title: Smoking and Female Sex: Independent Predictors of Human Vascular Smooth Muscle Cells Stiffening.
abstract: OBJECTIVE
  Recent evidence shows the rigidity of vascular smooth muscle cells (VSMC) contributes to vascular mechanics. Arterial rigidity is an independent cardiovascular risk factor whose associated modifications in VSMC viscoelasticity have never been investigated. This study's objective was to evaluate if the arterial rigidity risk factors aging, African ancestry, female sex, smoking and diabetes mellitus are associated with VMSC stiffening in an experimental model using a human derived vascular smooth muscle primary cell line repository.
  
  
  METHODS
  Eighty patients subjected to coronary artery bypass surgery were enrolled. VSMCs were extracted from internal thoracic artery fragments and mechanically evaluated using Optical Magnetic Twisting Cytometry assay. The obtained mechanical variables were correlated with the clinical variables: age, gender, African ancestry, smoking and diabetes mellitus.
  
  
  RESULTS
  The mechanical variables Gr, G'r and G"r had a normal distribution, demonstrating an inter-individual variability of VSMC viscoelasticity, which has never been reported before. Female sex and smoking were independently associated with VSMC stiffening: Gr (apparent cell stiffness) p = 0.022 and p = 0.018, R2 0.164; G'r (elastic modulus) p = 0.019 and p = 0.009, R2 0.184 and G"r (dissipative modulus) p = 0.011 and p = 0.66, R2 0.141.
  
  
  CONCLUSIONS
  Female sex and smoking are independent predictors of VSMC stiffening. This pro-rigidity effect represents an important element for understanding the vascular rigidity observed in post-menopausal females and smokers, as well as a potential therapeutic target to be explored in the future. There is a significant inter-individual variation of VSMC viscoelasticity, which is slightly modulated by clinical variables and probably relies on molecular factors.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Carla Luana
authors.initials: CL
authors.lastname: Dinardo
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Hadassa Campos
authors.initials: HC
authors.lastname: Santos
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: André Ramos
authors.initials: AR
authors.lastname: Vaquero
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: André Ricardo
authors.initials: AR
authors.lastname: Martelini
authors.affiliation: Coronary Surgery Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Luis Alberto Oliveira
authors.initials: LA
authors.lastname: Dallan
authors.affiliation: Laboratory of Microrheology and Molecular Physiology, Physics Institute, University of São Paulo, São Paulo, Brazil.
authors.forename: Adriano Mesquita
authors.initials: AM
authors.lastname: Alencar
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
mesh_terms: D000367:Age Factors; D000368:Aged; D044383:Black People; D002318:Cardiovascular Diseases / Q000473:pathology / Q000601:surgery; D002478:Cells, Cultured; D001026:Coronary Artery Bypass; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D055119:Elastic Modulus; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D017698:Postmenopause; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking