analysis to obtain protein expression profiles in patients with varicose veins. Stable isotope dimethyl labeling coupled with nanoLC-MS/MS revealed downregulation in 12 polypeptides, including myosin light chain kinase, creatine kinase B-type, ATP synthase, phosphoglycerate kinase, and pyruvate kinase. However, analyses of protein species associated with cytoskeletal assembly or with cellular morphology showed no clear up- or down-regulation. These results indicate that defects in ATP generation and utilization may account for the dysfunction of vascular smooth muscle following formation of varicose veins. Collectively, the severity of varicose veins depends on the regulatory roles of various protein factors in the metabolic coordination of physiological functions. This pilot study improves understanding of the pathogenesis of varicose veins and lays the foundation for further validation and clinical translation of biomarkers for targeted therapies in treating this disease.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Research Resources and Development, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chao-Jen
authors.initials: CJ
authors.lastname: Kuo
authors.forename: Shih-Shin
authors.initials: SS
authors.lastname: Liang
authors.forename: Edward
authors.initials: E
authors.lastname: Hsi
authors.forename: Shyh-Horng
authors.initials: SH
authors.lastname: Chiou
authors.forename: Sin-Daw
authors.initials: SD
authors.lastname: Lin
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000378:metabolism; D000595:Amino Acid Sequence; D002853:Chromatography, Liquid; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D014648:Varicose Veins / Q000378:metabolism*
chemical_list: D011506:Proteins; D000255:Adenosine Triphosphate
keywords: NanoLC-MS/MS; Quantitative proteomics; Shotgun analysis; Stable isotope dimethyl labeling; Varicose veins