title: Increased RhoA/Rho-Kinase Activity and Markers of Endothelial Dysfunction in Young Adult Subjects with Metabolic Syndrome.
abstract: BACKGROUND
  Metabolic syndrome, a chronic condition associated with higher risk of cardiovascular diseases, is increasingly prevalent in young adults. Dyslipidemia, proinflammatory cytokines, endothelial dysfunction signs, and RhoA/Rho-kinase (ROCK) activation are considered risk factors of cardiovascular diseases. The occurrence of these factors in young patients with metabolic syndrome but without type 2 diabetes or hypertension has not been fully studied. The objective of this study was to evaluate young subjects with enlarged waist circumference and dyslipidemia but without type 2 diabetes or hypertension,for markers associated with a higher risk of cardiovascular diseases.
  
  
  METHODS
  Thirty-two male patients aged 31 ± 1.3 years diagnosed with metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III guide for enlarged waist circumference, elevated triglycerides, and low HDL levels, but with blood pressure and fasting glucose within normal ranges, were evaluated for RhoA/ROCK activity in leukocytes, serum fatty acid methyl esters profile, proinflammatory cytokines, and oxidative stress markers in addition to thrombin generation and biochemical analysis. Age- and gender-matched healthy subjects were equivalently evaluated.
  
  
  RESULTS
  Patients showed higher RhoA/ROCK activity, elevated levels of interleukin-6, soluble CD40L, monocyte chemoattractant protein, and high-sensitivity C-reactive protein (P < 0.001) as well as parameters of endogenous thrombin generation potential (P < 0.05) compared with healthy subjects. Increased thiobarbituric acid reactive substances, advanced oxidation protein product, and insulin levels and low nitric oxide biodisponibility (P < 0.001) were also found in patients as compared with controls. Palmitic acid was one of the saturated fatty acids found to be significantly elevated in patients compared with control subjects (P = 0.0087).
  
  
  CONCLUSIONS
  Increased markers of cardiovascular risk are already present in young adults with metabolic syndrome but without type 2 diabetes or hypertension.
authors.affiliation: 1 Department of Hematology and Oncology, School of Medicine, Pontificia Universidad Católica de Chile , Santiago, Chile .
authors.forename: Alberto
authors.initials: A
authors.lastname: Leguina-Ruzzi
authors.affiliation: 1 Department of Hematology and Oncology, School of Medicine, Pontificia Universidad Católica de Chile , Santiago, Chile .
authors.forename: Jaime
authors.initials: J
authors.lastname: Pereira
authors.affiliation: 1 Department of Hematology and Oncology, School of Medicine, Pontificia Universidad Católica de Chile , Santiago, Chile .
authors.forename: Karla
authors.initials: K
authors.lastname: Pereira-Flores
authors.affiliation: 2 Departamento de Ciencias Médicas, Facultad de Medicina Odontología, Universidad de Antofagasta , Chile .
authors.forename: Juan P
authors.initials: JP
authors.lastname: Valderas
authors.affiliation: 1 Department of Hematology and Oncology, School of Medicine, Pontificia Universidad Católica de Chile , Santiago, Chile .
authors.forename: Diego
authors.initials: D
authors.lastname: Mezzano
authors.affiliation: 3 Department of Physiology, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile , Santiago, Chile .
authors.forename: Victoria
authors.initials: V
authors.lastname: Velarde
authors.affiliation: 1 Department of Hematology and Oncology, School of Medicine, Pontificia Universidad Católica de Chile , Santiago, Chile .
authors.forename: Claudia G
authors.initials: CG
authors.lastname: Sáez
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology; D050177:Overweight / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology; D018384:Oxidative Stress; D019308:Palmitic Acid / Q000097:blood; D011379:Prognosis; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference; D055815:Young Adult; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D018836:Inflammation Mediators; D014280:Triglycerides; C066737:RHOA protein, human; D019308:Palmitic Acid; D054460:rho-Associated Kinases; D013917:Thrombin; D020742:rhoA GTP-Binding Protein